IP Library › Granted Patent US 12,667,593
Granted Patent B2
US 12,667,593 · App. 17/770,018 · Granted Jun 30, 2026

Processes and apparatuses for obtaining amniotic mesenchymal stem cells from amniotic fluid and cells derived thereof

Inventors: Jan Talts (Staffanstorp, SE); Niels-Bjarne Woods (Furulund, SE); Kare Engkilde (Værløse, DK); Marcus Larsson (Bjärred, SE)
Assignee: Amniotics AB
A61K35/28A61K35/50A61P11/00C12N5/0668
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Quick Facts
Patent No.
US 12,667,593
App. No.
17/770,018
Filed
Apr 18, 2022
Granted
Jun 30, 2026
Kind
B2
Art Unit
1634
USPC
435/366
Abstract

Methods for purifying, culturing and selecting mesenchymal stem cell (MSC) subpopulations with neonatal quality and adult tissue specificity that are for use in production of advanced therapeutic medicinal products.

Claims (8)

1 . A method for obtaining term amniotic fluid lung mesenchymal stem cells (TAF lung MSCs) from term amniotic fluid, comprising:

providing term amniotic fluid (TAF);

removing particulate material from the TAF to obtain purified TAF cells;

performing adherence selection on the purified TAF cells to obtain TAF adherence cells;

passaging the TAF adherence cells to obtain a population of cells comprising the lung TAF MSCs; and

selecting the TAF lung MSCs from the population as cells that express Group B surface markers DDR1, CD248 and LRRC38, thereby obtaining TAF lung mesenchymal stem cells.

2 . The method of claim 1 , wherein selecting lung TAF MSCs further comprises excluding MSCs that express a marker selected from the group consisting of CD24, ITGB4, TNFSF10, GFRA1, CD74, FGFR4, HAVCR1, and OSCAR.

3 . The method of claim 1 , wherein the selecting step further comprises selecting TAF MSCs that further express at least another B surface marker selected from the group consisting of PCDH19, MME, IFITM10, BGN, NOTCH3, SULF1, TNFSF18, BDKRB1, FLT1, PDGFRA, TNFSF4, UNC5B, FAP, CASP1, DDR2, PCDH18 and CRLF1.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 29, 2022
From: TALTS, JAN; WOODS, NILS-BJARNE; ENGKILDE, KÅRE; LARSSON, MARCUS
To: AMNIOTICS AB
Reel/Frame 059716/0508 →
Priority Claims (3)
SE 1930338-7 · Oct 18, 2019 · national
SE 2030100-8 · Mar 26, 2020 · national
SE 2030101-6 · Mar 26, 2020 · national
Continuity (2)
Provisional Application 62923187 · Oct 18, 2019
Related Publication 20220372444A1 · Nov 24, 2022
References Cited (294)
US 4308875A · Young · 1982 [cited by applicant]
US 4567882A · Heller · 1986 [cited by applicant]
US 4787894A · Turnbull · 1988 [cited by applicant]
US 5019039A · Anderson · 1991 [cited by applicant]
US 5048530A · Hurwitz · 1991 [cited by applicant]
US 5100387A · Ng · 1992 [cited by applicant]
US 5137031A · Guirguis · 1992 [cited by applicant]
US 5395379A · Deutchman et al. · 1995 [cited by applicant]
US 5494044A · Sundberg · 1996 [cited by applicant]
US 5713351A · Billings et al. · 1998 [cited by applicant]
US 5772644A · Bark et al. · 1998 [cited by applicant]
US 5951497A · Wallace et al. · 1999 [cited by applicant]
US 6296764B1 · Guirguis et al. · 2001 [cited by applicant]
US 6378523B1 · Christopher · 2002 [cited by applicant]
US 6461628B1 · Blanchard et al. · 2002 [cited by applicant]
US 6479064B1 · Atala · 2002 [cited by applicant]
US 6506574B1 · Rambhatla et al. · 2003 [cited by applicant]
US 6733433B1 · Fell · 2004 [cited by applicant]
US 7255879B2 · Hariri · 2007 [cited by applicant]
US 7311905B2 · Hariri · 2007 [cited by applicant]
US 7596385B2 · Aghvami et al. · 2009 [cited by applicant]
US 7638141B2 · Hariri · 2009 [cited by applicant]
US 7682803B2 · Paludan et al. · 2010 [cited by applicant]
US 7802574B2 · Schultz · 2010 [cited by applicant]
US 7914779B2 · Hariri · 2011 [cited by applicant]
US 8987203B2 · Van Leeuwen et al. · 2015 [cited by applicant]
US 9783610B2 · Coukos et al. · 2017 [cited by applicant]
US 9868939B2 · Slukvin et al. · 2018 [cited by applicant]
US 10073096B2 · Lakshmipathy et al. · 2018 [cited by applicant]
US 10143448B2 · Brunner · 2018 [cited by applicant]
US 10201620B2 · Meis et al. · 2019 [cited by applicant]
US 10731132B2 · Larsson et al. · 2020 [cited by applicant]
US 10983123B2 · Lakshmipathy et al. · 2021 [cited by applicant]
US 11446334B2 · Talts et al. · 2022 [cited by applicant]
US 11542473B2 · Saxena et al. · 2023 [cited by applicant]
US 20050042595A1 · Haas · 2005 [cited by applicant]
US 20050054093A1 · Haas · 2005 [cited by applicant]
US 20050059152A1 · Tanavde et al. · 2005 [cited by applicant]
US 20050124003A1 · Atala et al. · 2005 [cited by applicant]
US 20050148074A1 · Davies et al. · 2005 [cited by applicant]
US 20070122903A1 · Rezania et al. · 2007 [cited by applicant]
US 20070134210A1 · Heidaran · 2007 [cited by applicant]
US 20070243172A1 · Ra et al. · 2007 [cited by applicant]
US 20070298497A1 · Antwiler · 2007 [cited by applicant]
US 20080064098A1 · Allickson · 2008 [cited by applicant]
US 20090191159A1 · Sakurada et al. · 2009 [cited by applicant]
US 20100113327A1 · Van Leeuwen et al. · 2010 [cited by applicant]
US 20100124569A1 · Abbot et al. · 2010 [cited by applicant]
US 20100136679A1 · Min et al. · 2010 [cited by applicant]
US 20100260815A1 · Kyle et al. · 2010 [cited by applicant]
US 20100323441A1 · Maggi et al. · 2010 [cited by applicant]
US 20100323446A1 · Barnett et al. · 2010 [cited by applicant]
US 20110184315A1 · Chen et al. · 2011 [cited by applicant]
US 20110256110A1 · Perin et al. · 2011 [cited by applicant]
US 20120107799A1 · Daum · 2012 [cited by applicant]
US 20120142102A1 · Chen et al. · 2012 [cited by applicant]
US 20120190731A1 · Messina · 2012 [cited by applicant]
US 20130157353A1 · Dijkhuizen Borgart et al. · 2013 [cited by applicant]
US 20130165816A1 · Mor · 2013 [cited by applicant]
US 20130171110A1 · Woods et al. · 2013 [cited by applicant]
US 20140038291A1 · Ahlfors et al. · 2014 [cited by applicant]
US 20140369968A1 · Slukvin et al. · 2014 [cited by applicant]
US 20150025366A1 · Harrell · 2015 [cited by applicant]
US 20150247852A1 · Lakshmipathy et al. · 2015 [cited by applicant]
US 20150250824A1 · Ma · 2015 [cited by applicant]
US 20150300939A1 · Ma · 2015 [cited by applicant]
US 20160030489A1 · Larsson et al. · 2016 [cited by applicant]
US 20160068815A1 · Larsson et al. · 2016 [cited by applicant]
US 20160199413A1 · Simonson et al. · 2016 [cited by applicant]
US 20170273670A1 · Rostaing et al. · 2017 [cited by applicant]
US 20170311934A1 · Brunner · 2017 [cited by applicant]
US 20180059109A1 · Hsuan et al. · 2018 [cited by applicant]
US 20180119104A1 · Slukvin et al. · 2018 [cited by applicant]
US 20180250343A1 · Reems et al. · 2018 [cited by applicant]
US 20180320137A1 · Valamehr et al. · 2018 [cited by applicant]
US 20190064164A1 · Lakshmipathy et al. · 2019 [cited by applicant]
US 20200048609A1 · Saxena et al. · 2020 [cited by applicant]
US 20200056156A1 · Ino et al. · 2020 [cited by applicant]
US 20200095551A1 · Woods et al. · 2020 [cited by applicant]
US 20200171097A1 · Larsson et al. · 2020 [cited by applicant]
US 20210060084A1 · Harrell · 2021 [cited by applicant]
US 20220145250A1 · Talts et al. · 2022 [cited by applicant]
US 20220297032A1 · Talts et al. · 2022 [cited by applicant]
US 20220348876A1 · Woods et al. · 2022 [cited by applicant]
US 20230000922A1 · Talts et al. · 2023 [cited by applicant]
US 20230340415A1 · Saxena et al. · 2023 [cited by applicant]
US 20240164369A1 · Engkilde et al. · 2024 [cited by applicant]
US 20240165164A1 · Talts et al. · 2024 [cited by applicant]
US 20240165311A1 · Larsson et al. · 2024 [cited by applicant]
US 20250129334A1 · Woods · 2025 [cited by applicant]
AU 2013204820 · 2013 [cited by applicant]
AU 2013204968 · 2014 [cited by applicant]
AU 2014201181 · 2014 [cited by applicant]
CN 1407088 · 2003 [cited by applicant]
CN 101418284A · 2009 [cited by applicant]
CN 102549169 · 2012 [cited by applicant]
CN 202569006 · 2012 [cited by applicant]
CN 202723948 · 2013 [cited by applicant]
CN 109777773A · 2019 [cited by applicant]
CN 109971709A · 2019 [cited by applicant]
DE 202004012970 · 2005 [cited by applicant]
EP 1029228 · 2000 [cited by applicant]
EP 2302036 · 2011 [cited by applicant]
EP 2479261 · 2012 [cited by applicant]
EP 3029137 · 2019 [cited by applicant]
EP 3117828 · 2020 [cited by applicant]
JP 2005323534 · 2005 [cited by applicant]
JP 2010529851 · 2010 [cited by applicant]
JP 2010265220 · 2010 [cited by applicant]
JP 2011084566 · 2011 [cited by applicant]
JP 2012521780 · 2012 [cited by applicant]
JP 2012255025 · 2012 [cited by applicant]
WO WO0235992 · 2002 [cited by applicant]
WO WO03042405 · 2003 [cited by applicant]
WO WO03068937 · 2003 [cited by applicant]
WO WO05078073 · 2005 [cited by applicant]
WO WO06012404 · 2006 [cited by applicant]
WO WO2008060139 · 2008 [cited by applicant]
WO WO2009031818 · 2009 [cited by applicant]
WO WO2009052132 · 2009 [cited by applicant]
WO WO2009135206A1 · 2009 [cited by applicant]
WO WO10099539 · 2010 [cited by applicant]
WO WO2012021845 · 2012 [cited by applicant]
WO WO2012070032 · 2012 [cited by applicant]
WO WO2013082487 · 2013 [cited by applicant]
WO WO2014055121 · 2014 [cited by applicant]
WO WO2014089121A2 · 2014 [cited by applicant]
WO WO2014140913 · 2014 [cited by applicant]
WO WO2015016761 · 2015 [cited by applicant]
WO WO2015023720 · 2015 [cited by applicant]
WO WO2015073786 · 2015 [cited by applicant]
WO WO2016120310 · 2016 [cited by applicant]
WO WO2018073615 · 2018 [cited by applicant]
WO WO2018083700 · 2018 [cited by applicant]
WO WO2018148501 · 2018 [cited by applicant]
WO WO2018152364 · 2018 [cited by applicant]
WO WO2018169554 · 2018 [cited by applicant]
WO WO2018171947A1 · 2018 [cited by applicant]
WO WO2018185584 · 2018 [cited by applicant]
WO WO2018186421 · 2018 [cited by applicant]
WO WO2019035880 · 2019 [cited by applicant]
WO WO2019091478A1 · 2019 [cited by applicant]
WO WO2019104381A1 · 2019 [cited by applicant]
WO WO2019126748A1 · 2019 [cited by applicant]
WO WO2018221555 · 2020 [cited by applicant]
WO WO2021076042A2 · 2021 [cited by applicant]
WO WO2021087436 · 2021 [cited by applicant]
Kaltz et al. “Novel markers of mesenchymal stem cells definted by genome-wide gene expression analysis of stromal cells from different sources” (2010) Exp Cell Res, 316: 2609-2617. (Year: 2010). [cited by examiner]
International Search Report from PCT/SE2020/050994, dated Feb. 15, 2021 in 19 pages. [cited by applicant]
International Search Report from PCT/SE2020/050993 dated Apr. 15, 2021. [cited by applicant]
Allard et al., “Immunohistochemical Toolkit for Tracking and Quantifying Xenotransplanted Human Stem Cells.” Regenerative Medicine 9.4 (2014): 437-452. [cited by applicant]
Bossolasco et al., “Molecular and phenotypic characterization of human amniotic fluid cells and their differentiation potential”, Cell Research, 2006 16: pp. 329-336. [cited by applicant]
De Coppi, et al., “Isolation of Amniotic Stem Cell Lines with Potential for Therapy”. Nature Biotechnology vol. 25, No. 1 (2007) 100-106. [cited by applicant]
Djouad, et al., “Mesenchymal Stem Cells: Innovative Therapeutic Tools for Rheumatic Diseases.” Nature Reviews Rheumatology 5.7 (2009): 392-399. [cited by applicant]
Ge et al. “The Size of Mesenchymal Stem Cells is a Significant Cause of Vascular Obstructions and Stroke”. Stem Cell Reviews and Reports, Apr. 2014.10(2): 295-303. [cited by applicant]
Hamid et al., “Highly potent stem cells from full-term amniotic fluid: A realistic perspective” Reprod Biol, 2017, 17(1):9-18; whole document. [cited by applicant]
Han et al., “Genetically modified mesenchymal stem cell therapy for acute respiratory distress syndrome”, stem Cell Res Ther, 2019, 10(1 ):386; whole document. [cited by applicant]
Hoogduijn et al., “Morphology and Size of Stem Cells From Mouse and Whale: Observational Study.” Bmj 347 (2013). [cited by applicant]
Kim et al., “Time-course transcriptional profiling of human amniotic fluid-derived stem cells using microarray” Cancer Res Treat, 2010, 42(2):82-94; whole document. [cited by applicant]
Kuroda et al. “Treatment of A Full-Thickness Articular Cartilage Defect in the Femoral Condyle of an Athlete with Autologous Bone-Marrow Stromal Cells.” Osteoarthritis and Cartilage, vol. 15, No. 2 (2007): 226-231. [cited by applicant]
Lee et al., “Xenogeneic human umbilical cord-derived mesenchymal stem cells reduce mortality in rats with acute respiratory distress syndrome compl icated by sepsis”, Oncotarget, 2017, 8(28):45626-45642; whole document. [cited by applicant]
Lesage et al., “The amniotic fluid as a source of mesenchymal stem cells with lung-specific characteristics”, Wiley Prenatal Diagnosis 2017, pp. 1093-1099. [cited by applicant]
Leng et al., “Transplantation of ACE2—Mesenchymal stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia”, Aging Dis, Mar. 9, 2020, 11(2):216-228; whole document. [cited by applicant]
Moraghebi et al., “Term amniotic fluid: an unexploited reserve of mesenchymal stromal cells for reprogramming and potential cell therapy applications” Stem Cell Research & Therapy, 2017,8(1):190; whole document. [cited by applicant]
Pak, “Regeneration of Human Bones in Hip Osteonecrosis and Human Cartilage in Knee Osteoarthritis With Autologous Adipose-Tissue-Derived Stem Cells: A Case Series.” J Med Case Reports 5. 296 (2011). [cited by applicant]
Saguil et al., American Family Physician, 2012, vol. 85, No. 4, pp. 352-358, 2012. [cited by applicant]
Spitzhorn et al., “Isolation and Molecular Characterization of Amniotic Fluid-Derived Mesenchymal Stem Cells Obtained from Caesarean Sections”, Hindawi Stem Cells International, Volum 2017, Article ID 5932706, in 15 pag… [cited by applicant]
Vadasz et al., “Second and third trimester amniotic fluid mesenchymal stem cells canrepopulate a de-cellularized lung scaffold and express lung markers”, J Pediatr Surg, 2014, 49(11): 1554-63; whole document. [cited by applicant]
Vega, et al., 2017. “High-Content Image Informatics of the Structural Nuclear Protein NumaParses Trajectories for Stem/Progenitor Cell Lineages and Oncogenic Transformation”. Exp. Cell Res. 351:11-23. [cited by applicant]
Zhou et al., “Amniotic fluid-derived mesenchymal stem cells: characteristics and therapeutic applications” Arch Gynecol Obstet, 2014, 290(2):223-231; whole document. [cited by applicant]
Brett et al., “Isolation of CD248-expressing stromal vascular fraction for targeted improvement of wound healing”, 2017, doi: 10.1111/wrr.12542. [cited by applicant]
Brett, E. et al., “Isolation of CD248-expressing stromal vascular fraction for targeted improvement of wound healing”, Accepted Article, doi: 10.1111/wrr.12542. [cited by applicant]
Enes, S.R. et al., “MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC”, Scientific Reports, 2016, vol. 6, No. 1. [cited by applicant]
Macfadyen, J.R. et al., “Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumor endothelium”, FEBS Letters 579 (2005) 2569-2575. [cited by applicant]
Anker et al., “Isolation of Mesenchymal Stem Cells of Fetal or Maternal Origin from Human Placenta,” Stem Cells, vol. 22, 2004, p. 1338-1345. [cited by applicant]
Bar-Nur et al., “Epigenetic Memory and Preferential Lineage-Specific Defferentation in Induced Pluripotent Stem Clles Derived from Human Pancreatic Isley Bets Cells”, Cell Stem Cell vol. 9, No. 1, 2011, pp. 17-23. [cited by applicant]
Bieback et al., “Clinical Protocols foe the Isolation and Expansion of Mesenchymal Stromal Cells”, Transfucion Medicine and Hemotherapy, 2008, vol. 35, pp. 286-294. (Year: 2008). [cited by applicant]
Bongso et al., “Taking Stem Cells to the Clinic: Major Challenges,” Journal of Cellular Biochemisty, vol. 105, 2008, p. 1352-1360. [cited by applicant]
Bottai et al., “Third trimester amniotic fluid cells with the capacity to develop neural phenotypes and with heterogeneity among sub-populations,” Restorative Neurology and Neuroscience, vol. 30, 2012, p. 55-68. [cited by applicant]
Cao et al., Stem Cell Repair of Central Nervous System Injury Neuroscience Res vol. 68, 2002, pp. 501-510. [cited by applicant]
Carette et al., “Generation of iPSCs from cultured human malignant cells”, Blood, vol. 115, No. 20, 2010, pp. 4039-4042. [cited by applicant]
Chanda et al., “Retinoic Acid Signaling is Essential for Embryonic Hematopoietic Stem Cell Development”, Cell, vol. 155, No. 1, Sep. 26, 2013, pp. 215-227, XP028729738, ISSN: 0092-8674, DOI: 10.1016/J.CELL.2013.08.055. [cited by applicant]
Cipolleschi et al (“The Role of Hypoxia in the Maintenance of Hematopoietic Stem Cells,” Blood, vol. 82, No. 7 (Oct. 1, 1993: pp. 2031-2037). [cited by applicant]
Dewar et al. “Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors” Leukemia (2003) vol. 17 pp. 1713-1721. [cited by applicant]
De Wynter et al., “Comparison of Purity and Enrichment of CD34 + Cells from Bone marrow, Umbilical Cord and Peripheral Blood (primed for Apheresis) Using Five Separation Systems”, Stem Cells, 1995, vol. 13, pp. 524-532. [cited by applicant]
Dobreva et al., “On the origin of amniotic stem cells: of mice and men,” The International Journal of Developmental Biology, vol. 54, 2010, p. 761-777. [cited by applicant]
Eggerman J et al.,“Endothelial progenitor cell culture and differentiation in vitro: a methodological comparison using human umbilical cord blood”, Cardiovascular Research, Oxford University Press, GB, vol. 58, No. 2, M… [cited by applicant]
Flow Rate Units Conversion, Traditional Oven, 5 pages, retrieved from the internet (5/0/2022): https://www.traditionaloven.com/ tutorials/flow-rate/convert-gtt-drop-per-minute-to-ml-milliliter-per-hour.html (Year: 2022). [cited by applicant]
Forman et al., Reactive Oxygen Species and Cell Signaling, Respiratory Burst in Macrophage Signaling vol. 166 pp. 54-58, 2002. [cited by applicant]
Forraz et al., “The umbilical cord: a rich and ethical stem cell source to advance regenerative Medicine,” Cell Proliferation, vol. 44, 2011, p. 60-69. [cited by applicant]
Friedman et al., “Umbilical Cord Mesenchymal Stem Cells: Adjuvants for Human Cell Transplantation,” American Society for Blood and Marrow Transplantation, vol. 13, 2007, p. 1477-1486. [cited by applicant]
Goichberg et al., “CAMP-induced PKC activation increases functional CXCR4 expression on human CD34+ hematopoietic progenitors” BLOOD, vol. 107, No. 3, Feb. 1, 2006. [cited by applicant]
Ghosh et al., “Persistnat Donor Cell Gene Expression among Human Induced Pluripotent Stem Cells Contributes to Differences with Human Embryonic Stem Cells”, Plos One, vol. 5, No. 2, 2010, p. E8975. [cited by applicant]
Halliwell, “Cell Culture, Oxidative Stress, and Antioxidants: Avoiding Pitfalls”, Biomed J. vol. 37, No. 3, May-Jun. 2014. [cited by applicant]
Hanna et al., “Direct cell reprogramming is a stochastic process amenable to acceleration”., Nature vol. 462, No. 7273, 2009, pp. 595-601. [cited by applicant]
Hong, D.K., et al., “Combined treatment with Dichloroacetic acid and pyruvate reduces hippocampal neuronal death after transient cerebral ischemia,” Frontiers in Neurology, Mar. 2018, vol. 9, Article 137 (in 11 pages). [cited by applicant]
Iizuka, H., et al., “Targeted gene correction of RUNX1 in induced pluripotent stem cells derived from familial platelet disorder with propensity to myeloid malignancy restores normal megakaryopoiesis,” Experimental Hema… [cited by applicant]
Ikehata et al.“Environmenatal Molecular Mutagenesis”, vol. 41, No. 4, 2003, pp. 280-292. [cited by applicant]
Ikehata et al.,“Mutation spectrum in sunlight-exposed”, vol. 556, No. 1-2, 2004, pp. 11-24. [cited by applicant]
Ingram D A et al., “Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood”, Blood, American Society of Hematology, US, vol. 104, No. 9, Nov. 1, 2004 (Nov. 1,… [cited by applicant]
Kim et al.,“Epigenetic memory in induced pluripotent stem cells”, vol. 467, No. 7313, 2010, pp. 285-290. [cited by applicant]
Kettle et al (“Mechanism of inactivation of myeloperoxidase by 4-aminobenzoic acid hydrazide,” Biochem. J. (1997) 321, 503-508). [cited by applicant]
Kinney, M.A., et al., “A systems biology pipeline identifies regulatory networks for stem cell engineering,” Nature Biotechnology, 2019, vol. 37, pp. 810-818. [cited by applicant]
Kumano et al., “Generation of Induced pluripotent stem cells from primaty chronic myelogenous leukemia patient samples”, Blood vol. 119, No. 26, 2012, pp. 6234-6242. [cited by applicant]
Lee et al., “Derivation of neural crest cells from human pluripotent stem cells”. Nature protocols 5:88-701 (2010). [cited by applicant]
Li, Yaqing, et al., “Therapeutic effects of amniotic fluid-derived mesenchymal stromal cells on lung injury in rats with emphysema,” Respiratory Research (2014) 15:120. [cited by applicant]
Lindencrona et al., “CD4+ T Cell-Mediated Her-2/Neu-Specific Tunor Rejection in the Absence of B Cells”., Int J Cancer vol. 109, 2004, pp. 259-264. [cited by applicant]
Lith et al (“Engineering biodegradable polyester elastomers with antioxidant properties to attenuate oxidative stress in tissue,” Biomaterials. Sep. 2014 ; 35(28): 8113-8122). [cited by applicant]
L. M. Reid, “Stem cell biology, hoemone/matrix synergies and liver differentiation”. Current Opinion in Cell Biology, vol. 2, 1990, p. 121-130. [cited by applicant]
Ma, Q-S., et al., “Ligand-based design, synthesis and biological evaluation of xanthine derivatives as LSD1/KDM1A inhibitors,” European Journal of Medicinal Chemistry, 2018, vol. 162, pp. 555-567 (Accepted Manuscript). [cited by applicant]
Marchetto et al., “Transcriptional Signature and Memory Retention of Human-Induced Pluripotent Stem Cells”. Plos One vol. 4, No. 9, 2009, p. E7076. [cited by applicant]
Masip et al., “Reprogramming with defined factors: from induced pluripotency to induced transdifferentiation”., Molecular Human Reproduction, vol. 16, No. 11 pp. 856-868, 2010. [cited by applicant]
Melissa Ann Brown et al., “Umbilical Cord Blood Derived Endothelial Progenitor Cells: Isolation, Characterization, and Adhesion Potential in Vitro and in Vivo”,, Jan. 1, 2009 (Jan. 1, 2009), XP055140385, Retrieved from … [cited by applicant]
Mareschi et al., “Multipotent Mesenchymal Stromal Stem Cell Expansion by Plating Whole Bone Marrow at a Low Cellular Density: A More Advantageous Method for Clinical Use”, Stem Cells International, 2012, vol. 2012, pp. … [cited by applicant]
Maurice et al., “Isolation of progenitor cells from cord blood using adhesion matrices”, Cytotechnology, 2007, vol. 54, pp. 121-133. [cited by applicant]
McGuckin et al., “Culture of embryonic-like stem cells from human umbilical cord blood and onward differentiation to neural cells in vitro,” Nature Protocols, vol. 3, 2008, p. 1046-1055. [cited by applicant]
Mizuno et al., “Generation of skeletal muscle stem/progenitor cells from murine induced pluripotent stem cells,” The Journal of the Federation of American Societies for Experimental Biology, vol. 24, 2010, p. 2245-2253. [cited by applicant]
Murphy et al., “Amnion Epithelial Cell Isolation and Characterization for Clinical Use,” Current Protocols in Stem Cell Biology, vol. 13, 2010, p. 1-25. [cited by applicant]
M. V. Wiles, Embryonic Stem Cell Differentiation in vitro Meth. EnzymoIL. vol. 225, 1993, p. 900. [cited by applicant]
Naik, P.O., et al., “Mitophagy-driven metabolic switch reprograms stem cell fate,” Cellular and Molecular Life Sciences, Sep. 28, 2018, vol. 76, pp. 27-43. [cited by applicant]
Nijboer et al (Targeting the p53 Pathway to Protect the Neonatal Ischemic Brain, Ann Neural 2011; 70:255-264). [cited by applicant]
Oburoglu, L., et al., “Glucose and Glutamine Metabolism Regulate Human Hematopoietic Stem Cell Lineage Specification,” Cell Stem Cell, 2014, vol. 15, pp. 169-184. [cited by applicant]
O'Donoghue et al., “Fetal stem cells,” Best Practice & Research Clinical Obstetrics and Gynaecology, vol. 18, No. 6, pp. 853-875, 2004. [cited by applicant]
Osanai et al., “Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin”., vol. 44, No. 4, 2011, pp. 200-206. [cited by applicant]
Okabe et al., “Definitive proof for direct reprogramming of hematopoietic cells to pluripotency”, Blood, 2009, vol. 114, No. 9, pp. 1764-1767. [cited by applicant]
Panopoulos et al., “Rapid and Highly Efficient Generation of Induced Pluripotent Stem Cells from Human Umbilical Vein Endothelial Cells”, PLOS ONE, vol. 6, No. 5, May 16, 2011 (May 16, 2011), p. e19743, XP055035699, DOI… [cited by applicant]
Park et al., “Disease-Specific Induced Pluripotent Stem Cells”., Cell vol. 134, No. 5, 2008, pp. 877-886. [cited by applicant]
Pereira et al., “Reproducible methodology for the isolation of mesenchymal stem cells from human umbilical cord and its potential for cardiomyocyte generation,” Journal of Tissue Engineering and Regenerative Medicine, v… [cited by applicant]
Pelus, L.M., et al., “Peripheral Blood Stem Cell Mobilization: a Look Ahead,” Current Stem Cell Reports, 2018, vol. 4, pp. 273-281. [cited by applicant]
Phuc et al., “Isolation of three important types of stem cells from the same samples of banked umbilical cord blood”, Cell Tissue Bank, published online Jun. 8, 2011, vol. 13, pp. 341-351. [cited by applicant]
Polo et al., “Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells”., Nature Biotechnology, vol. 28, No. 8, 2010, pp. 848-855. [cited by applicant]
P.D. Rathjen et al., “Properies and uses of Embryonic Stem Cells Prospects for Application to Human Biology and Gene Therapy” Reprod. Fertil. Dev. vol. 10, 1998, p. 31. [cited by applicant]
Prigione et al (“The Senescence-Related Mitochondrial/Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells,” Stem Cells 2010;28:721-733). [cited by applicant]
Ronn et al., Reactive Oxygen Species Impair the Function of CD90+ Hematopoietic Progenitors Generated from Human Pluripotent Stem Cells. Sep. 1, 2016, vol. 35, No. 1; pp. 197-206; p. 2, 1 [cited by applicant]
Ronn et al., “Retinoic Acid Regulates Hematopoietic Development from Human Pluripotent Development from Human Pluripotent Stem Cells”, Stem Cell Reports, vol. 4, No. 2, Feb. 1, 2015, pp. 269-281, XP055333217, United Sta… [cited by applicant]
Robertson, “Teratocarcinomas and embryonic stem cells: A practical approach”, 1987, IRL Press Ltd. [cited by applicant]
Roubelakis, M.G., et al., “In vitro and in vivo properties of distinct populations of amniotic fluid mesenchymal progenitor cells,” Journal of Cellular and Molecular Medicine, vol. 15, 2011, p. 1896-1913. [cited by applicant]
Salehinejad et al., “Comparison of different methods for the isolation of mesenchymal stem cells from human umbilical cord Wharton's jelly,” In Vitro Cell.Dev.Biol.—Animal (2012) 48:75-83. [cited by applicant]
Saxena et al., “Cyclic AMP Signaling through Epac Axis Modulates Human Hemogenic Endothelium and Enhances Hematopoietic Cell Generation”, Stem Cell Reports, vol. 6, No. 5, May 1, 2016, pp. 692-703, XP055333169, United S… [cited by applicant]
Savickiene et al., “Human Amniotic Fluid Mesenchymal Stem Cells from Second- and Third-Trimester Amniocentesis: Differentiation Potential, Molecular Signature, and Proteome Analysis,” Stem Cells International, 2015, in … [cited by applicant]
Schiavo, A.A., et al., “Endothelial properties of third-trimester amniotic fluid stem cells cultured in hypoxia,” Stem Cell Research & Therapy, (2015) 6:209, p. 1-15. [cited by applicant]
Seshareddy et al. “Method to Isolate Mesenchymal-Like Cells from Wharton's Jelly of Umbilical Cord,” Methods in Cell Biology, vol. 86, 2008, p. 101-119. [cited by applicant]
Shigemura, T., et al., “Mosaicism of an ELANE mutation in an asymptomatic mother,” Journal of Clinical Immunology, Jan. 2019, vol. 39, pp. 106-111. [cited by applicant]
Suzuki, H., et al., “Glycolytic pathway affects differentiation of human monocytes to regulatory macrophages,” Immunology Letters 176: 18-27 (2016), Accepted Manuscript. [cited by applicant]
Takahashi et al., “Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors”., Cell vol. 126, No. 4, 2006, pp. 663-676. [cited by applicant]
Uchida, N., et al., “Efficient generation of b-globin-expressing erythroid cells using stromal cell-derived induced pluripotent stem cells from patients with sickle cell disease,” Stem Cells, 2017, vol. 33, pp. 586-596. [cited by applicant]
Vodyanik, M.A., et al., “Leukosialin (CD53) defines hematopoietic progenitors in human embryonic stem cell differentiation cultures,” Blood, 2006, vol. 108, pp. 2095-2105. [cited by applicant]
Vizcardo et al. “Regeneration of Human Tumor Anitigen-Specific T Cells from iPSCs Devrived from Mature CD8 T Cells”, Cell Stem Cell, Jan. 3, 2013, vol. 12, No. 1, pp. 31-36. [cited by applicant]
Wang et al (“Calpain inhibitor attenuates ER stress-induced apoptosis in injured spinal cord after bone mesenchymal stem cells X transplantation,” Neurochemistry International 97: 15-25 (Jul. 2016). [cited by applicant]
Wassarman et al., “Guide to Techniques in Mouse Development”, Methods in Enzymology vol. 225, 1993. [cited by applicant]
Weiss et al., “Stem Cells in the Umbilical Cord,” Stem Cell Review, vol. 2, 2006, p. 155-162. [cited by applicant]
Wilson, Jennifer G., et al., “Mesenchymal Stem (Stromal) Cells for Treatment of Ards: A Phase 1 Clinical Trial”, Lancet Respir Med. Jan. 2015; 3(1): 24-32. [cited by applicant]
Wisniewski et al. (Further phenotypic characterization of the primitive lineage-CD34+CD38−CD90+CD45Ra-hematopoietic stem cell/progenitor cell sub-population isolated from cord blood, mobilized peripheral blood and patie… [cited by applicant]
You, Q., et al., “Isolation of human mesenchymal stem cells from third-trimester amniotic fluid,” International Journal of Gynecology and Obstetrics, vol. 103, 2008, p. 149-152. [cited by applicant]
Ye et al., “Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders”., Blood vol. 114, No. 27, 2009, pp. 5473-5480. [cited by applicant]
Yu et al., “Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells”., Science vol. 318, No. 5858, 2007, pp. 1917-1920. [cited by applicant]
Zhou et al., “Generation of human induced pluripotent stem cells from urine samples,” Nature Protocols, vol. 7, 2012, p. 2080-2089. [cited by applicant]
International Search Report and Written Opinion for PCT/US2017/023090 dated Aug. 15, 2017 in 16 pages. [cited by applicant]
International Search Report and Written Opinion for PCT/IB2016/001628 dated Jan. 24, 2017 in 14 pages. [cited by applicant]
International Search Report in PCT/SE2020/050631, issued Oct. 9, 2020. [cited by applicant]
International Search Report in PCT/SE2020/051139 issued Jan. 28, 2021. [cited by applicant]
International Preliminary Report on Patentability and Written Opinion for PCT/IB2016/001628 dated May 2, 2019 in 8 pages. [cited by applicant]
International Preliminary Report on Patentability in PCT/SE2020/050631, mailed Sep. 17, 2021. [cited by applicant]
International Preliminary Report on Patentability and Written Opinion for PCT/US2017/023090 dated Sep. 26, 2019 in 7 pages. [cited by applicant]
Benedetto, P. D., et al. (2018). “Blocking CD248 molecules in perivascular stromal cells of patients with systemic sclerosis strongly inhibits their differentiation toward myofibroblasts and proliferation: A new potenti… [cited by applicant]
Bartis et al., “Role of CD248 as a potential severity marker in idiopathic pulmonary fibrosis”, BMC Pulmonary Medicine, vol. 16(51):1-10 (2016). [cited by applicant]
Baulier et al., “Amniotic fluid-derived mesenchymal stem cells prevent fibrosis and preserve renal function in a preclinical porcine model of kidney transplantation”, Stem Cells Translational Medicine, vol. 3(7):809-820… [cited by applicant]
Casada-Diaz et al., “Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing” Mar. 2020, vol. 8, Article 146 (in 3 parts). [cited by applicant]
Daley, “From embryos to embryoid bodies”, Ann. N. Y. Acad. Sci. vol. 996: 122-131 (2003). [cited by applicant]
Duffy et al., “Mesenchymal stem cells effects on T-cell effector pathways”, Stem Cell Research and Therapy, vol. 2(34):1-9 (2011). [cited by applicant]
Fraser et al., Immature monocytes from G-CSF-mobilized peripheral blood stem cell collections carry surface-bound IL-10 and have the potential to modulate alloreactivity< Journal of Leukocyte Biology, vol. 80:862-869 (2… [cited by applicant]
Gasmi et al., “Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis”, Archives of Toxicology, vol. 95:1161-1178 (2021). [cited by applicant]
Gu et al., “Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK”, Scientific Reports, vol. 5(733):1-11 (2015). [cited by applicant]
Hu Jiajia et al., “Exosomes derived from human amniotic fluid mesenchymal stem cells alleviate cardiac fibrosis via enhancing angiogenesis in vivo and in vitro”, Cardiovascular Diagnosis and Therapy, vol. {0} 11, No. {0… [cited by applicant]
Johannesson et al., “Extracellular vesicles derived from amniotic fluid mesenchymal stem cells selected by skin tissue type markers reduce inflammation”, Cytotherapy, available online Apr. 25, 2022, vol. 24, S89-S90. [cited by applicant]
Lee et al., “Allogenic human mesenchymal stem cells for treatment of [cited by applicant]
Lim et al., “Hematopoietic cell differentiation from embryonic and inducd pluripotent stem cells”, Stem Cell Research & Therapy, vol. 4:71 (2013). [cited by applicant]
Mareschi et al., “Immunoregulatory effects on T lymphocytes by human mesenchymal stromal cells isolated from bone marrow, amniotic fluid, and placenta”, Experimental Hematology, vol. 44:138-150 (2016). [cited by applicant]
Matsuhashi et al., “Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart”, Journal of Molecular and Cellular Cardiology, vol. 82:116-124 (2015). [cited by applicant]
Naylor et al., “The Mesenchymal Stem Cell Marker CD248 (Endosialin) is a negative regulator of bone formation in mice”, Arthritis Rheum, vol. 64(10:3334-3343 (2012). [cited by applicant]
O'Donoghue et al., “Amniocentesis in the third trimester of pregnancy”, Prenatal Diagnosis, vol. 27(11):1000-1004 (2007). [cited by applicant]
REDEYE Equity Research, “Amniotics,” Initiation of Coverage, 2021, Retrieved from the Internet, URL <https://s3-eu-west-1.amazonaws.com/rdey-cms-prod/app/uploads/2021/10/amniotics-initiation-of-coverage-1-1.pdf>; whole … [cited by applicant]
Spong, “Defining ‘term’ pregnancy recommendations from the defining ‘term’ pregnancy workgroup”, JAMA, vol. 309(23):2445-2446 (2013). [cited by applicant]
Takov Kaloyan et al., “Small extracellular vesicles secreted from human amniotic fluid mesenchymal stromal cells possess cardioprotective and promigratory potential”, Mar. 7, 2020 (Mar. 7, 2020), vol. {0} 115, No. {0} 3… [cited by applicant]
Teicher B. A. (2019) “CD248: A therapeutic target in cancer and fibrotic diseases”. Oncotarget. 10(9): 993-1009. [cited by applicant]
Tian, “Cytokine requierments differ for stroma and embryoid body-mediated hematopoiesis from human embryonic stem cells”, Experimental Hematology, vol. 32(10):1000-1009 (2004). [cited by applicant]
Wehrmann et al., “y8 T cells protect against LPS-induced lung injury”, Journal of Leukocyte Biology, vol. 99:373-386 (2016). [cited by applicant]
Zhao Xiangnan et al., “Chitosan hydrogel-loaded MSC-derived extracellular vesicles promote skin rejuvenation by ameliorating the senescence of dermal fibroblasts”, Mar. 20, 2021 (Mar. 20, 2021), vol. {0} 12, No. {0} 196… [cited by applicant]
International Search Report and Written Opinion in application No. PCT/EP2022/057249, mailed on Sep. 6, 2022, in 11 pages. [cited by applicant]
International Preliminary Report on Patentability and Written Opinion in application No. PCT/EP2022/057249, dated Sep. 12, 2023, in 7 pages. [cited by applicant]
Supplementary European Search Report in European Patent Appilcation No. 20825113.2, May 9, 2023, in 1 page. [cited by applicant]
Office Action received in corresponding Chinese Patent Application No. 202080083341.3 issued on May 4, 2023. [cited by applicant]
Chinese Search Report in Chinese Patent Application No. 202080083341.3, dated Apr. 2, 2023. [cited by applicant]
International Search Report issued in PCT/EP2023/061254 filed Apr. 28, 2023. [cited by applicant]