Granted Patent
E1
US 51,018 · App. 17/978,982 · Granted Sep 1, 2026
Modulation of splenocytes in cell therapy
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Abstract
The invention provides methods for treating pathological conditions associated with an undesirable inflammatory component. The invention is generally directed to reducing inflammation by administering cells that have one or more of the following effects in an injured subject: interact with splenocytes, preserve splenic mass, increase proliferation of CD4 + and CD8 + T-cells, increase IL-4 and IL-10, decrease IL-6 and IL-1β, and increase M2:M1 macrophage ratio at the site of injury. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to have these effects. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired potency for achieving these effects.
Claims (17)
1 . A method for obtaining cells that have the an ability to (1) preserve splenic mass in an injury, (2) increase splenocyte proliferation in the spleen, (3) increase T-regulatory cells; , (4) increase one or more of IL-10 and IL-4, or (5) decrease IL-2 6 and IL-1β, the method comprising:
obtaining non-embryonic non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of the endodermal, ectodermal, or mesodermal germ layers;
administering the non-embryonic non-germ cells to a subject;
assaying the non-embryonic non-germ cells for said ability by performing one or more of: (1) an assay of splenic mass in an injury, (2) an assay of splenocyte proliferation in the spleen, (3) an assay of T-regulatory cells, (4) an assay of IL-10 and IL-4, and or (5) an assay of IL-2 6 and IL-1β, wherein said cells that are assayed are non-embryonic non-germ cells that express one or more of oct4, telomerase rex-1 or rox-1 and/or can differentiate into cell types of at least two of the endodermal, ectodermal, and mesodermal germ layers ; and
obtaining one or more non-embryonic non-germ cells that have said ability.
2 . The method of claim 1 wherein the non-embryonic non-germ cells express telomerase.
3 . The method of claim 1 wherein the non-embryonic non-germ cells express oct4.
4 . The method of claim 1 wherein the non-embryonic non-germ cells express oct4 and telomerase.
5 . The method of claim 1 wherein the non-embryonic non-germ cells can differentiate into cell types of at least two of the endodermal, ectodermal, and mesodermal germ layers.
6 . The method of claim 1 wherein the non-embryonic non-germ cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers.
7 . The method of claim 1 wherein the non-embryonic non-germ cells express oct4 and telomerase and can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers.
8 . The method of claim 1 wherein the non-embryonic non-germ cells can differentiate into cell types of endodermal, ectodermal, and mesodermal germ layers and express telomerase and oct4.
9 . The method of claim 1 wherein the non-embryonic non-germ cells are human.
10 . The method of claim 1 wherein the non-embryonic non-germ cells are derived from bone marrow.
11. The method of claim 1 , further comprising selecting the one or more non-embryonic non-germ cells that have said ability for being banked in a cell bank.
12. The method of claim 11 , further comprising banking the selected one or more non-embryonic non-germ cells that have said ability in the cell bank.
13. The method of claim 1 , further comprising administering the one or more non-embryonic non-germ cells that have said ability to the subject.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 3, 2024
From: ABT HOLDING COMPANY; ATHERSYS, INC.; ADVANCED BIOTHERAPEUTICS, INC.; REGENESYS BVBA; REGENESYS, LLC
To: HEALIOS K.K.
Reel/Frame 067606/0139 →
RELEASE OF SECURITY INTEREST
Recorded May 29, 2024
From: HEALIOS K.K.
To: ABT HOLDING COMPANY; ATHERSYS, INC.; ADVANCED BIOTHERAPEUTICS, INC.; REGENESYS BVBA; REGENESYS, LLC
Reel/Frame 067566/0638 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT
Recorded Feb 1, 2024
From: ABT HOLDING COMPANY; ATHERSYS, INC.; ADVANCED BIOTHERAPEUTICS, INC.; REGENESYS BVBA; REGENESYS, LLC
To: HEALIOS K.K.
Reel/Frame 066435/0775 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 3, 2023
From: COX, CHARLES SAMUEL, JR.
To: THE BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
Reel/Frame 062264/0126 →
Continuity (4)
Continuation
PCTUS2011036235
· May 12, 2011
Provisional Application
61440617
· Feb 8, 2011
Provisional Application
61334001
· May 12, 2010
References Cited (338)
US 5486359A
· Caplan et al.
· 1996
[cited by applicant]
US 5827735A
· Young et al.
· 1998
[cited by applicant]
US 5906934A
· Grande et al.
· 1999
[cited by applicant]
US 6090625A
· Abuljadayel
· 2000
[cited by applicant]
US 6214369B1
· Grande et al.
· 2001
[cited by applicant]
US 6281012B1
· McIntosh
· 2001
[cited by applicant]
US 6328960B1
· McIntosh
· 2001
[cited by applicant]
US 6368636B1
· McIntosh
· 2002
[cited by applicant]
US 6387369B1
· Pittenger et al.
· 2002
[cited by applicant]
US 6653134B2
· Prockop et al.
· 2003
[cited by applicant]
US 6685936B2
· McIntosh
· 2004
[cited by applicant]
US 6777231B1
· Katz et al.
· 2004
[cited by applicant]
US 6797269B2
· Mosca
· 2004
[cited by applicant]
US 6875430B2
· McIntosh
· 2005
[cited by applicant]
US 7015037B1
· Furcht et al.
· 2006
[cited by examiner]
US 7045148B2
· Hariri
· 2006
[cited by applicant]
US 7056738B2
· Prockop et al.
· 2006
[cited by applicant]
US 7229827B2
· Kim et al.
· 2007
[cited by applicant]
US 7311905B2
· Hariri
· 2007
[cited by applicant]
US 7491388B1
· McIntosh
· 2009
[cited by applicant]
US 7659118B2
· Furcht et al.
· 2010
[cited by applicant]
US 7838289B2
· Furcht et al.
· 2010
[cited by applicant]
US 7883892B2
· Verfaillie et al.
· 2011
[cited by applicant]
US 7927587B2
· Blazer et al.
· 2011
[cited by applicant]
US 8075881B2
· Verfaillie et al.
· 2011
[cited by examiner]
US 8147824B2
· Maziarz et al.
· 2012
[cited by examiner]
US 8147826B2
· Fantuzzi
· 2012
[cited by examiner]
US 8192348B2
· Tranquillo et al.
· 2012
[cited by applicant]
US 8252280B1
· Furcht et al.
· 2012
[cited by applicant]
US 8268619B2
· Giacomello et al.
· 2012
[cited by applicant]
US 8409859B2
· Verfaillie et al.
· 2013
[cited by applicant]
US 8426200B2
· Verfaillie et al.
· 2013
[cited by applicant]
US 8580249B2
· Blazer et al.
· 2013
[cited by applicant]
US 8609406B2
· Subramanian et al.
· 2013
[cited by applicant]
US 8609412B2
· Panoskaltsis-Mortar et al.
· 2013
[cited by applicant]
US 9005964B2
· Verfaillie et al.
· 2015
[cited by applicant]
US 9057051B2
· Pauwelyn et al.
· 2015
[cited by applicant]
US 9090878B2
· Sancho-Bru et al.
· 2015
[cited by applicant]
US 9388388B2
· Verfaillie et al.
· 2016
[cited by applicant]
US 9447380B2
· Subramanian et al.
· 2016
[cited by applicant]
US 9526747B2
· Verfaillie et al.
· 2016
[cited by applicant]
US 9617513B2
· Young et al.
· 2017
[cited by applicant]
US 9644182B2
· Baksh et al.
· 2017
[cited by applicant]
US 9700601B2
· Blazer et al.
· 2017
[cited by applicant]
US 9764044B2
· Verfaillie et al.
· 2017
[cited by applicant]
US 9777258B2
· Sancho-Bru et al.
· 2017
[cited by applicant]
US 9789136B2
· Furcht et al.
· 2017
[cited by applicant]
US 9808485B2
· Maziarz et al.
· 2017
[cited by applicant]
US 9861660B2
· LaFrancesca et al.
· 2018
[cited by applicant]
US 9937208B2
· Mays et al.
· 2018
[cited by applicant]
US 9962407B2
· Deans et al.
· 2018
[cited by applicant]
US 9974809B2
· Furcht et al.
· 2018
[cited by applicant]
US 9974810B2
· Furcht et al.
· 2018
[cited by applicant]
US 9974811B2
· Furcht et al.
· 2018
[cited by applicant]
US 20010046489A1
· Habener et al.
· 2001
[cited by applicant]
US 20020061587A1
· Anversa
· 2002
[cited by applicant]
US 20030003090A1
· Prockop et al.
· 2003
[cited by applicant]
US 20030032179A1
· Hariri
· 2003
[cited by applicant]
US 20040033214A1
· Young et al.
· 2004
[cited by applicant]
US 20040213783A1
· Liversidge
· 2004
[cited by examiner]
US 20040235165A1
· Prockop et al.
· 2004
[cited by applicant]
US 20050053667A1
· Irvine
· 2005
[cited by examiner]
US 20050169896A1
· Li et al.
· 2005
[cited by applicant]
US 20050239897A1
· Pittenger
· 2005
[cited by applicant]
US 20050283844A1
· Furcht et al.
· 2005
[cited by applicant]
US 20060159666A1
· Willing et al.
· 2006
[cited by applicant]
US 20060177925A1
· Rosenberg et al.
· 2006
[cited by applicant]
US 20060228798A1
· Verfaillie et al.
· 2006
[cited by applicant]
US 20080095749A1
· Aggarwal
· 2008
[cited by applicant]
US 20080113434A1
· Davies et al.
· 2008
[cited by applicant]
US 20080194021A1
· Mays et al.
· 2008
[cited by applicant]
US 20080194024A1
· Mays
· 2008
[cited by applicant]
US 20080213227A1
· Aggarwal
· 2008
[cited by applicant]
US 20080311084A1
· Verfaillie et al.
· 2008
[cited by applicant]
US 20080317740A1
· Blazar et al.
· 2008
[cited by applicant]
US 20090004259A1
· Rabinovich
· 2009
[cited by examiner]
US 20090104159A1
· Prosper et al.
· 2009
[cited by applicant]
US 20090203128A1
· Giger
· 2009
[cited by applicant]
US 20100172885A1
· Pittenger
· 2010
[cited by applicant]
US 20100239542A1
· Young et al.
· 2010
[cited by applicant]
US 20100239543A1
· Young et al.
· 2010
[cited by applicant]
US 20100256233A1
· Kim
· 2010
[cited by examiner]
US 20110020292A1
· Van't Hof
· 2011
[cited by applicant]
US 20110020293A1
· Woda et al.
· 2011
[cited by applicant]
US 20110027238A1
· Aggarwal
· 2011
[cited by applicant]
US 20110111492A1
· Hu et al.
· 2011
[cited by applicant]
US 20110177595A1
· Furcht et al.
· 2011
[cited by applicant]
US 20110206647A1
· Woda et al.
· 2011
[cited by applicant]
US 20110212069A1
· Hamilton et al.
· 2011
[cited by applicant]
US 20110293578A1
· Busch et al.
· 2011
[cited by applicant]
US 20110305638A1
· Ting et al.
· 2011
[cited by examiner]
US 20110311496A1
· Pittenger
· 2011
[cited by applicant]
US 20110318313A1
· Cox et al.
· 2011
[cited by examiner]
US 20110318314A1
· Aggarwal
· 2011
[cited by applicant]
US 20110318315A1
· Aggarwal
· 2011
[cited by applicant]
US 20120009674A1
· Mays
· 2012
[cited by applicant]
US 20120021019A1
· Giacomello et al.
· 2012
[cited by applicant]
US 20120182103A1
· Miyabara
· 2012
[cited by applicant]
US 20120308531A1
· Pinxteren et al.
· 2012
[cited by applicant]
US 20130129686A1
· Highfill et al.
· 2013
[cited by applicant]
US 20140037596A1
· Woda et al.
· 2014
[cited by applicant]
US 20140134137A1
· Van't Hof
· 2014
[cited by applicant]
US 20140186307A1
· Busch et al.
· 2014
[cited by applicant]
US 20140234267A1
· Panoskaltsis-Mortar et al.
· 2014
[cited by applicant]
US 20140242629A1
· Woda et al.
· 2014
[cited by applicant]
US 20140295442A1
· Hamilton et al.
· 2014
[cited by applicant]
US 20140322135A1
· Roobrouck et al.
· 2014
[cited by applicant]
US 20150093364A1
· Busch et al.
· 2015
[cited by applicant]
US 20150118193A1
· Maziarz et al.
· 2015
[cited by applicant]
US 20160069903A1
· Lakadamyali
· 2016
[cited by examiner]
US 20160282336A1
· Hamilton et al.
· 2016
[cited by applicant]
US 20160326494A1
· Cunha et al.
· 2016
[cited by applicant]
US 20170022472A1
· Pinxteren et al.
· 2017
[cited by applicant]
US 20180110806A1
· Furcht et al.
· 2018
[cited by applicant]
US 20180311287A9
· Cox et al.
· 2018
[cited by applicant]
US 20190048314A1
· Woda et al.
· 2019
[cited by applicant]
US 20190233794A1
· Hu et al.
· 2019
[cited by applicant]
US 20190358258A1
· Deans et al.
· 2019
[cited by applicant]
US 20200246390A1
· Mays
· 2020
[cited by applicant]
US 20200390821A1
· Mays
· 2020
[cited by applicant]
US 20210205359A1
· Deans et al.
· 2021
[cited by applicant]
US 20210228626A1
· Deans et al.
· 2021
[cited by applicant]
US 20210299185A1
· Mays et al.
· 2021
[cited by applicant]
US 20220110982A1
· Mays et al.
· 2022
[cited by applicant]
US 20220118026A1
· Mays et al.
· 2022
[cited by applicant]
US 20220213435A1
· Hu et al.
· 2022
[cited by applicant]
EP 2539436A1
· 2013
[cited by applicant]
EP 2539439A1
· 2013
[cited by applicant]
WO WO9623870
· 1996
[cited by applicant]
WO WO9916863
· 1999
[cited by applicant]
WO WO9935243
· 1999
[cited by applicant]
WO WO0104268
· 2001
[cited by applicant]
WO 200111011A2
· 2001
[cited by applicant]
WO WO0108691
· 2001
[cited by applicant]
WO WO0121766
· 2001
[cited by applicant]
WO WO0121767
· 2001
[cited by applicant]
WO WO0208388
· 2001
[cited by applicant]
WO WO0162901
· 2001
[cited by applicant]
WO WO0234890
· 2002
[cited by applicant]
WO 2007087293A2
· 2007
[cited by applicant]
WO 2008020666A1
· 2008
[cited by applicant]
WO 2009007852A2
· 2009
[cited by applicant]
WO 2009092092A1
· 2009
[cited by applicant]
WO 2009136283A2
· 2009
[cited by applicant]
WO WO2011062584A1
· 2011
[cited by examiner]
WO 2011106476A1
· 2011
[cited by applicant]
Mebius RE and Kraal G. “Structure and function of the spleen.” Nature Reviews Immunology 5: 606-616. (Year: 2005).
[cited by examiner]
Jiang, Wenqi, et al., Cancer Biotherapy, Guangzhou Science & Technology Press, Chapter 6 Stem Cell Therapy, Section 2 Mesenchymal Stem Cells, Apr. 1, 2006, China (With English Translation Attached).
[cited by applicant]
Liu, Bin, Editor, Histology and Embryology, 1st Ed., Chap. 5(IV) Blood and Hemopoiesis, Peking University Medical Press, May 2005, China (With English Translation Attached).
[cited by applicant]
Pei, Xuetao, Editor, Stem Cell Biology, 1st Ed., 17.2.2 Mesenchymal Stem Cells (MSCs), Jul. 2003, China (With English Translation Attached).
[cited by applicant]
Li, Jing-Yuan et al., Telomerase Activity of Human Bone Marrow Mesenchymal Stem Cells, J. Zhejiang Univ. (Med Sci) 2004 Nov. 2004, 33(6):481-485, China.
[cited by applicant]
Liu et al., Telomerase Deficiency Impairs Differentiation of Mesenchymal Stem Cells, Exp. Cell Res., Mar. 10, 2004, vol. 294(1), pp. 1-8.
[cited by applicant]
Qi et al., “Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells” Nat. Acad. Sci. USA; 100:3305-3310 (2003).
[cited by applicant]
Moriscot et al., “Human bone marrow mesenchymal stem cell can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro” S…
[cited by applicant]
Morshead et al., “Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations” Nat. Med.; 8:268-73 (2002).
[cited by applicant]
Xiao et al., “Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury,” Stem Cells and Development; 14(6):722-733 (2005).
[cited by applicant]
Walker et al., “Progenitor cell therapies for traumatic brain injury; barriers and opportunities in translation” Disease Models & Mechanisms 2:(1-2):23-38, (31.02.2009).
[cited by applicant]
International Search Report for PCT/US 2011/36235; Aug. 9, 2011.
[cited by applicant]
Gendron, A, et al., ‘Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats,’ Brain Research, 2002, vol. 955, pp. 85-97.
[cited by applicant]
USPTO, Office Action and Form 892 issued in U.S. Appl. No. 13/150,491 on Apr. 13, 2017.
[cited by applicant]
USPTO, Office Action and Form 892 issued in U.S. Appl. No. 13/150,491 on Feb. 19, 2013.
[cited by applicant]
USPTO, Office Action and Form 892 issued in U.S. Appl. No. 13/150,491 on Aug. 7, 2012.
[cited by applicant]
Kim et al., Mesenchymal Stem Cell-Educated Macrophages: A Novel Type of Alternatively Activated Macrophages, Exp. Hematology, 2009, pp. 1445-1453, vol. 37.
[cited by applicant]
Yang et al., Experimental Study on Influence of Bone Marrow Mesenchymal Stem Cells on Activation and Function of Mouse Peritoneal Macrophages, Chinese J. of Hematology 2008 (English Translation by U.S. Patent Office).
[cited by applicant]
Riekstina et al., Embryonic Stem Cell Marker Expression Pattern in Human Mesenchymal Stem Cells Derived from Bone Marrow, Adipose Tissue, Heart and Dermis, Stem Cell Rev. and Rep., 2009, 5:378-386.
[cited by applicant]
Karaöz et al., A Comprehensive Characterization Study of Human Bone Marrow MSCs with an Emphasis on Molecular and Ultrastructural Properties, J. Cell. Physiol., 2011, pp. 1367-1382, vol. 226.
[cited by applicant]
Rosland et al., Long-Term Cultures of Bone Marrow-Derived Human Mesenchymal Stem Cells Frequently Undergo Spontaneous Malignant Transformation, Cancer Res., 2009, vol. 69(13), pp. 5331-5339.
[cited by applicant]
Greco et al., Functional Similarities Among Genes Regulated by Oct4 in Human Mesenchymal and Embryonic Stem Cells, Stem Cells, 2007, pp. 3143-3154, vol. 25.
[cited by applicant]
Wu et al., Generation of Pancreatic β Cells From Mesenchymal Stem Cells to Treat Type 1 Diabetes, OA Stem Cells, 2014; 2(1):5.
[cited by applicant]
Guo et al., Differentiation of Mesenchymal Stem Cells Into Dopaminergic Neuron-like Cells in Vitro, Biomedical and Environmental Sciences, 2005, 18:36-42.
[cited by applicant]
Piccinato et al., High OCT4 and Low p16INK4A Expressions Determine in Vitro Lifespan of Mesenchymal Stem Cells, Stem Cells International, 2015, vol. 2015, Article ID 369828, 11 pages.
[cited by applicant]
Yanjie et al., Effects of Notch-I Signalling Pathway on Differentiation of Marrow Mesenchymal Stem Cells Into Neurons in Vitro, NeuroRep., 2007, pp. 1443-1447, vol. 18(14).
[cited by applicant]
USPTO, Form 892, Notice of References Cited, Issued in U.S. Appl. No. 14/252,364, May 5, 2016.
[cited by applicant]
USPTO, Form 892, Notice of References Cited, Issued in U.S. Appl. No. 13/062,343, Apr. 11, 2018.
[cited by applicant]
USPTO, Form 892, Notice of References Cited, Issued in U.S. Appl. No. 14/252,364, Feb. 2, 2017.
[cited by applicant]
USPTO, Form 892, Notice of References Cited, Issued in U.S. Appl. No. 13/062,343, Apr. 27, 2017.
[cited by applicant]
USPTO, Form 892, Notice of References Cited, Issued in U.S. Appl. No. 14/266,480, Apr. 20, 2018.
[cited by applicant]
Decision on Motions, Patent Interference No. 105,953 SGL. Tech Center, Filed Sep. 26, 2014.
[cited by applicant]
USPTO, Form 892, Notice of References Cited, Issued in U.S. Appl. No. 13/150,481, Dec. 2, 2014.
[cited by applicant]
USPTO, Form 892, Notice of References Cited, Issued in U.S. Appl. No. 13/150,481, Sep. 10, 2015.
[cited by applicant]
Bicknese et al., Human Umbilical Cord Blood Cells can be Induced to Express Markers for Neurons and Glia, Cell Transplant., Apr. 2002, pp. 261-264, vol. 11(3).
[cited by applicant]
Goodwin et al., Multilineage Differentiation Activity by Cells Isolated From Umbilical Cord blood: Expression of Bone, Fat, and Neural Markers, Biol Blood Marrow Transplant., 2001, pp. 581-588, vol. 7(11).
[cited by applicant]
Weatherall, M., The Meaning and Importance of Drug Potency in Medicine, Clin. Pharmacol. Ther., Sep.-Oct. 1966, pp. 577-582, vol. 7(5).
[cited by applicant]
Wikipedia, “Potency” entry retrieved from https://en.wikipedia.org/wiki/Potency on Oct. 21, 2019.
[cited by applicant]
Ong, Shin-Yeu, et al., Hepatic Differentiation Potential of Commercially Available Human Mesenchymal Stem Cells, Tiss. Eng., 2006, pp. 3477-3485, vol. 12(12).
[cited by applicant]
USPTO, Office Action issued in U.S. Appl. No. 13/150,491 on Sep. 17, 2013.
[cited by applicant]
USPTO, Office Action and Form 892 from U.S. Appl. No. 13/301,186 issued Jan. 7, 2013.
[cited by applicant]
USPTO Notices of References Cited Forms 892 from U.S. Appl. No. 13/150,491, dated Nov. 7, 2012 and Jul. 31, 2013.
[cited by applicant]
Extended European Search Report for corresponding application No. EP11781272; Oct. 7, 2013.
[cited by applicant]
Experimental Hematology, 2009, v.37 pp. 1445-1453.
[cited by examiner]
Yang et al ( China J of Hematology, 2008).
[cited by examiner]
Office Action and Notice of References Cited (PTO form 892) from U.S. Appl. No. 13/301,186.
[cited by applicant]
Kolf, C.M., et al. Review Mesenchymal stromal cells: Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Research & Therapy, (2007) vol. 9:204 pp. 1-10.
[cited by applicant]
Notices of References Cited (PTO form 892) from U.S. Appl. No. 13/150,491, dated Nov. 7, 2012 and Jul. 31, 2013.
[cited by applicant]
Liedtke, S., et al. Oct4 expression revisited; potential pitfalls for data misinterpretation in stem cell research. Biol. Chem., (2008) vol. 389, pp. 845-850.
[cited by applicant]
Atlasi, Y., et al. Oct4 Spliced Variants are Differentially Expressed in Human Pluripotent and Nonpluripotent Cells. Stem Cells, (2008) vol. 26, pp. 3068-3074.
[cited by applicant]
Moriscot, C., et al. Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or micro-environmental manipulation in vit…
[cited by applicant]
Roche, S., et al. Oct-4, Rex-1, and Gata-4 expression in human MSC increase the differentiation efficiency but not hTERT expression. J. Cell, Biochem. (2007) vol. 101, pp. 271-280.
[cited by applicant]
Tai, M.H., et al. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis (2005) vol. 26, pp. 495-502.
[cited by applicant]
Tondreau, T., et al. Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells (2005) vol. 23, pp. 1105-1112.
[cited by applicant]
Takeda, J., et al. Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Research (1992) vol. 20, No. 17, pp. …
[cited by applicant]
Brehm, A., et al. The Carboxy-Terminal Transactivation Domain of Oct-4 Acquires Cell Specificity through the POU Domain. Mol. Cell. Biol. (1997) vol. 17, No. 1, pp. 154-162.
[cited by applicant]
Jiang, Y., et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature (2002) vol. 418, pp. 41-49.
[cited by applicant]
Mahmood, A., et al. Treatment of Traumatic Brain Injury in Adult Rats with Intravenous Administration of Human Bone Marrow Stromal Cells. Neurosurgery (2003) vol. 53, pp. 697-703.
[cited by applicant]
Woodbury, D., et al. Adult Rat and Human Bone Marrow Stromal Cells Differentiate Into Neurons. J of Neuroscience Research (2000), vol. 61, pp. 364-370.
[cited by applicant]
Digirolamo, C.M., et al. Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. British Journal …
[cited by applicant]
Ohtaki, H., et al. Stem/progenitor cells from bone marrow decrease neuronal death in global ischemia by modulation of inflammatory/immune responses. PNAS (2008) vol. 105, No. 38, pp. 14638-14543.
[cited by applicant]
Cambrex specimens, “Poietics Human Mesenchymal Stem Cell Systems,” Cambrex BioScience Walkersville, Inc. (2005).
[cited by applicant]
Prockop, D., “Marrow stromal cells as stem cells for nonhematopoietic tissues” Science; 276:71-74 (1997).
[cited by applicant]
Bjornson et al., “Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo” Science; 283:534-537 (1999).
[cited by applicant]
Reyes et al., “Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells” Blood; 98:2615-25 (2001).
[cited by applicant]
Bouwens, L., “Transdifferentiation versus stem cell hypothesis for the regeneration of islet beta-cells in the pancreas” Microscopy Research and Technique; 43:332-336 (1998).
[cited by applicant]
Reyes et al., “Origin of endothelial progenitors in human postnatal bone marrow” J. Clin. Invest.; 109:1-10 (2002).
[cited by applicant]
Reyes et al., “Characterization of multilineage mesodermal progenitor cells in adult marrow” Abstract No. 124, American Society for Hematology (2001).
[cited by applicant]
Reyes et al., “Turning marrow into brain: generation of glial and neuronal cells from adult bone marrow mesenchymal stem cells” Abstract No. 1676, American Society for Hematology (2001).
[cited by applicant]
Reyes et al., “Skeletal smooth and cardiac muscle differentiation from single adult marrow derived mesodermal progenitor cells” Abstract No. 2610, American Society for Hematology (2001).
[cited by applicant]
Reyes et al., “In vitro and in vivo characterization of neural cells derived from mesenchymal stem cells” Abstract 2126, American Society for Hematology (2001).
[cited by applicant]
Reyes et al., “Endothelial cells generated from human marrow derived mesenchymal stem cells (MSC)” Abstract No. 2276, American Society for Hematology (2001).
[cited by applicant]
Zhao et al., “Immunohistochemical identification of multipotent adult progenitor cells from human bone marrow after transplantation into the rat brain” Brain Res Brain Res Protoc; 11:38-45 (2003).
[cited by applicant]
Jiang et al., “Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain” Exp. Hematol.; 30:896-904 (2002).
[cited by applicant]
Jiang et al., “Pluripotency of mesenchymal stem cells derived from adult marrow” Nature; 418:41-49 (2002).
[cited by applicant]
Schwartz, R., “Multipotent adult progenitor cells from bone marrow differentiate into hepatocyte-like cells” J Clin Invest.; 109:1291-1302 (2002).
[cited by applicant]
Zhao et al., “Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats” Exp Neurol; 174:11-20 (2002).
[cited by applicant]
Lamming et al., “Spontaneous circulation of myeloid-lymphoid-initiating cells and SCID-repopulating cells in sickle cell crisis” J. Clin. Invest.; 111:811-819 (2003).
[cited by applicant]
Qi al., “Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells” Nat. Acad. Sci. USA; 100:3305-3310 (2003).
[cited by applicant]
Verfaillie, C. “Investigator Profile” Journal of Hematotherapy and Stem Cell Research; 11:441-444 (2002).
[cited by applicant]
Verfaillie et al., “Stem cells: hype and reality” Hematology (Am Soc Hematol Educ Program); 369-391 (2002).
[cited by applicant]
Verfaille, C., “Optimizing hematopoietic stem cell engraftment: a novel role for thrombopoeitin” J. Clin. Invest.; 110:303-304 (2002).
[cited by applicant]
Liu et al., “Myeloid-lymphoid-initiating cells (ML-IC) are highly enriched in the rhodamine-C-Kit(+) CD33(−)CD38(−) fraction of umbilical cord CD34(+)” Exp. Hematol.; 30:582-589 (2002).
[cited by applicant]
Lewis et al., “Multi-lineage expansion potential of primitive hematopoietic progenitors: superiority of umbilical cord blood compared to mobilized peripheral blood” Exp. Hematol.; 28:1087-1095 (2002).
[cited by applicant]
Verfaillie, C.M., “Meeting Report on an NHLBI Workshop on ex vivo expansion of stem cells, Jul. 29, 1999, Washington D.C. National Heart Lung and Blood Institute” Exp. Hematol.; 28:361-364 (2000).
[cited by applicant]
Punzel et al., “The myeloid-lymphoid initiating cell (ML-IC) assay assesses the fate of multipotent human progenitors in vitro” Blood; 93:3750-3756 (1999).
[cited by applicant]
Roy et al “Expression and function of cell adhesion molecules on fetal liver, cord blood and bone marrow hematopoietic progenitors: implications for anatomical localization and developmental stage specific regulation of…
[cited by applicant]
Miller et al., “Ex vivo culture of CD34+/Lin−/DR-cells in stroma-derived soluble factors, interleukin-3, and macrophage inflammatory protein-1 alpha maintains not only myeloid but also lymphoid progenitors in a novel sw…
[cited by applicant]
Verfaillie, C., “Stem cells in chronic myelogenous Leukemia” Hematol. Oncol. Clin. North Am.; 11:1079-1114 (1997).
[cited by applicant]
Prosper et al., “Phenotypic and functional characterization of long-term culture-initiating cells present in peripheral blood progenitor collections of normal donors treated with granulocyte colony-stimulating factor” B…
[cited by applicant]
Lodie et al., “Systematic analysis of reportedly distinct populations of multipotent bone marrow-derived stem cells reveals a lack of distinction” Tissue Engineering; 8:739-751 (2002).
[cited by applicant]
Pagen Westphal, S., “Adult bone marrow eyed as source of stem cells” Boston Globe, Jan. 24, 2002.
[cited by applicant]
Pagen Westphal, S., “Ultimate stem cell discovered” New Scientist, Jan. 23, 2002.
[cited by applicant]
Wade et al., “Scientists herald a versatile adult cell” The New York Times on the Web, Jan. 25, 2002.
[cited by applicant]
Rosford et al., “The octamer motif present in the Rex-1 promoter binds Oct-1 and Oct-3 expressed by EC cells and ES cells” Biochem. Biophys. Res. Comm.; 203:1795-1802 (1994).
[cited by applicant]
Rosner et al., “Oct-3 is a maternal factor required for the first mouse embryonic division” Cell; 64:1103-1110 (1991).
[cited by applicant]
Pittenger et al., “Multilineage potential of adult human mesenchymal stem cells”; Science; 284:143-147 (1999).
[cited by applicant]
Ben-Shushan et al., “Rex1, a gene encoding a transcription factor expressed in the early embryo, is regulated via Oct-¾ and Oct-6 binding to and octamer site and a novel protein, R ox-1, binding to an adjacent site” Mol…
[cited by applicant]
Reyes et al., “Characterization of multipotent adult progenitor cells, a subpopulation of mesenchymal stem cells” Annals of the New York Academy of Science; 938:231-235 (2001).
[cited by applicant]
Anjos-Afonso and Bonnet, “Nonhematopoietic/endothelial SSE-1+ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment” Blood; 109:1298-1306 (2007).
[cited by applicant]
Bertani et al., “Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray” J Cell Sci.; 118:3925-36 (2005).
[cited by applicant]
Bodnar et al., “Extension of life-span by introduction of telomerase into normal human cells” Science; 279:349-352 (1998).
[cited by applicant]
Horwitz et al., “Clarification of the nomenclature for MSC: the international society for cellular therapy position paper” Cytotherapy; 7:393-395 (2005).
[cited by applicant]
Lu et al., “Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact” J Neurosci Res; 77:174-91 (2004).
[cited by applicant]
Neuhuber et al., “Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype” J Neurosci Res; 77:…
[cited by applicant]
Simonsen et al., “Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells” Nature Biotechnology; 20:592-596 (2002).
[cited by applicant]
Zimmerman et al., “Lack of telomerase activity in human mesenchymal stem cells” Leukemia; 17:1146-1149 (2003).
[cited by applicant]
Izadpanah et al., “Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue” Journal of Cellular Biochemistry; 99:1285-1297 (2006).
[cited by applicant]
Long et al., “Neural cell differentiation in vitro from adult human bone marrow mesenchymal stem cells” Stem Cells and Development; 14:65-69 (2005).
[cited by applicant]
Moriscot et al., “Human bone marrow mesenchymal stem cell can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or macroenvironmental manipulation in vitro” S…
[cited by applicant]
Sanchez-Ramos et al., “Adult bone marrow stromal cells differentiate into neural cells in vitro” Exp. Neurol.; 164:247-56 (2000).
[cited by applicant]
Eglitis et al., “Hematopoietic cells differentiate into both microglia and macroglia in the brain of adult mice” Proc. Natl. Acad. Sci. USA; 94:4080-85 (1997).
[cited by applicant]
Kopen et al., “Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains” Proc. Natl. Acad. Sci. USA; 96:10711-16 (1999).
[cited by applicant]
Lagasse et al., “Purified hematopoietic stem cells can differentiate into hepatocytes in vivo” Nature Medicine; 6:1229-1234 (2000).
[cited by applicant]
Wang, X. et al., “Cell fusion is the principal source of bone-marrow-derived hepatocytes” Nature; 422:897-901 (2003).
[cited by applicant]
Giles, J., “The trouble with replication” Nature, 422:344-347 (2006).
[cited by applicant]
Verfaillie, C.M., Multipotent adult progenitor cells: an update: Novartis Found Symp., 254:55-65 (2005).
[cited by applicant]
Aldhous et al., “Fresh questions on stem cell findings” New Scientist, Mar. 21, 2007.
[cited by applicant]
Brazelton et al., “From marrow to brain: expression of neuronal phenotypes in adult mice” Science; 290:1775-9 (2000).
[cited by applicant]
Clarke et al., “Generalized potential of adult neural stem cells” Science; 288: 1660-3 (2000).
[cited by applicant]
Johansson et al., “Neural stem cells in the adult human brain” Exp. Cell. Res.; 253:733-6 (1999).
[cited by applicant]
Mezey et al., “Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow” Science; 290:1779-82 (2000).
[cited by applicant]
Morshead et al., “Hematopoletic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations” Nat. Med.; 8:268-73 (2002).
[cited by applicant]
Petersen et al., “Bone marrow as a potential source of hepatic oval cells” Science; 284:1168-70 (1999).
[cited by applicant]
Scintu et al., “Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments” BMC Neurosci.; 7:14 (2006).
[cited by applicant]
U.S. Patent and Trademark Office, Office Action dated Jun. 24, 2005 in related U.S. Appl. No. 10/040,757.
[cited by applicant]
U.S. Patent and Trademark Office, Office Action and 892 dated Jun. 27, 2008 in related U.S. Appl. No. 10/467,963.
[cited by applicant]
U.S. Patent and Trademark Office, Office Action dated Oct. 15, 2009 in related U.S. Appl. No. 10/467,963.
[cited by applicant]
U.S. Patent and Trademark Office, Office Action and 892 dated Apr. 7, 2008 in related U.S. Appl. No. 11/151,689.
[cited by applicant]
U.S. Patent and Trademark Office, Office Action dated Jan. 4, 2006 in related U.S. Appl. No. 11/238,234.
[cited by applicant]
U.S. Patent and Trademark Office, Office Action dated Aug. 29, 2006 in related U.S. Appl. No. 11/238,234.
[cited by applicant]
Vendrame et al., “Cord blood rescues stroke-induced changes in splenocyte phenotype and function” Experimental Neurology; 199(1):191-200 (2006).
[cited by applicant]
Xioa et al., “Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury,” Stem Cells and Development; 14(6):722-733 (2005).
[cited by applicant]
Walker et al., “Progenitor cell therapies for traumatic brain injury; barriers and opportunities in translation” Disease Models & Mechanisms 2:(1-2):23-38, (Feb. 31, 2009).
[cited by applicant]
U.S. Patent and Trademark Office, Office Action and 892 dated Apr. 3, 2007 in related U.S. Appl. No. 11/238,234.
[cited by applicant]
U.S. Patent and Trademark Office, Office Action dated Oct. 7, 2008 in related U.S. Appl. No. 11/238,234.
[cited by applicant]
Communication and 1449, filed Oct. 2, 2007 in related U.S. Appl. No. 11/238,234, and supplemental 1449 submitted on Oct. 4, 2007.
[cited by applicant]
Information Disclosure Statement, Second Communication and PTO/SB/08b, filed Dec. 24, 2008 in related U.S. Appl. No. 11/238,234.
[cited by applicant]
International Search Report for PCT/US2011/36235; dated Aug. 9, 2011.
[cited by applicant]
Mays, R.W., et al. Development of adult pluripotent stem cell therapies for ischemic injury and disease. Expert Opinion on Biological Therapy; ( 2007) vol. 7, No. 2; pp. 173-184.
[cited by applicant]
Walker, P.A., et al. Intravenous multipotent adult progenitor cell therapy for traumatic brain injury: Preserving the blood brain barrier via an interaction with splenocytes. Exp Neurology; (2010) vol. 225, No. 2; pp. 3…
[cited by applicant]
Walker, P.A., et al. Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population. J Neuroinflammation; (2012) vol. 9, No. 1; pp. 228-241.
[cited by applicant]
Extended European Search Report for corresponding application No. EP11781272; dated Oct. 7, 2013.
[cited by applicant]
Gendron, A, et al., ‘Temporal affects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats,’ Brain Research, 2002, vol. 955, pp. 85-97.
[cited by applicant]
Benner, E.J. et al., ‘Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease,’ Proc Natl Acad Sci USA, 2004, vol. 101, pp. 9435-9440.
[cited by applicant]
Boozer et al., “Global Characterization and Genomic Stability of Human MultiStem, A Multipotent Adult Progenitor Cell,” J Stem Cells., 4(1), pp. 17-28, 2009.
[cited by applicant]
U.S. Appl. No. 11/808,933, filed Jun. 13, 2007, High Oct¾ MAPCs and Methods Therefor.
[cited by applicant]
U.S. Appl. No. 13/510,491, filed May 17, 2012, Reducing Inflammation Using Cell Therapy.
[cited by applicant]
U.S. Appl. No. 13/071,801, filed Mar. 25, 2011, Modulation of Macrophahe Activation.
[cited by applicant]