IP Library Granted Patent US 12,239,126
Granted Patent B2
US 12,239,126 · App. 16/705,966 · Granted Mar 4, 2025

Methods and compositions for preserving tissues and organs

Inventors: Martin L. Yarmush (Newton, MA); Mehmet Toner (Wellesley, MA); Maria-Louisa Izamis (Boston, MA); Timothy Antonie Berendsen (Melrose, MA); Robert Marius Bieganski (Cambridge, MA); Osman Berk Usta (Watertown, MA); Basak Elif Uygun (Newton, MA); Mustafa Korkut Uygun (Newton, MA); Sinem Perk (Chicago, IL)
Assignee: The General Hospital Corporation
A01N1/0226G01N33/5091G01N1/42
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,239,126
App. No.
16/705,966
Granted
Mar 4, 2025
Kind
B2
Abstract

The present invention generally relates to methods and compositions to determine viability of an organ for transplantation and other medical purposes. One aspect of the invention relates to a method for assessing the viability of an organ by measuring the energy parameters to determine the energy level of the organ by determining the stored cellular energy (e.g., ATP levels), and/or energy consumption over a particular time period of viability. The energy parameters can be compared to reference energy parameters as a highly accurate and reliable prediction of viable cell yield, and organ viability. Another aspect of the invention relates methods to preserve or extend the time period of viability of an organ any combination of (i) preservation perfusion of the organ to prevent ischemic damage, (ii) chemical metabolic suppression of the organ e.g., using metabolic suppressants, (iii) metabolic suppression by physical or environmental conditions, e.g., sub-zero non-freezing storage.

Claims (15)

1. A method for extending the viable preservation of a harvested organ for transplantation, the method comprising:

contacting at least a portion of the harvested organ with a preservation perfusion solution, wherein the preservation perfusion solution comprises (i) at least 3 of the following: insulin, L-glutamine, hydrocortisone, heparin, penicillin, streptomycin sulfate, and adenosine, and (ii) a PPARγ ligand selected from the group consisting of troglitazone and rosiglitazone, or derivatives thereof,

wherein the harvested organ is a liver, pancreas, kidney, spleen, or lung.

2. The method of claim 1 , wherein the preservation perfusion solution does not comprise erythrocytes.

3. The method of claim 1 , wherein contacting at least a portion of the harvested organ with the preservation perfusion solution comprises immersing, partially or completely, the harvested organ with the preservation perfusion solution.

4. The method of claim 1 , wherein contacting at least a portion of the harvested organ with the preservation perfusion solution comprises perfusing the harvested organ with the preservation perfusion solution.

5. The method of claim 1 , wherein the harvested organ has ischemic damage.

6. The method of claim 1 , wherein the harvested organ is cooled and stored at a predetermined sub-zero temperature without freezing.

7. The method of claim 5 , wherein the harvested organ is contacted with a media comprising a supercoolant agent prior to cooling and freezing.

8. The method of claim 7 , wherein the supercoolant agent is selected from the group consisting of: 3-O-methyl-glucose (30 MG), hypothermosol, trehalose, polyvinyl alcohol, polyvinylpyrrolidone, DMSO, polygylcerol, K3Glc (Kaempferol 3-O-β-D-glucopyranoside); K7Glc (Kaempferol 7-O-β-D-glucopyranoside), Q7Glc (Quercetin 7-O-β-D-glucopyranoside), Q3Ga1 (Quercetin 3-O-β-D-galactopyranoside), and polyethylene glycol.

9. The method of claim 8 , wherein the supercoolant agent is 3-O-methyl-glucose (30 MG).

10. A method for extending the viable preservation of a harvested organ, the method comprising:

contacting at least a portion of the harvested organ with a first preservation perfusion solution, wherein the first preservation perfusion solution comprises at least 3 of the following: insulin, L-glutamine, hydrocortisone, heparin, penicillin, streptomycin sulfate, and adenosine; and

contacting at least a portion of the harvested organ with a second preservation solution comprising a PPARγ ligand selected from the group consisting of troglitazone and rosiglitazone, or derivatives thereof,

wherein the harvested organ is a liver, pancreas, kidney, spleen, or lung.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2020
From: TONER, MEHMET; USTA, OSMAN BERK
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 052426/0470 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2020
From: PERK, SINEM
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 052426/0558 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2020
From: BIEGANSKI, ROBERT MARIUS
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 052426/0623 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2020
From: YARMUSH, MARTIN L.; IZAMIS, MARIA-LOUISA; BERENDSEN, TIM ANTONIE; UYGUN, BASAK ELIF; UYGUN, MUSTAFA KORKUT
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 052426/0836 →
Continuity (5)
Division 13695459
Provisional Application 61447905 · Mar 1, 2011
Provisional Application 61364186 · Jul 14, 2010
Provisional Application 61330959 · May 4, 2010
Related Publication 20200236924A1 · Jul 30, 2020
References Cited (400)
US 1682344A · Lesieur · 1928 [cited by applicant]
US 1916658A · Davidson · 1933 [cited by applicant]
US 3183961A · Brandt · 1965 [cited by applicant]
US 3406531A · Swenson et al. · 1968 [cited by applicant]
US 3468136A · Swenson et al. · 1969 [cited by applicant]
US 3545221A · Swenson et al. · 1970 [cited by applicant]
US 3607646A · De Roissart · 1971 [cited by applicant]
US 3660241A · Michielsen · 1972 [cited by applicant]
US 3738914A · Knudson et al. · 1973 [cited by applicant]
US 3772153A · De Roissart · 1973 [cited by applicant]
US 3810367A · Peterson · 1974 [cited by applicant]
US 3843455A · Bier · 1974 [cited by applicant]
US 3877843A · Fischel · 1975 [cited by applicant]
US 3881990A · Burton et al. · 1975 [cited by applicant]
US 3914954A · Doerig · 1975 [cited by applicant]
US 3995444A · Clark et al. · 1976 [cited by applicant]
US 4186565A · Toledo-Pereyra · 1980 [cited by applicant]
US 4242883A · Toledo-Pereyra · 1981 [cited by applicant]
US 4745759A · Bauer et al. · 1988 [cited by applicant]
US 4798824A · Belzer et al. · 1989 [cited by applicant]
US 5356771A · O'Dell · 1994 [cited by applicant]
US 6020120A · Sharvata · 2000 [cited by applicant]
US 6046046A · Hassanein · 2000 [cited by applicant]
US 6524785B1 · Cozzone et al. · 2003 [cited by applicant]
US 6642045B1 · Brasile · 2003 [cited by applicant]
US 6942859B2 · Fisher et al. · 2005 [cited by applicant]
US 7410474B1 · Friend et al. · 2008 [cited by applicant]
US 7504201B2 · Taylor et al. · 2009 [cited by applicant]
US 7572622B2 · Hassanein et al. · 2009 [cited by applicant]
US 7651835B2 · Hassanein et al. · 2010 [cited by applicant]
US 7691622B2 · Garland et al. · 2010 [cited by applicant]
US 7749693B2 · Brassil et al. · 2010 [cited by applicant]
US 7811558B2 · Ho et al. · 2010 [cited by applicant]
US 7811808B2 · Van Der Plaats et al. · 2010 [cited by applicant]
US 7824848B2 · Owen et al. · 2010 [cited by applicant]
US 8268612B2 · Owen et al. · 2012 [cited by applicant]
US 8287580B2 · Rakhorst et al. · 2012 [cited by applicant]
US 8323954B2 · Kravitz et al. · 2012 [cited by applicant]
US 8440390B2 · Brockbank · 2013 [cited by applicant]
US 8765364B2 · Curtis et al. · 2014 [cited by applicant]
US 8771930B2 · Curtis et al. · 2014 [cited by applicant]
US 8927257B2 · Hutzenlaub et al. · 2015 [cited by applicant]
US 8986978B2 · Brassil · 2015 [cited by applicant]
US 9078428B2 · Hassanein et al. · 2015 [cited by applicant]
US 9215867B2 · Hassanein et al. · 2015 [cited by applicant]
US 9247728B2 · Fishman et al. · 2016 [cited by applicant]
US 10750739B2 · Sandlin et al. · 2020 [cited by applicant]
US 20020039786A1 · Reid et al. · 2002 [cited by applicant]
US 20030216455A1 · Bril · 2003 [cited by examiner]
US 20040038997A1 · Macey · 2004 [cited by applicant]
US 20040058432A1 · Owen et al. · 2004 [cited by applicant]
US 20050147958A1 · Hassanein et al. · 2005 [cited by applicant]
US 20050214877A1 · Wyant et al. · 2005 [cited by applicant]
US 20050221269A1 · Taylor et al. · 2005 [cited by applicant]
US 20060011633A1 · Cook et al. · 2006 [cited by applicant]
US 20070009881A1 · Arzt et al. · 2007 [cited by applicant]
US 20070042339A1 · Toner et al. · 2007 [cited by applicant]
US 20070202485A1 · Nees · 2007 [cited by examiner]
US 20080096184A1 · Brasile · 2008 [cited by applicant]
US 20080234768A1 · Hassanein et al. · 2008 [cited by applicant]
US 20080288399A1 · Curtis et al. · 2008 [cited by applicant]
US 20090123437A1 · Takebe · 2009 [cited by applicant]
US 20100069326A1 · Haque et al. · 2010 [cited by applicant]
US 20110027771A1 · Deng · 2011 [cited by applicant]
US 20120201906A1 · Reynolds et al. · 2012 [cited by applicant]
US 20120251999A1 · Demirci et al. · 2012 [cited by applicant]
US 20140004046A1 · Raghunath et al. · 2014 [cited by applicant]
US 20150322404A1 · Yarmush et al. · 2015 [cited by applicant]
US 20170202211A1 · Muller et al. · 2017 [cited by applicant]
US 20180094232A1 · Toner et al. · 2018 [cited by applicant]
US 20190335745A1 · Fekete et al. · 2019 [cited by applicant]
US 20210007348A1 · Sandlin et al. · 2021 [cited by applicant]
US 20210100827A1 · Audia et al. · 2021 [cited by applicant]
US 20220104482A1 · Toner et al. · 2022 [cited by applicant]
US 20220330543A1 · Toner et al. · 2022 [cited by applicant]
CN 103827302A · 2014 [cited by applicant]
EP 1246903B1 · 2002 [cited by applicant]
JP 2004513369 · 2004 [cited by applicant]
JP 2008509924 · 2008 [cited by applicant]
JP 2009221128A · 2009 [cited by examiner]
JP 2012526849 · 2012 [cited by applicant]
KR 20010002227A · 2001 [cited by applicant]
WO WO1998041087 · 1998 [cited by applicant]
WO WO2002039124 · 2002 [cited by applicant]
WO WO2002049653 · 2002 [cited by applicant]
WO WO2006076401 · 2006 [cited by applicant]
WO 2007025233A1 · 2007 [cited by applicant]
WO WO2007120829 · 2007 [cited by applicant]
WO 2008024195A2 · 2008 [cited by applicant]
WO WO2011014741 · 2011 [cited by applicant]
WO WO2012024693 · 2012 [cited by applicant]
WO WO2013045458 · 2013 [cited by applicant]
WO WO2014059316 · 2014 [cited by applicant]
WO WO2017123759 · 2017 [cited by applicant]
WO WO2018232110 · 2018 [cited by applicant]
WO WO2020163500 · 2020 [cited by applicant]
WO WO2020229761 · 2020 [cited by applicant]
WO WO2022241417 · 2022 [cited by applicant]
Gary Lee et al., T0070907, a Selective Ligand for Peroxisome Proliferator-activated Receptor γ, Functions as an Antagonist of Biochemical and Cellular Activities, 2002, J.B.C., vol. 277, No. 22, pp. 19649-19657 (Year: 2… [cited by examiner]
Jill M. Seargent, Elisabeth A. Yates, Jason H. Gill, GW9662, a potent antagonist of PPARγ, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARγ agonist rosiglitazone, independently of … [cited by examiner]
Jen-Hwey Chiu, Juo-Chi Wang, Wing-Yiu Lui, Chew-Wun Wu, and Chuang-Ye Hong, Effect of Magnolol on in Vitro Mitochondrial Lipid Peroxidation and Isolated Cold-Preserved Warm-Reperfused Rat Livers, 1999, Journal of Surgic… [cited by examiner]
Sugimachi, K., Roach, K.L., Rhoads, D.B., Tompkins, R.G. & Toner, M. Nonmetabolizable glucose compounds impart cryotolerance to primary rat hepatocytes. Tissue Eng. 12, 579-588 (2006). (Year: 2006). [cited by examiner]
Tolboom et al., “Subnormothermic Machine Perfusion at Both 20° C. and 30° C. Recovers Ischemic Rat Livers for Successful Transplantation”, Journal of Surgical Research 175(1): 149-156 (2012). [cited by applicant]
Vairetti et al., “Correlation Between the Liver Temperature Employed During Machine Perfusion and Reperfusion Damage: Role of Ca2+”, Liver Transplantation 14:494-503 (2008). [cited by applicant]
Vajdova et al., “ATP-Supplies in the Cold-Preserved Liver: A Long-Neglected Factor of Organ Viability”, Hepatology 36(6):1543-1552 (2002). [cited by applicant]
Vajdova et al., “Cold-Preservation-Induced Sensitivity of Rat Hepatocyte Function to Rewarming Injury and Its Prevention by Short-Term Reperfusion”, Hepatology 32(2):289-296 (2000). [cited by applicant]
Van Der Plaats et al., “The Groningen Hypothermic Liver Perfusion Pump: Functional Evaluation of a New Machine Perfusion System”, Annals of Biomedical Engineering 34(12):1924-1934 (2006). [cited by applicant]
Vollmar et al., “In vivo quantification of ageing changes in the rat liver from early juvenile to senescent life”, Liver 2:330-341 (2002). [cited by applicant]
Wojcicki et al., “Biliary Tract Complications after Liver Transplantation: A Review”, Digestive Surgery 25:245-257 (2008). [cited by applicant]
Xu et al., “Excorporeal Normothermic Machine Perfusion Resuscitates Pig DCD Livers with Extended Warm Ischemia”, Journal of Surgical Research 173(2):e83-e88 (2012). [cited by applicant]
Zhao et al., “Cell-permeable Peptide Antioxidants Targeted to Inner Mitochondrial Membrane inhibit Mitochondrial Swelling, Oxidative Cell Death, and Reperfusion Injury”, The Journal of Biological Chemistry 279(33):34682… [cited by applicant]
Berendsen et al., “Hepatocyte viability and ATP content decrease linearly over time during conventional cold storage of rat liver grafts”, Transplantation Proceedings 43(5):1484-1488 (2011). [cited by applicant]
Bessems et al., “Improved Machine Perfusion Preservation of the Non-Heart-Beating Donor Rat Liver Using Polysol: A New Machine Perfusion Preservation Solution”, Liver Transplantation 11(11):1379-1388 (2005). [cited by applicant]
Bessems et al., “Machine Perfusion Preservation of the Pig Liver Using a New Preservation Solution, Polysol”, Transplantation Proceedings 38:1238-1242 (2006). [cited by applicant]
Brockmann et al., “Normothermic Perfusion: A New Paradigm for Organ Preservation”, Annals of Surgery 250(1):1-6 (2009). [cited by applicant]
Buis et al., “Altered bile composition after liver transplantation is associated with the development of nonanastomotic biliary strictures”, Journal of Hepatology 50:69-79 (2009). [cited by applicant]
Butler et al., “Successful Extracorporeal Porcine Liver Perfusion for 72 HR”, Transplantation 73(8):1212-1218 (2002). [cited by applicant]
Chen et al., “Effective Application of ET-Kyoto Solution for Clinical Lung Transplantation”, Transplantation Proceedings 36:2812-2815 (2004). [cited by applicant]
Cypel et al., “Normothermic Ex Vivo Perfusion Prevents Lung Injury Compared to Extended Cold Preservation for Transplantation”, American Journal of Transplantation 9:2262-2269 (2009). [cited by applicant]
De Rougemont et al., “One Hour Hypothermic Oxygenated Perfusion (HOPE) Protects Nonviable Liver Allografts Donated After Cardiac Death”, Annals of Surgery 250(5):674-683 (2009). [cited by applicant]
De Vera et al., “Liver Transplantation Using Donation After Cardiac Death Donors: Long-Term Follow-Up from a Single Center”, American Journal of Transplantation 9:773-781 (2009). [cited by applicant]
Donato et al., “Liver Grafts Preserved in Celsior Solution as Source of Hepatocytes for Drug Metabolism Studies: Comparison With Surgical Liver Biopsies”, Drug Metabolism and Disposition 33(1):108-114 (2005). [cited by applicant]
Fahy et al., “Cryopreservation of Complex Systems: The Missing Link in the Regenerative Medicine Supply Chain”, Rejuvenation Research 9(2):279-291 (2006). [cited by applicant]
Ferrigno et al., “Machine perfusion at 20° C. reduces preservation damage to livers from non-heart beating donors”, Cryobiology 62:152-158 (2011). [cited by applicant]
Friend et al., “Normothermic Perfusion of the Isolated Liver”, Transplantation Proceedings 33:3436-3438 (2001). [cited by applicant]
Geuken et al., “Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation”, Journal of Hepatology 41:1017-1025 (2004). [cited by applicant]
Giknis et al., “Clinical Laboratory Parameters for the Crl:CD(SD) Rat”, Charles River Laboratories 1-14 (2006). [cited by applicant]
Guarrera et al., “Hypothermic Machine Preservation in Human Liver Transplantation: The First Clinical Series”, American Journal of Transplantation 10:372-381 (2010). [cited by applicant]
Guibert et al., “Organ Preservation: Current Concepts and New Strategies for the Next Decade”, Transfusion Medicine and Hemotherapy 38:125-142 (2011). [cited by applicant]
Hertl et al., “Evidence of Preservation Injury to Bile Ducts by Bile Salts in the Pig and Its Prevention by Infusions of Hydrophilic Bile Salts”, Hepatology 21(4): 1130-1137 (1995). [cited by applicant]
Hoekstra et al., “Bile Salt Toxicity Aggravates Cold Ischemic Injury of Bile Ducts After Liver Transplantation in Mdr2 +/− Mice”, Hepatolgy 43(5):1022-1031 (2006). [cited by applicant]
Hughes et al., “Isolation of Hepatocytes from Livers from Non-Heart-Beating Donors for Cell Transplantation”, Liver Transplantation 12:713-717 (2006). [cited by applicant]
Imber et al., “Optimisation of Bile Production during Normothermic Preservation of Porcine Livers”, American Journal of Transplantation 2:593-599 (2002). [cited by applicant]
Izamis M., “Ex vivo perfusion optimization of donor liver grafts for transplantation and cell isolation”, Doctoral dissertation, Massachusetts Institute of Technology 193-222 (2010). [cited by applicant]
Jain et al., “Long-Term Survival After Liver Transplantation in 4,000 Consecutive Patients at a Single Center”, Annals of Surgery 232(4):490-500 (2000). [cited by applicant]
Kamiike et al., “Adenine Nucleotide Metabolism and Its Relation to Organ Viability in Human Liver Transplantation”, Transplantation 45(1):138-143 (1988). [cited by applicant]
Koetting et al., “Donation After Cardiac Death: Dynamic Graft Reconditioning During or After Ischemic Preservation?”, Artificial Organs 35(6):565-571 (2011). [cited by applicant]
Lanir et al., “Hepatic Transplantation Survival: Correlation with Adenine Nucleotide Level in Donor Liver”, Hepatology 8(3):471-475 (1988). [cited by applicant]
Lee et al., “Metabolic Flux Analysis of Postburn Hepatic Hypermetabolism”, Metabolic Engineering 2:312-327 (2000). [cited by applicant]
Luer et al., “Role of oxygen during hypothermic machine perfusion preservation of the liver”, Transplant International 23:944-950 (2010). [cited by applicant]
McCord, “Oxygen-Derived Free Radicals in Postischemic Tissue Injury”, The New England Journal of Medicine 312(3):159-163 (1985). [cited by applicant]
McCormack et al., “Use of Severely Steatotic Grafts in Liver Transplantation: A Matched Case-Control Study”, Annals of Surgery 246(6):940-948 (2007). [cited by applicant]
Minor et al., “Fibrinolysis in organ procurement for transplantation after cardiocirculatory compromise”, Thrombosis and Haemostasis 90:361-362 (2003). [cited by applicant]
Mitchell et al., “Energy Metabolism Following Prolonged Hepatic Cold Preservation: Benefits of Interrupted Hypoxia on the Adenine Nucleotide Pool in Rat Liver”, Cryobiology 39:130-137 (1999). [cited by applicant]
Miyagi et al., “The Significance of Preserving the Energy Status and Microcirculation in Liver Grafts From Non-Heart-Beating Donor”, Cell Transplantation 17:173-178 (2008). [cited by applicant]
Moore et al., “Impact of Donor, Technical, and Recipient Risk Factors on Survival and Quality of Life After Liver Transplantation”, Archives of Surgery 140(3):273-277 (2005). [cited by applicant]
Nelson et al., “An improved ex vivo method of primary porcine hepatocyte isolation for use in bioartificial liver systems”, European Journal of Gastroenterology & Hepatology 12(8):923-930 (2000). http://cat.inist.fr/?aM… [cited by applicant]
Okamoto et al., “Successful Sub-zero Non-freezing Preservation of Rat Lungs at -2° C. Utilizing a New Supercooling Technology”, Journal of Heart and Lung Transplantation 27(10):1150-1157 (2008). [cited by applicant]
Perk et al., “A Metabolic Index of Ischemic Injury for Perfusion-Recovery of Cadaveric Rat Livers”, PLoS ONE 6(12):e28518 (2011). (11 pages). [cited by applicant]
Peter et al., “Hepatic Control of Perfusate Homeostasis During Normothermic Extrocorporeal Preservation”, Transplantation Proceedings 35:1587-1590 (2003). [cited by applicant]
Reddy et al., “Non-Heart-Beating Donor Porcine Livers: the Adverse Effect of Cooling”, Liver Transplantation 11(1):35-38 (2005). [cited by applicant]
Reddy et al., “Preservation of Porcine Non-Heart-Beating Donor Livers By Sequential Cold Storage and Warm Perfusion”, Transplantation 77(9):1328-1332 (2004). [cited by applicant]
Sakaguchi et al., “Preservation of Myocardial Function and Metabolism at Subzero Nonfreezing Temperature Storage of the Heart”, The Journal of Heart and Lung Transplantation 15(11):1101-1107 (1996). [cited by applicant]
Serracino-Inglott et al., “Hepatic ischemia-reperfusion injury”, The American Journal of Surgery 181:160-166 (2001). [cited by applicant]
Soltys et al., “Successful Nonfreezing, Subzero Preservation of Rat Liver with 2,3-Butanediol and Type I Antifreeze Protein”, Journal of Surgical Research 96(1):30-34 (2001). [cited by applicant]
St Peter et al., “Extended preservation of non-heart-beating donor livers with normothermic machine perfusion”, British Journal of Surgery 89:609-616 (2002). [cited by applicant]
Sugimachi et al., “Nonmetabolizable glucose compounds impart cryotolerance to primary rat hepatocytes”, Tissue Eng 12(3):579-588 (2006). [cited by applicant]
Taylor et al., “Twenty-Four Hour Hypothermic Machine Perfusion Preservation of Porcine Pancreas Facilitates Processing for Islet Isolation”, Transplantation Proceedings 40:480-482 (2008). [cited by applicant]
Tolboom et al., “A Model for Normothermic Preservation of the Rat Liver”, Tissue Engineering 13(8):2143-2151 (2007). [cited by applicant]
Tolboom et al., “Recovery of Warm Ischemic Rat Liver Grafts by Normothermic Extracorporeal Perfusion”, Transplantation 87(2):170-177 (2009). [cited by applicant]
Tolboom et al., “Sequential Cold Storage and Normothermic Perfusion of the Ischemic Rat Liver”, Tranplantation Proceedings 40(5):1306-1309 (2008). [cited by applicant]
Afonso et al., “Critical parameters in blood processing fort-cell assays: validation on elispot and tetramer platforms,” J Immunol Methods, 2010, 359(1-2):28-36. [cited by applicant]
Almanza et al., “Endoplasmic reticulum stress signalling—from basic mechanisms to clinical applications,” FEBS J., 2019, 286(2):241-278. [cited by applicant]
Amir et al., “Improved viability and reduced apoptosis in sub-zero 21-hour preservation of transplanted rat hearts using anti-freeze proteins,” J. Heart Lung Transplant., 2005, 24(11):1915-1929. [cited by applicant]
Amir et al., “Prolonged 24-hour subzero preservation of heterotopically transplanted rat hearts using antifreeze proteins derived from arctic fish,” Ann. Thorac. Surg., May 2004, 77(5):1648-1655. [cited by applicant]
Amir et al., “Subzero nonfreezing cryopresevation of rat hearts using antifreeze protein I and antifreeze protein III,” Cryobiology, Jun. 2004, 48(3):273-282. [cited by applicant]
Ardehali et al., “Ex-vivo perfusion of donor hearts for human heart transplantation (Proceed II): a prospective, open-label, multicentre, randomised non-inferiority trial,” The Lancet, Jun. 2015, 385(9987):2577-2584, 8 … [cited by applicant]
Armstrong et al., “The hydrodynamic radii of macromolecules and their effect on red blood cell aggregation,” Biophys. J, Dec. 2004, 87(6):4259-70. [cited by applicant]
Arrington and McNamara, “Effect of agitation on platelet aggregation and microaggregate formation in banked blood,” Ann. Surg., 1975, 181 (2):243-44. [cited by applicant]
AU Office Action in Australian Appln. No. 2015301303 dated Sep. 28, 2020, 4 pages. [cited by applicant]
Avruch et al., “A novel model for ex situ reperfusion of the human liver following subnormothermic machine perfusion,” Technology (Singap World Sci.), Dec. 2017, 5(4):196-200, 5 pages. [cited by applicant]
Bang et al., “Antifreeze peptides and glycopeptides, and their derivatives: Potential uses in biotechnology,” Marine Drugs, Jun. 2013, 11(6):2013-2041. [cited by applicant]
Baskin-Bey et al., “Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in steatotic livers after cold ischemia-warm reperfusion injury,” Am. J. Physiol. Gastrointest. Liver Physiol., Feb. 2005, 28… [cited by applicant]
Baskin-Bey et al., “Clinical Trial of the Pan-Caspase Inhibitor, IDN- 6556, in Human Liver Preservation Injury,” Am J Transplant, 2007, 7(1):218-25. [cited by applicant]
BDJ.co.jp [online], “BD Vacuteina Blood Collecting Tube,” 2022, retrieved on Aug. 16, 2022, retrieved from URL<https://www.bdj.co.jp/pas/products/mekkin/1f3pro00000ntpw3.html>, 2 pages (with English translation). [cited by applicant]
Behrends et al., “Network organization of the human autophagy system,” Nature, Jul. 2010, 466(7302):68-76. [cited by applicant]
Berendsen et al., “Supercooling Enables Long-Term Transplantation Survival Following 4 Days of Liver Preservation,” Nat. Med. Jul. 2014, 20(7):790-793, 5 pages. [cited by applicant]
Bergan et al., “Low molecular weight dextran in treatment of severe ischemia,” Arch. Surg., 1965, 91(2):338. [cited by applicant]
Best, “Cryoprotectant Toxicity: Facts, Issues, and Questions,” Rejuvenation Res., Oct. 2015, 18(5):422-436. [cited by applicant]
Boteon et al., “Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion,” World J. Gastroenterol., Dec. 2017, 23(48):8443-8451. [cited by applicant]
Brenner et al., “Decoding cell death signals in liver inflammation,” J Hepatol, Sep. 2013, 59(3):583-94. [cited by applicant]
Briard et al., “Small molecule ice recrystallization inhibitors mitigate red blood cell lysis during freezing, transient warming and thawing,” Sci. Rep., 2016, 29(6):23619, 10 pages. [cited by applicant]
Brill et al., “Neutrophil extracellular traps promote deep vein thrombosis in mice,” J Thromb. Haemost., 2012, 10(1):136-44. [cited by applicant]
Brinkmann and Zychlinsky, “Neutrophil extracellular traps: is immunity the second function of chromatin?,” J Cell Biol., 2012, 198(5):773-83. [cited by applicant]
Brown et al., “Morphological, biochemical, and functional changes in human platelets subjected to shear stress,” J Lab. Clin. Med., 1975, 86(3):462-71. [cited by applicant]
Bruinsma and Uygun, “Subzero organ preservation: the dawn of a new ice age?,” Curr. Opin. Organ Transplant., 2017, 22(3):281-286, 6 pages. [cited by applicant]
Bruinsma et al., “Determination and Extension of the Limits to Static Cold Storage with Subnormothermic Machine Perfusion,” The International Journal of Artificial Organs, 2013, 36(11):775-780. [cited by applicant]
Bruinsma et al., “Metabolic profiling during ex vivo machine perfusion of the human liver,” Sci. Rep., 2016, 6:22415, 13 pages. [cited by applicant]
Bruinsma et al., “Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation: Subnormothermic Machine Perfusion of Human Livers,” Am. J. Transplant., 2014, 14(6):1400-… [cited by applicant]
Bruinsma et al., “Supercooling preservation and transplantation of the rat liver,” Nat. Protoc., Mar. 2015, 10(3):484-494. [cited by applicant]
Burkey et al., “Understanding Poly(vinyl alcohol)-Mediated Ice Recrystallization Inhibition through Ice Adsorption Measurement and pH Effects,” Biomacromolecules, 2018, 19(1):248-55, 40 pages. [cited by applicant]
CA Office Action in Canadian Appln. No. 2,957,535, dated Aug. 20, 2021, 5 pages. [cited by applicant]
Campbell et al., “Restoration of ovarian function and natural fertility following the cryopreservation and autotransplantation of whole adult sheep ovaries,” Hum. Reprod., Jun. 2014, 29(8):1749-1763. [cited by applicant]
Celik et al., “Microfluidic experiments reveal that antifreeze proteins bound to ice crystals suffice to prevent their growth,” Proc. Nat'l Acad. Sci. U S A, 2013, 110(4):1309-1314. [cited by applicant]
Chawade et al., “Normalyzer: a tool for rapid evaluation of normalization methods for omics data sets,” J. Proteome Res., 2014, 13(6):3114-3120. [cited by applicant]
Chen et al., “A Versatile Polypharmacology Platform Promotes Cytoprotection and Viability of Human Pluripotent and Differentiated Cells,” Nature Methods, 2021, 18:528-541. [cited by applicant]
Cheng et al., “A microfluidic device for practical label-free CD4(+) t cell counting of HIV-infected subjects,” Lab Chip, Feb. 2007, 7(2): 170-78. [cited by applicant]
Chien et al., “Blood viscosity: influence of erythrocyte aggregation,” Science, Aug. 1967, 157 (3790): 829-31. [cited by applicant]
Chinese Office Action in Application No. 201580054390.3, dated Mar. 19, 2018, 8 pages (with English translation). [cited by applicant]
Cho et al., “Changes in the expression of cell cycle regulators during rat liver regeneration after partial hepatectomy,” Exp. Mol. Med., 1996, 28(4):187-191. [cited by applicant]
CN Office Action in Chinese Appln. No. 201580054390.3, dated Nov. 15, 2021, 17 pages (with English summary). [cited by applicant]
CN Office Action in Chinese Appln. No. 201580054390.3, dated Feb. 3, 2020, 19 pages (with English translation). [cited by applicant]
CN Office Action in Chinese Appln. No. 201580054390.3, dated Jun. 28, 2020, 12 pages (with English translation). [cited by applicant]
Costanzo et al., “Hibernation physiology, freezing adaptation and extreme freeze tolerance in a northern population of the wood frog,” J. Exp. Biol., Sep. 2013, 216(Pt 18):3461-3473. [cited by applicant]
De Rose et al., “Granulocyte contamination dramatically inhibits spot formation in aids virus-specific elispot assays: analysis and strategies to ameliorate,” J Immunol Methods, 2005, 297(1-2): 177-86. [cited by applicant]
De Vries et al., “Abstract 615.2: Extending the Human Liver Preservation Time for Transplantation by Supercooling,” Transplantation, Jul. 2018, 102(7S):S396. [cited by applicant]
De Vries et al., “Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution,” Am. J. Transplant. Of… [cited by applicant]
De Vries et al., “Supercooling extends preservation time of human livers,” Nat. Biotechnol., Oct. 2019, 37(10):1131-1136, 10 pages. [cited by applicant]
De Vries et al., “Systems engineering the organ preservation process for transplantation,” Curr. Op. Biotechnol., Aug. 2019, 58:192-201. [cited by applicant]
Devireddy et al., “Liver Freezing Response of the Freeze-Tolerant Wood Frog, Rana sylvatica, in the Presence and Absence of Glucose. I. Experimental Measurements,” Cryobiology, 1999, 38:310-326. [cited by applicant]
Do Amaral et al., “Hepatocyte responses to in vitro freezing and β-adrenergic stimulation: Insights into the extreme freeze tolerance of subarctic Rana sylvatica,” J. Exp. Zool. Part Ecol. Genet. Physiol., 2015, 323(2):… [cited by applicant]
Dobin et al., “STAR: ultrafast universal RNA-seq aligner,” Bioinformatics, Jan. 2013, 29(1):15-21. [cited by applicant]
Eickhoff et al., “Contrasting Behavior of Antifreeze Proteins: Ice Growth Inhibitors and Ice Nucleation Promoters,” J. Phys. Chem. Lett., 2019,10(5):966-972. [cited by applicant]
Emadali et al., “Distinct endoplasmic reticulum stress responses are triggered during human liver transplantation,” J. Pathol., Sep. 2005, 207(1):111-118. [cited by applicant]
EP Extended European Search Report in European Appln. No. 20150503.9, dated Jun. 15, 2020, 10 pages. [cited by applicant]
Eshmuminov et al., “An integrated perfusion machine preserves injured human livers for 1 week,” Nat. Biotechnol., Feb. 2020, 38(2):189-198. [cited by applicant]
Extended European Search Report in Application No. 15829066.8, dated Mar. 5, 2018, 10 pages. [cited by applicant]
Fahy et al., “Cryopreservation of organs by vitrification: perspectives and recent advances,” Cryobiology, Apr. 2004, 48(2):157-178. [cited by applicant]
Fahy et al., “Physical and biological aspects of renal vitrification,” Organogenesis, 2009, 5(3):167-175. [cited by applicant]
Fahy, “Analysis of “solution effects” injury: Cooling rate dependence of the functional and morphological sequellae of freezing in rabbit renal cortex protected with dimethyl sulfoxide,” Cryobiology, 1981, 18(6):550-570. [cited by applicant]
Fairlie et al., “Crosstalk between apoptosis and autophagy signaling pathways,” Int Rev Cell Mol Biol, 2020, 352:115-158. [cited by applicant]
Farrant, “Mechanism of cell damage during freezing and thawing and its prevention,” Nature, 1965, 205:1284-1287. [cited by applicant]
Fuchs et al., “Neutrophils release extracellular DNA traps during storage of red blood cell units,” Transfusion, 2013, 53(12):3210-16. [cited by applicant]
Fuchs et al., “Novel cell death program leads to neutrophil extracellular traps,” J Cell Biol., Jan. 2007, 176(2):231-41. [cited by applicant]
Galluzzi et al., “Caspases Connect Cell-Death Signaling to Organismal Homeostasis,” Immunity, 2016, 44:221-31. [cited by applicant]
Garcia-Romo et al., “Netting neutrophils are major inducers of type i ifn production in pediatric systemic lupus erythematosus,” Sci. Transl. Med., Mar. 2011, 3(73):73ra20. [cited by applicant]
GE Healthcare, Data File 18-1158-27 AB, Cell preparation, 2007, 6 pages. [cited by applicant]
Gearing et al., “CiiiDER: a tool for predicting and analysing transcription factor binding sites,” PLoS One, 2019, 14:e0215495, 12 pages. [cited by applicant]
Gervin et al., “The effect of agitation of stored human blood on microaggregate formation,” Transfusion, Jan. 1978, 18(1):73-78. [cited by applicant]
Giwa et al., “The promise of organ and tissue preservation to transform medicine,” Nat Biotechnol., 2017, 35(6):530-542. [cited by applicant]
Graw et al., “proteiNorm—A User-Friendly Tool for Normalization and Analysis of TMT and Label-Free Protein Quantification,” ACS Omega 2020, 5(40):25625-25633. [cited by applicant]
Grimberg et al., “p53-Dependent and p53-Independent Induction of Insulin-Like Growth Factor Binding Protein-3 by Deoxyribonucleic Acid Damage and Hypoxia,” J. of Clin. Endocrinology & Metabolism, Jun. 2005, 90(6):3568-7… [cited by applicant]
Gringeri et al., “Subnormothermic machine perfusion for non-heart-beating donor liver grafts preservation in a Swine model: a new strategy to increase the donor pool?,” Transplant. Proc., 2012, 44(7):2026-2028. [cited by applicant]
Gu et al., “circlize Implements and enhances circular visualization in R,” Bioinformatics, Oct. 2014, 30(19):2811-2, 2 pages. [cited by applicant]
Guicciardi and Gores, “Apoptosis: a mechanism of acute and chronic liver injury,” Gut, 2005, 54:1024-33. [cited by applicant]
Guicciardi et al., “Apoptosis and necrosis in the liver,” Compr Physiol, 2013, 3(2):977-1010. [cited by applicant]
Hamilton et al., “Successful preservation of canine small intestine by freezing,” J. Surg. Res., 1973, 14(4):313-318. [cited by applicant]
Hardwick, “Blood processing,” ISBT Sci. Ser., 2008, 3:148-76. [cited by applicant]
Harrison et al., “A randomized, placebo-controlled trial of emricasan in patients with NASH and F1-F3 fibrosis,” J Hepatol, 2020, 72:816-827. [cited by applicant]
Hasan et al., “Ice Recrystallization Inhibiting Polymers Enable Glycerol-Free Cryopreservation of Microorganisms,” Biomacromolecules, 2018, 19(8):3371-3376. [cited by applicant]
Hoglen et al., “A caspase inhibitor, IDN-6556, ameliorates early hepatic injury in an ex vivo rat model of warm and cold ischemia,” Liver Transpl, 2007, 13:361-6. [cited by applicant]
Hoglen et al., “Characterization of IDN-6556 (3-{2-(2-tert-Butylphenylaminooxaly1)-amino]-propionylamino }-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid): a Liver-Targeted Caspase Inhibitor,” The Journal of Pharm… [cited by applicant]
Huang et al., “A microfluidics approach for the isolation of nucleated red blood cells (NRBCs) from the peripheral blood of pregnant women,” Prenat Diagn, Oct. 2008, 28(10):892-99. [cited by applicant]
Huber et al., “Variance stabilization applied to microarray data calibration and to the quantification of differential expression,” Bioinformatics, 2002, 18(Suppl 1):S96-104. [cited by applicant]
Huestis and Glasser, “The neutrophil in transfusion medicine,” Transfusion., Jul. 1994, 34(7):630-46. [cited by applicant]
Hunt et al., “Freeze-substitution and isothermal freeze-fixation studies to elucidate the pattern of ice formation in smooth muscle at 252 K (-21° C.),” J. Microsc., 1982, 125(2):177-186. [cited by applicant]
Hunt, “Studies on cellular structure and ice location in frozen organs and tissues: The use of freeze-substitution and related techniques,” Cryobiology, 1984, 21(4):385-402. [cited by applicant]
IN Office Action in Indian Appln. No. 201717004487, dated Sep. 25, 2020, 7 pages. [cited by applicant]
International Preliminary Report on Patentability in International Application No. PCT/US2015/043269, dated Feb. 7, 2017. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2020/017310, mailed on Jul. 21, 2020, 24 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2022/072229, mailed on Oct. 6, 2022, 15 pages. [cited by applicant]
International Search Report and Written Opinion mailed Oct. 26, 2015 in International Application No. PCT/US15/43269, 22 pages. [cited by applicant]
Invitation to Pay Additional Fees And, Where Applicable, Protest Fee in International Appln. No. PCT/US2020/017310, mailed on Apr. 30, 2020, 3 pages. [cited by applicant]
Invitation to Pay Additional Fees And, Where Applicable, Protest Fee in International Appln. No. PCT/US2022/072229, mailed on Jul. 18, 2022, 3 pages. [cited by applicant]
Ishiguro and Rubinsky, “Mechanical interactions between ice crystals and red blood cells during directional solidification,” Cryobiology, 1994, 31(5):483-500. [cited by applicant]
Ishine et al., “A Histological Analysis of Liver Injury in Freezing Storage,” Cryobiology, 1999, 39(3):271-277. [cited by applicant]
Ishine et al., “Transplantation of Mammalian Livers Following Freezing: Vascular Damage and Functional Recovery,” Cryobiology, 2000, 40(1):84-89. [cited by applicant]
Jan et al., “The disaggregation effect of dextran 40 on red cell aggregation in macromolecular suspensions,” Biorheology, 1982, 19(4):543-54. [cited by applicant]
Jassem et al., “Normothermic machine perfusion (NMP) inhibits proinflammatory responses in the liver and promotes regeneration,” Hepatology, 2019, 70(2):682-695, 34 pages. [cited by applicant]
JP Office Action in Japanese Appln. No. 2017-50678, dated May 28, 2019, 7 pages (with English translation). [cited by applicant]
JP Office Action in Japanese Appln. No. 2020-066388, dated Mar. 23, 2021, 10 pages (with English translation). [cited by applicant]
Karabacak et al., “Microfluidic, marker-free isolation of circulating tumor cells from blood samples,” Nat Protoc, Mar. 2014, 9(3):694-710. [cited by applicant]
Karimian et al., “Ex Situ normothermic machine perfusion of donor livers,” J. Vis. Exp., 2015, 99:e52688, 9 pages. [cited by applicant]
Katenz et al., “Cryopreservation of primary human hepatocytes: The benefit of trehalose as an additional cryoprotective agent,” Liver Transplant., 2007, 13(1):38-45. [cited by applicant]
Klopfleisch et al., “Excavation of a buried treasure—DNA, mRNA, miRNA and protein analysis in formalin fixed, paraffin embedded tissues,” Histol Histopathol, 2011, 26(6):797-810. [cited by applicant]
Kotz et al., “Clinical microfluidics for neutrophil genomics and proteomics,” Nat. Med., Sep. 2010, 16(9): 1042-47. [cited by applicant]
Kramer et al., “Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18,” Cancer Res, 2004, 64(5):1751-6. [cited by applicant]
Kuhne et al., “Flow Cytometric Evaluation of Platelet Activation in Blood Collected Into EDTA vs. Diatube-H, a Sodium Citrate Solution Supplemented With Theophylline, Adenosine, and Dipyridamole,” Am J Hematol, Sep. 199… [cited by applicant]
Kuiper et al., “The biological function of an insect antifreeze protein simulated by molecular dynamics,” eLife, 2015, 4:e05142, 14 pages. [cited by applicant]
Laing et al., “Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, nonrandomised, prospective, single-arm trial,” BMJ Open, 2017, 7(1… [cited by applicant]
Lamming et al., “Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2),” FASEB J., 2014, 28(1):300-15, 16 pages. [cited by applicant]
Layne et al., “Freeze duration influences postfreeze survival in the frog Rana sylvatica,” J. Exp. Zool., 1998, 280(2):197-201. [cited by applicant]
Libbrecht, “Physical Dynamics of Ice Crystal Growth,” Annu. Rev. Mater. Res., 2017, 47(1):7.1-7.25. [cited by applicant]
Lin and Carroll, “The effect of calcium and magnesium on frozen rat uteri, and the calcium content of uteri frozen by various procedures,” Cryobiology, 1968, 5(2):105-108. [cited by applicant]
Liu and Green, “Endoplasmic reticulum stress and liver diseases,” Liver Res., 2019, 3(1):55-64. [cited by applicant]
Livak and Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method,” Methods, Dec. 2001, 25(4):402-8. [cited by applicant]
Lowe, “Blood rheology in vitro and in vivo,” Baillieres. Clin. Haematol., 1987, 1(3):597-636. [cited by applicant]
Luu and Storey, “Solving Donor Organ Shortage with Insights from Freeze Tolerance in Nature: Activating endogenous antioxidant systems with non-coding RNA to precondition donor organs,” BioEssays News Rev. Mol. Cell. De… [cited by applicant]
Maheswaran et al., “Detection of mutations in egfr in circulating lung-cancer cells,” N. Engl. J. Med., Jul. 2008, 359( 4):366-77. [cited by applicant]
Martins et al., “The role of normothermic machine perfusion in liver transplantation,” Int J Surg, 2020, 82(S):52-60, 9 pages. [cited by applicant]
Med.Kyushu-u.ac.jp [online], “Kyushu University Hospital Laboratory Inspection Section Newsletter,” Apr. 20, 2007, retrieved on Aug. 16, 2022, retrieved from URL<https://www.med.kyushu-u.ac.jp/cclm/html/tayori/kensa32.h… [cited by applicant]
Mergental et al., “Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation,” Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg., 2016, 16(11):3235-3245. [cited by applicant]
Mergental et al., “Transplantation of discarded livers following viability testing with normothermic machine perfusion,” Nat. Commun., 2020, 11:2939, 13 pages. [cited by applicant]
Michalopoulos and Bhushan, “Liver regeneration: biological and pathological mechanisms and implications,” Nat. Rev. Gastroenterol. Hepatol., 2021, 18:40-55, 16 pages. [cited by applicant]
Miyamoto and Sasakawa, “Studies on granulocyte preservation. III. Effect of agitation on granulocyte concentrates,” Transfusion, 1987, 27(2): 165-66. [cited by applicant]
Moss et al., “Observations on the effects of glycerol on the cold storage of the canine liver,” J. Surg. Res., 1966, 6(4):147-151. [cited by applicant]
Mueller et al., “Caspase 3 inhibition improves survival and reduces early graft injury after ischemia and reperfusion in rat liver transplantation,” Transplantation, 2004, 78(9):1267-73. [cited by applicant]
Mugnano et al., “Antifreeze glycoproteins promote intracellular freezing of rat cardiomyocytes at high subzero temperatures,” Am. J. Physiol. Regul. Integr. Comp. Physiol., 1995, 269(2):R474-479. [cited by applicant]
Murata and Tanaka, “Liquid-liquid transition without macroscopic phase separation in a water-glycerol mixture,” Nat. Mater., 2012, 11:436-443. [cited by applicant]
Nagrath et al., “Isolation of rare circulating tumour cells in cancer patients by microchip technology,” Nature, Dec. 2007, 450(7173): 1235-39. [cited by applicant]
Nasralla et al., “A randomized trial of normothermic preservation in liver transplantation,” Nature, 2018, 557(7703):50-56, 23 pages. [cited by applicant]
Nassar et al., “Ex Vivo Normothermic Machine Perfusion Is Safe, Simple, and Reliable: Results From a Large Animal Model,” Surg. Innov., 2015, 22:61-69, 10 pages. [cited by applicant]
Natori et al., “Apoptosis of sinusoidal endothelial cells occurs during liver preservation injury by a caspase-dependent mechanism,” Transplantation, 1999, 68:89-96. [cited by applicant]
Natori et al., “The caspase inhibitor IDN-6556 prevents caspase activation and apoptosis in sinusoidal endothelial cells during liver preservation injury,” Liver Transpl, 2003, 9(3):278-84. [cited by applicant]
Naullage et al., “Molecular Recognition of Ice by Fully Flexible Molecules,” J. Phys. Chem. C, 2017, 121(48):26949-26957. [cited by applicant]
Neu and Meiselman, “Depletion-mediated red blood cell aggregation in polymer solutions,” Biophys. J, Nov. 2002, 83(5):2482-90. [cited by applicant]
Neu et al., “Aggregation of human RBC in binary dextran-peg polymer mixtures,” Biorheology., 2001, 38(1):53-68. [cited by applicant]
Nicholson et al., “Comparison of T and B cell analyses on fresh and aged blood,” J Immunol Methods, Oct. 1984, 73(1):29-40. [cited by applicant]
Nösser et al., “Development of a Rat Liver Machine Perfusion System for Normothermic and Subnormothermic Conditions,” Tissue Eng. Part A, 2020, 26(1):57-65. [cited by applicant]
Notice of Allowance in Chinese Appln. No. 201580054390.3, dated Mar. 9, 2022, 3 pages (with English translation). [cited by applicant]
O'Connor et al., “Usefulness of Soluble and Surface-Bound P-Selectin in Detecting Heightened Platelet Activity in Patients With Congestive Heart Failure,” Am J Cardiol., May 1999, 83(9), 1345-1349. [cited by applicant]
Office Action in Canadian Appln. No. 2,957,535, dated Mar. 10, 2022, 4 pages. [cited by applicant]
Office Action in Chinese Application No. 201580054390.3, dated Dec. 10, 2018, 12 pages (with English translation). [cited by applicant]
Office Action in Chinese Application No. 201580054390.3, dated Apr. 23, 2019, 25 pages (with English translation). [cited by applicant]
Office Action in Japanese Appln. No. 2020-066388, dated Aug. 2, 2022, 6 pages (with English translation). [cited by applicant]
Office Action in Japanese Appln. No. 2020-066388, dated Nov. 22, 2021, 9 pages (with English translation). [cited by applicant]
Ohman et al., “Activation of autophagy during normothermic machine perfusion of discarded livers is associated with improved hepatocellular function,” Am J Physiol Gastrointest Liver Physiol., Jan. 2022, 322(1):G21-G33. [cited by applicant]
Op den Dries et al., “Hypothermic Oxygenated Machine Perfusion Prevents Arteriolonecrosis of the Peribiliary Plexus in Pig Livers Donated after Circulatory Death,” PLoS ONE, 2014, 9;e88521, 10 pages. [cited by applicant]
Orning and Lien, “Multiple roles of caspase-8 in cell death, inflammation, and innate immunity,” J Leukoc Biol, 2020, 109:121-141. [cited by applicant]
Orringer et al., “Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: a randomized controlled trial,” JAMA., Nov. 2001, 286(17):2099-2106. [cited by applicant]
Ott et al., “Solid-liquid phase equilibria in water + ethylene glycol,” J. Chem. Thermodyn., 1972, 4:123-126. [cited by applicant]
Owen et al., “Loss of T cell responses following long-term cryopreservation,” Journal of Immunological Methods, Sep. 2007, 326(1-2):93-115. [cited by applicant]
Ozkumur et al., “Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells,” Sci. Transl. Med., 2013, 5(179): 179ra47. [cited by applicant]
Pegg, “The relevance of ice crystal formation for the cryopreservation of tissues and organs,” Cryobiology, 2010, 60(3 supp):S36-44. [cited by applicant]
Perk et al., “A fitness index for transplantation of machine-perfused cadaveric rat livers,” BMC Research Notes, 2012, 5:325, 7 pages. [cited by applicant]
Posevitz-Fejfár et al., “Effects of blood transportation on human peripheral mononuclear cell yield, phenotype and function: implications for immune cell biobanking,” PLoS ONE, Dec. 2014, 9(12):e115920, 19 pages. [cited by applicant]
QiagenBioinformatics.com [online], “Ingenuity Pathway Analysis,” available on or before Feb. 21, 2019, via Internet Archive: Wayback MachineURL<http://web.archive.org/web/20190221071551/https://www.qiagenbioinformatics.… [cited by applicant]
Raigani et al., “Pumping new life into old ideas: Preservation and rehabilitation of the liver using ex situ machine perfusion,” Artif Organs, 2020, 44(2):123-128, 6 pages. [cited by applicant]
Raigani et al., “Viability testing of discarded livers with normothermic machine perfusion: Alleviating the organ shortage outweighs the cost,” Clin. Transplant., 2020, 34(11):e14069, 26 pages. [cited by applicant]
Ramanujam et al., “Stabilization of Nucleic Acids in Whole Blood: An Alternative to Guthrie Cards,” Biotechniques, Nov. 1993, 15: 825-8. [cited by applicant]
Ray, “Preserving the liver for transplantation,” Nat. Rev. Gastroenterol. Hepatol., 2018, 15(6):327. [cited by applicant]
Reimers et al., “Potentiation by red blood cells of shear-induced platelet aggregation: relative importance of chemical and physical mechanisms,” Blood, Dec. 1984, 64(6):1200-1206. [cited by applicant]
Ritchie et al., “limma powers differential expression analyses for RNA-sequencing and microarray studies,” Nucleic Acids Res., 2015, 43(7):e47, 13 pages. [cited by applicant]
Robinson and Newsholme, “Some properties of hepatic glycerol kinase and their relation to the control of glycerol utilization,” Biochem. J., 1969, 112(4):455-464. [cited by applicant]
Robinson et al., “edgeR: a Bioconductor package for differential expression analysis of digital gene expression data,” Bioinformatics, 2010, 26(1):139-140. [cited by applicant]
Roman et al., “T-Cell Activation under Hypoxic Conditions Enhances IFN-γ Secretion,” Am. J. Respir. Cell Mol. Biol., Jan. 2010, 42(1):123-8. [cited by applicant]
Rubinsky et al., “The process of freezing and the mechanism of damage during hepatic cryosurgery,” Cryobiology, 1990, 27(1):85-97. [cited by applicant]
Sanders et al., “The effect of rapamycin on DNA synthesis in multiple tissues from late gestation fetal and postnatal rats,” Am. J. Physiol. Cell Physiol., 2008, 295:C406-C413. [cited by applicant]
Schlegel and Dutkowski, “Letter to editor: repair or prevent: what is the real impact of normothermic machine perfusion in liver transplantation?,” Hepatology, 2019, 70(6):2231-2232, 4 pages. [cited by applicant]
Schmid-Schonbein et al., “On the shear rate dependence of red cell aggregation in vitro,” J Clin. Invest., 1968, 47(6): 1447-54. [cited by applicant]
Searle et al., “Chromatogram libraries improve peptide detection and quantification by data independent acquisition mass spectrometry,” Nat. Commun., 2018, 9:5128, 12 pages. [cited by applicant]
Shannon et al., “Cytoscape: a software environment for integrated models of biomolecular interaction networks,” Genome Res., 2003, 13(11):2498-504. [cited by applicant]
Shen et al., “Decreased hepatocyte autophagy leads to synergistic IL-1β and TNF mouse liver injury and inflammation,” Hepatology, 2020, 72:595-608, 31 pages. [cited by applicant]
Sosa et al., “Early cytokine signatures of ischemia/reperfusion injury in human orthotopic liver transplantation,” JCI Insight, 2016, 1:e89679, 17 pages. [cited by applicant]
Spindler et al., “Dimethyl sulfoxide and ethylene glycol promote membrane phase change during cryopreservation,” Cryo Lett., 2011, 32(2):148-157. [cited by applicant]
Sridharan et al., “Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics,” Metabolites, 2017, 7(4):e58, 18 pages. [cited by applicant]
SRTR.org [online], “Organ Procurement Organization (OPO) Reports,” Jan. 2020, retrieved on Aug. 9, 2022, retrieved from URL<https://www.srtr.org/reports/opo-specific-reports/>, 6 pages. [cited by applicant]
Stephens et al., “The dielectrophoresis enrichment of CD34+ cells from peripheral blood stem cell harvests,” Bone Marrow Transplant, Oct. 1996, 18:777-82. [cited by applicant]
Storey et al., “Cryomicroscopic analysis of freezing in liver of the freeze-tolerant wood frog,” Am. J. Physiol. Regul. Integr. Comp. Physiol., 1992, 263:R185-R194. [cited by applicant]
Storey, “Living in the Cold: Freeze-Induced Gene Responses in Freeze-Tolerant Vertebrates,” Clin. Exp. Pharmacol. Physiol., 1999, 26:57-63. [cited by applicant]
Taylor and Pegg “The effect of ice formation on the function of smooth muscle tissue stored at −21 or −60° C.,” Cryobiology, 1983, 20(1):36-40. [cited by applicant]
Taylor et al., “New Approaches to Cryopreservation of Cells, Tissues, and Organs,” Transfus. Med. Hemotherapy, 2019, 46(3):197-215. [cited by applicant]
Tessier et al., “Effect of Ice Nucleation and Cryoprotectants during High Subzero-Preservation in Endothelialized Microchannels,” ACS Biomater. Sci. Eng., 2018, 4(8):3006-3015, 25 pages. [cited by applicant]
Thomas et al., “Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice,” Blood, Jun. 2012, 119(26):6335-43. [cited by applicant]
Toner and Irimia, “Blood-on-a-chip,” Annu. Rev. Biomed. Eng., 2005, 7:77-103. [cited by applicant]
Toth et al., “Inhibition of polymer-induced red blood cell aggregation by poloxamer 188,” Biorheology, 2000, 37(4):301-12. [cited by applicant]
Urbańczyk et al., “Antifreeze glycopeptides: from structure and activity studies to current approaches in chemical synthesis,” Amino Acids, 2017, 49(2):209-222. [cited by applicant]
Uygun et al., “Diluted blood reperfusion as a model for transplantation of ischemic rat livers: alanine aminotransferase is a direct indicator of viability,” Transplant. Proc., 2010, 42(7):2463-2467. [cited by applicant]
Van den Ende, “Multifunctional fructans and raffinose family oligosaccharides,” Front. Plant Sci., 2013, 4:247, 11 pages. [cited by applicant]
Van Leeuwen et al., “Transplantation of high-risk donor livers after ex situ resuscitation and assessment using combined hypo- and normothermic machine perfusion: a prospective clinical trial,” Ann. Surg., 2019, 270(5):… [cited by applicant]
Van Rijn et al., “DHOPE-DCD Trial Investigators. Hypothermic machine perfusion in liver transplantation—a randomized trial,” N. Engl. J. Med., 2021, 384(15):1391-1401, 12 pages. [cited by applicant]
Vodkin and Kuo, “Extended criteria donors in liver transplantation,” Clin. Liver. Dis., 2017, 21(2):289-301, 13 pages. [cited by applicant]
Warnecke et al., “Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study,” Lancet Respir.… [cited by applicant]
Watson and Jochmans, “From “Gut Feeling” to Objectivity: Machine Preservation of the Liver as a Tool to Assess Organ Viability,” Curr. Transplant Reports, 2018, 5(1):72-81. [cited by applicant]
Watson et al., “Observations on the ex situ perfusion of livers for transplantation,” Am. J. Transplant., 2018, 18(8):2005-2020. [cited by applicant]
Weng et al., “Molecular Dynamics at the Interface between Ice and Poly(vinyl alcohol) and Ice Recrystallization Inhibition,” Langmuir, 2018, 34(17):5116-5123. [cited by applicant]
Weng et al., “Role of synthetic antifreeze agents in catalyzing ice nucleation,” Cryobiology, 2018, 84:91-94. [cited by applicant]
Wolanczyk et al., “Ice nucleating activity in the blood of the freeze-tolerant frog, Rana sylvatica,” Cryobiology, 1990, 27:328-335. [cited by applicant]
Wong et al., “The Role of Physical Stabilization in Whole Blood Preservation,” Scientific Reports, Feb. 2016, 6: 21023. [cited by applicant]
Wowk and Fahy, “Inhibition of bacterial ice nucleation by polyglycerol polymers,” Cryobiology, 2002, 44(1):14-23. [cited by applicant]
Wowk et al., “Vitrification enhancement by synthetic ice blocking agents,” Cryobiology, 2000, 40(3):228-236. [cited by applicant]
Xu et al., “Modulating TRADD to restore cellular homeostasis and inhibit apoptosis,” Nature, 2020, 587:133-138, 36 pages. [cited by applicant]
Yamada et al., “Tolerance in xenotransplantation,” Curr. Op. Organ Transplant., 2017, 22(6):522-528, 7 pages. [cited by applicant]
Yeh and Uygun, “Increasing donor liver utilization through machine perfusion,” Hepatology, 2019, 70:431-433, 6 pages. [cited by applicant]
Young et al., “Gene ontology analysis for RNAseq: accounting for selection bias,” Genome Biol., 2010, 11(2):R14, 12 pages. [cited by applicant]
Yu et al., “Circulating tumor cells: approaches to isolation and characterization,” J Cell Biol., Feb. 2011, 192(3):373-82. [cited by applicant]
Yu et al., “Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility,” Science, Jul. 2014, 345(6193):216-20. [cited by applicant]
Zachariassen and Kristiansen, “Ice Nucleation and Antinucleation in Nature,” Cryobiology, 2000, 41(4):257-279. [cited by applicant]
Zhai et al., “Ischaemia-reperfusion injury in liver transplantation-from bench to bedside,” Nat. Rev. Gastroenterol. Hepatol., 2013, 10(2):79-89. [cited by applicant]
Zhu et al., “A microdevice for multiplexed detection oft-cell-secreted cytokines,” Lab on a Chip, 2008, 8(12):2197-2205. [cited by applicant]
Zhu et al., “Lysosomal quality control of cell fate: a novel therapeutic target for human diseases,” Cell Death Dis., 2020, 11(9):817, 13 pages. [cited by applicant]
Arikura et al., “Abstract: UW Solution: A Promising Tool for Cryopreservation of Primarily Isolated Rat Hepatocytes,” J. Hepatobiliary. Pancreat. Surg., 2002, 9(6):742-749, 1 page. [cited by applicant]
Baust et al., “Cryopreservation: An Emerging Paradigm Change,” Organogenesis, 2009, 5(3):90-96. [cited by applicant]
Carpentier et al., “Abstract: Artificial and Bioartificial Liver Devices: Present and Future,” Gut, 2009, 58(12):1690-1702, 1 page. [cited by applicant]
De Vries et al., “Bulk Droplet Vitrification: An Approach to Improve Large-Scale Hepatocyte Cryopreservation Outcome,” Langmuir, 2019, 35(23):7354-7363. [cited by applicant]
Demetriou et al., “Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure,” Ann. Surg., 2004, 239(5):660-667. [cited by applicant]
Demirci and Montesano, “Abstract: Cell Encapsulating Droplet Vitrification,” Lab Chip, 2007, 7(11):1428, 5 pages. [cited by applicant]
Dou et al., “High Throughput Cryopreservation of Cells by Rapid Freezing of Sub-M1 Drops Using Inkjet Printing—Cryoprinting,” Lab Chip, 2015, 15(17):3503-3513, 11 pages. [cited by applicant]
Dunn et al., “Abstract: Hepatocyte Function and Extracellular Matrix Geometry: Long-Term Culture in a Sandwich Configuration,” FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 1989, 3(2):174-177, 1 page. [cited by applicant]
Dunn et al., “Abstract: Long-Term in Vitro Function of Adult Hepatocytes in a Collagen Sandwich Configuration,” Biotechnol. Prog., 1991, 7(3):237-245, 1 page. [cited by applicant]
El Assal et al., “Bio-Inspired Cryo-Ink Preserves Red Blood Cell Phenotype and Function During Nanoliter Vitrification,” Adv. Mater., 2014, 26(33):5815-5822. [cited by applicant]
Fitzpatrick et al., “Human Hepatocyte Transplantation: State of the Art,” J. Intern. Med., 2009, 266(4):339-357. [cited by applicant]
Fox and Chowdhury, “Hepatocyte Transplantation,” Am. J. Transplant., 2004, 4(Suppl 6):7-13. [cited by applicant]
Guillouzo et al., “Abstract: Survival and Function of Isolated Hepatocytes after Cryopreservation,” Chem. Biol. Interact., 1999, 121(1):7-16, 1 page. [cited by applicant]
Haridass et al., “Abstract: Hepatocyte Transplantation: Waiting for Stem Cells,” Curr. Opin. Organ Transplant., 2008, 13(6):627-632, 1 page. [cited by applicant]
He et al., “Vitrification by Ultra-Fast Cooling at a Low Concentration of Cryoprotectants in a Quartz Micro-Capillary: A Study Using Murine Embryonic Stem Cells,” Cryobiology, 2008, 56(3):223-232, 11 pages. [cited by applicant]
Heo et al., “‘Universal’ vitrification of Cells by Ultra-Fast Cooling,” Technology, 2015, 3(1):64-71, 9 pages. [cited by applicant]
Hopkins et al., “Effect of Common Cryoprotectants on Critical Warming Rates and Ice Formation in Aqueous Solutions,” Cryobiology, 2012, 65(3):169-178, 13 pages. [cited by applicant]
Hughes et al., “Current Status of Hepatocyte Transplantation,” Transplantation, 2012, 93(4):342-347. [cited by applicant]
International Preliminary Report in Patentability in International Appln. No. PCT/US2019/064026, mailed on Feb. 17, 2022, 8 pages. [cited by applicant]
International Search Report and Written Opinion in International Appln. No. PCT/US2019/064026, mailed on Apr. 21, 2020, 11 pages. [cited by applicant]
Invitation to Pay Additional Fees And, Where Applicable, Protest Fee in International Appln. No. PCT/US2019/064026, mailed on Feb. 3, 2020, 2 pages. [cited by applicant]
Jitraruch et al., “Cryopreservation of Hepatocyte Microbeads for Clinical Transplantation,” Cell Transplant., 2017, 26(8):1341-1354. [cited by applicant]
Kedem and Katchalsky, “Abstract: Thermodynamic Analysis of the Permeability of Biological Membranes to Non-Electrolytes,” Biochim. Biophys. Acta, 1958, 27(2):229-246, 4 pages. [cited by applicant]
Kuwayama, “Abstract: Highly Efficient Vitrification for Cryopreservation of Human Oocytes and Embryos: The Cryotop Method,” Theriogenology, 2007, 67(1):73-80, 1 page. [cited by applicant]
Manuchehrabadi et al., “Improved Tissue Cryopreservation Using Inductive Heating of Magnetic Nanoparticles,” Sci. Transl. Med., 2017, 9(379):eaah4586, 10 pages. [cited by applicant]
Ott et al., “Perfusion-Decellularized Matrix: Using Nature's Platform to Engineer a Bioartificial Heart,” Nat. Med., 2008, 14(2):213-221, 9 pages. [cited by applicant]
Parmegiani et al., “Sterilization of Liquid Nitrogen with Ultraviolet Irradiation for Safe Vitrification of Human Oocytes or Embryos,” Fertil. Steril., 2010, 94(4):1525-1528. [cited by applicant]
Petersen et al., “Tissue-Engineered Lungs for in Vivo Implantation,” Science, 2010, 329(5991):538-541. [cited by applicant]
Pless, “Artificial and Bioartificial Liver Support,” Organogenesis, 2007, 3(1):20-24. [cited by applicant]