Granted Patent
B2
US 12,653,840 · App. 17/752,505 · Granted Jun 16, 2026
Methods for production of platelets from pluripotent stem cells and compositions thereof
A61K35/19C12N5/0644C12N2501/04C12N2501/20C12N2501/2306C12N2501/2309C12N2501/2311C12N2501/30C12N2501/40C12N2501/727C12N2501/734C12N2501/91C12N2506/11Y02A50/30
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Abstract
Methods for production of platelets from pluripotent stem cells, such as human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are provided. These methods may be performed without forming embryoid bodies or clusters of pluripotent stem cells, and may be performed without the use of stromal inducer cells. Additionally, the yield and/or purity can be greater than has been reported for prior methods of producing platelets from pluripotent stem cells. Also provided are compositions and pharmaceutical preparations comprising platelets, preferably produced from pluripotent stem cells.
Claims (21)
1 . A cryopreserved composition comprising platelets produced by a method comprising subjecting megakaryocytes in a feeder free culture conditions to shear forces to cause the formation in culture of pro-platelets that release platelets, at least 60% of which are positive for CD41a expression, wherein:
the platelets have a shelf-life of at least 8 to 15 days when stored at 22-24° C. and maintain viability for use in a human patient.
2 . The cryopreserved composition of claim 1 , wherein at least 60% of the platelets of the composition are positive for CD41a and CD42b expression.
3 . The cryopreserved composition of claim 1 , wherein the megakaryocytes are subjected to shear forces of 1-4.5 dynes/cm 2 .
4 . The cryopreserved composition of claim 1 , wherein the feeder free culture conditions comprise culturing the megakaryocytes on a microfluidic chip and flowing media past the megakaryocytes.
5 . The cryopreserved composition of claim 4 , wherein the media is flowed past the megakaryocytes at a rate of 5-25 microliters/min.
6 . The cryopreserved composition of claim 1 , wherein the feeder free culture conditions comprise a protease inhibitor.
7 . The cryopreserved composition of claim 6 , wherein the protease inhibitor is added to the feeder free conditions at a time of peak production of platelets.
8 . The cryopreserved composition of claim 6 , wherein the protease inhibitor an MMP inhibitor.
9 . The cryopreserved composition of claim 6 , wherein the protease inhibitor is an MMP8 specific inhibitor, optional wherein the feeder free culture conditions comprise an MMP8 specific inhibitor and an MMP general inhibitor.
10 . The cryopreserved composition of claim 9 , wherein the MMP8 specific inhibitor is MMP8-I ((3R)-(+)-[2-(4-Methoxybenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-hydroxamate]).
11 . The cryopreserved composition of claim 1 , wherein the feeder free culture conditions comprise thrombopoietin (TPO) or a TPO agonist.
12 . The cryopreserved composition of claim 11 , wherein the feeder free culture conditions further comprise: Stem Cell Factor (SCF), Interleukin (IL)-6, and IL-9; or SCF and IL-11.
13 . The cryopreserved composition of claim 12 , wherein the feeder free conditions comprise TPO at 10-100 ng/ml, SCF at 0.5-100 ng/ml, and:
IL-11 at 10-100 ng/ml and optionally at least one ROCK inhibitor and/or Heparin at 2.5-25 Units/ml; or
IL-6 at 5-25 ng/ml, IL-9 at 5-25 ng/ml, and optionally at least one ROCK inhibitor and/or Heparin at 2.5-25 units/ml.
14 . The cryopreserved composition of claim 1 , comprising at least 10{circumflex over ( )}8 human platelets, wherein at least 60% of the human platelets are positive for CD41a and CD42b expression.
15 . The cryopreserved composition of claim 1 , comprising: at least 10{circumflex over ( )}8 human platelets, wherein at least 60% of the platelets are positive for CD41a and CD42b expression; and an agent that reduces platelet clearance, blocks platelet phagocytosis, increases platelet circulation time, and/or increases platelet storage time.
16 . The cryopreserved composition of claim 1 , wherein the platelets have a shelf-life of at least 10 days when stored at 22-24° C.
17 . The cryopreserved composition of claim 15 , wherein the composition comprises an agent that reduces platelet clearance or increases platelet circulation time.
18 . The cryopreserved composition of claim 15 , wherein the composition comprises an agent that blocks platelet phagocytosis.
Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY'S DATA PREVIOUSLY RECORDED AT REEL: 062539 FRAME: 0263. ASSIGNOR(S) HEREBY CONFIRMS THE CHANGE OF NAME .
Recorded Feb 13, 2023
From: OCATA THERAPEUTICS, INC.
To: ASTELLAS INSTITUTE FOR REGENERATIVE MEDICINE
Reel/Frame 063117/0758 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 27, 2023
From: FENG, QIANG; LU, SHI-JIANG; LANZA, ROBERT P.
To: ADVANCED CELL TECHNOLOGY, INC.
Reel/Frame 062510/0923 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 27, 2023
From: FENG, QIANG; LU, SHI-JIANG; LANZA, ROBERT P.
To: ADVANCED CELL TECHNOLOGY, INC.
Reel/Frame 062512/0388 →
CHANGE OF NAME
Recorded Jan 27, 2023
From: ADVANCED CELL TECHNOLOGY, INC.
To: OCATA THERAPEUTICS, INC.
Reel/Frame 062539/0260 →
CHANGE OF NAME
Recorded Jan 27, 2023
From: OCATA THERAPEUTICS, INC.
To: ASTELLAS INSITUTE FOR REGENERATIVE MEDICINE
Reel/Frame 062539/0263 →
Continuity (5)
Continuation
14653969
Provisional Application
61787476
· Mar 15, 2013
Provisional Application
61740699
· Dec 21, 2012
References Cited (400)
US 5128259A
· Morgan
· 1992
[cited by applicant]
US 5599705A
· Cameron
· 1997
[cited by applicant]
US 5635387A
· Fei et al.
· 1997
[cited by applicant]
US 5649903A
· Deniega
· 1997
[cited by applicant]
US 5914268A
· Keller et al.
· 1999
[cited by applicant]
US 6429012B1
· Kraus et al.
· 2002
[cited by applicant]
US 6479286B1
· Nelson et al.
· 2002
[cited by applicant]
US 6602711B1
· Thomson et al.
· 2003
[cited by applicant]
US 7220584B2
· Thomson et al.
· 2007
[cited by applicant]
US 7282201B2
· Miura et al.
· 2007
[cited by applicant]
US 7374934B2
· Keller et al.
· 2008
[cited by applicant]
US 7455983B2
· Xu et al.
· 2008
[cited by applicant]
US 7476326B2
· Ahn et al.
· 2009
[cited by applicant]
US 7718420B2
· Kim et al.
· 2010
[cited by applicant]
US 7790458B2
· Xu et al.
· 2010
[cited by applicant]
US 8017393B2
· Lanza et al.
· 2011
[cited by applicant]
US 8252587B2
· Fong et al.
· 2012
[cited by applicant]
US 8263403B2
· Perry et al.
· 2012
[cited by applicant]
US 8372642B2
· Rajesh et al.
· 2013
[cited by applicant]
US 8535943B2
· Nakano et al.
· 2013
[cited by applicant]
US 8546141B2
· Nakauchi et al.
· 2013
[cited by applicant]
US 8822218B2
· Kimbrel et al.
· 2014
[cited by applicant]
US 8933071B2
· Crispino et al.
· 2015
[cited by applicant]
US 8962321B2
· Kimbrel et al.
· 2015
[cited by applicant]
US 9012221B2
· Baruch et al.
· 2015
[cited by applicant]
US 9074186B2
· Murphy et al.
· 2015
[cited by applicant]
US 9109202B2
· Spanholtz
· 2015
[cited by applicant]
US 9121008B2
· Tsai
· 2015
[cited by applicant]
US 9200254B2
· Eto et al.
· 2015
[cited by applicant]
US 9410123B2
· Lanza et al.
· 2016
[cited by applicant]
US 9655925B2
· Lowdell et al.
· 2017
[cited by applicant]
US 9763984B2
· Feng et al.
· 2017
[cited by applicant]
US 9938500B2
· Lanza et al.
· 2018
[cited by applicant]
US 9988602B2
· Lanza et al.
· 2018
[cited by applicant]
US 9988603B2
· Li et al.
· 2018
[cited by applicant]
US 9993503B2
· Feng et al.
· 2018
[cited by applicant]
US 20020035735A1
· Schatten et al.
· 2002
[cited by applicant]
US 20030153082A1
· Bhatia
· 2003
[cited by applicant]
US 20030166273A1
· Kaufman et al.
· 2003
[cited by applicant]
US 20030175954A1
· Shamblott et al.
· 2003
[cited by applicant]
US 20040013676A1
· Bae et al.
· 2004
[cited by applicant]
US 20040052771A1
· Lim
· 2004
[cited by applicant]
US 20040105860A1
· Losordo
· 2004
[cited by applicant]
US 20040136973A1
· Huberman et al.
· 2004
[cited by applicant]
US 20040229350A1
· Strelchenko et al.
· 2004
[cited by applicant]
US 20050032210A1
· Sato et al.
· 2005
[cited by applicant]
US 20050042751A1
· Goldman et al.
· 2005
[cited by applicant]
US 20050153443A1
· Lanza et al.
· 2005
[cited by applicant]
US 20050176142A1
· Nakorn et al.
· 2005
[cited by applicant]
US 20050221482A1
· Burt et al.
· 2005
[cited by applicant]
US 20050221487A1
· Zon et al.
· 2005
[cited by applicant]
US 20060099198A1
· Thomson et al.
· 2006
[cited by applicant]
US 20070042344A1
· Choi et al.
· 2007
[cited by applicant]
US 20070077654A1
· Thomson
· 2007
[cited by applicant]
US 20070141703A1
· Stanley et al.
· 2007
[cited by applicant]
US 20070218552A1
· Giarratana et al.
· 2007
[cited by applicant]
US 20070243608A1
· Kyba et al.
· 2007
[cited by applicant]
US 20070298496A1
· Kuo et al.
· 2007
[cited by applicant]
US 20080003674A1
· Slukvin et al.
· 2008
[cited by applicant]
US 20080014180A1
· Lanza et al.
· 2008
[cited by applicant]
US 20080014183A1
· Okano et al.
· 2008
[cited by applicant]
US 20080057041A1
· Chung et al.
· 2008
[cited by applicant]
US 20080108044A1
· Rajesh et al.
· 2008
[cited by applicant]
US 20080160564A1
· Rich
· 2008
[cited by applicant]
US 20080166327A1
· Asahara et al.
· 2008
[cited by applicant]
US 20080166751A1
· Asahara et al.
· 2008
[cited by applicant]
US 20090246875A1
· Yamanaka et al.
· 2009
[cited by applicant]
US 20090304646A1
· Sakurada et al.
· 2009
[cited by applicant]
US 20100216181A1
· Daigh et al.
· 2010
[cited by applicant]
US 20100248361A1
· Lasky et al.
· 2010
[cited by applicant]
US 20100316613A1
· Upton et al.
· 2010
[cited by applicant]
US 20110053267A1
· Nakauchi et al.
· 2011
[cited by applicant]
US 20110064705A1
· Lanza et al.
· 2011
[cited by applicant]
US 20110086424A1
· Lanza et al.
· 2011
[cited by applicant]
US 20110151554A1
· Yuo et al.
· 2011
[cited by applicant]
US 20110280861A1
· Scadden et al.
· 2011
[cited by applicant]
US 20110305675A1
· Scadden et al.
· 2011
[cited by applicant]
US 20120009618A1
· Yu et al.
· 2012
[cited by applicant]
US 20120027731A1
· Lanza et al.
· 2012
[cited by applicant]
US 20120238020A1
· Mitchell et al.
· 2012
[cited by applicant]
US 20120238023A1
· Eto et al.
· 2012
[cited by applicant]
US 20120276063A1
· Meyer et al.
· 2012
[cited by applicant]
US 20120282228A1
· Bhasin
· 2012
[cited by applicant]
US 20120315338A1
· Li et al.
· 2012
[cited by applicant]
US 20130011924A1
· Niwa et al.
· 2013
[cited by applicant]
US 20130210141A1
· Rajesh et al.
· 2013
[cited by applicant]
US 20140037600A1
· Yu et al.
· 2014
[cited by applicant]
US 20140045265A1
· Belmonte et al.
· 2014
[cited by applicant]
US 20140086883A1
· Poncz et al.
· 2014
[cited by applicant]
US 20140127815A1
· Eto et al.
· 2014
[cited by applicant]
US 20140142102A1
· Fairfax et al.
· 2014
[cited by applicant]
US 20140205582A1
· Karsunky et al.
· 2014
[cited by applicant]
US 20140227780A1
· Nishino et al.
· 2014
[cited by applicant]
US 20140271590A1
· Feng et al.
· 2014
[cited by applicant]
US 20140315760A1
· Ratner et al.
· 2014
[cited by applicant]
US 20150079030A1
· Moore
· 2015
[cited by applicant]
US 20150087065A1
· Haecker
· 2015
[cited by applicant]
US 20150140657A1
· Kimbrel et al.
· 2015
[cited by applicant]
US 20150203819A1
· Murphy et al.
· 2015
[cited by applicant]
US 20150361398A1
· Sandler et al.
· 2015
[cited by applicant]
US 20160002586A1
· Mitchell
· 2016
[cited by applicant]
US 20160002599A1
· Eto
· 2016
[cited by applicant]
US 20160011545A1
· Kakishima et al.
· 2016
[cited by applicant]
US 20160022736A1
· Feng et al.
· 2016
[cited by applicant]
US 20160145573A1
· Liu
· 2016
[cited by applicant]
US 20160168540A1
· Hirata et al.
· 2016
[cited by applicant]
US 20160177265A1
· Matsubara et al.
· 2016
[cited by applicant]
US 20160206783A1
· Dietz et al.
· 2016
[cited by applicant]
US 20160235889A1
· Pallotta et al.
· 2016
[cited by applicant]
US 20160272941A1
· Baruch et al.
· 2016
[cited by applicant]
US 20170121681A1
· Lanza et al.
· 2017
[cited by applicant]
US 20170152481A1
· Lanza et al.
· 2017
[cited by applicant]
US 20190002828A1
· Lanza et al.
· 2019
[cited by applicant]
US 20190002829A1
· Li et al.
· 2019
[cited by applicant]
US 20200131475A1
· Kimbrel et al.
· 2020
[cited by applicant]
US 20200157503A1
· Lanza et al.
· 2020
[cited by applicant]
US 20200263132A1
· Lanza et al.
· 2020
[cited by applicant]
US 20250090586A1
· Feng et al.
· 2025
[cited by applicant]
US 20250099505A1
· Feng et al.
· 2025
[cited by applicant]
AU 2009244231A1
· 2009
[cited by applicant]
AU 2009244236A1
· 2009
[cited by applicant]
AU 2013201444A1
· 2013
[cited by applicant]
CN 1141061A
· 1997
[cited by applicant]
CN 1204369A
· 1999
[cited by applicant]
CN 1499980A
· 2004
[cited by applicant]
CN 1556197A
· 2004
[cited by applicant]
CN 1564864A
· 2005
[cited by applicant]
CN 1192796C
· 2005
[cited by applicant]
CN 1778929A
· 2006
[cited by applicant]
CN 101045914A
· 2007
[cited by applicant]
CN 101045915A
· 2007
[cited by applicant]
CN 101052710A
· 2007
[cited by applicant]
CN 101063110A
· 2007
[cited by applicant]
CN 101160391A
· 2008
[cited by applicant]
CN 101310007A
· 2008
[cited by applicant]
CN 101500609A
· 2009
[cited by applicant]
CN 101501185A
· 2009
[cited by applicant]
CN 101528915A
· 2009
[cited by applicant]
CN 101530427A
· 2009
[cited by applicant]
CN 101649305A
· 2010
[cited by applicant]
CN 101678079A
· 2010
[cited by applicant]
CN 101981181A
· 2011
[cited by applicant]
CN 102068686A
· 2011
[cited by applicant]
CN 102083960A
· 2011
[cited by applicant]
CN 102083963A
· 2011
[cited by applicant]
CN 102256999A
· 2011
[cited by applicant]
CN 102388130A
· 2012
[cited by applicant]
CN 102660495A
· 2012
[cited by applicant]
CN 102732483A
· 2012
[cited by applicant]
CN 102822332A
· 2012
[cited by applicant]
CN ZL200980125862A
· 2014
[cited by applicant]
CN 104328087A
· 2015
[cited by applicant]
CN 104946591A
· 2015
[cited by applicant]
CN 106434527A
· 2017
[cited by applicant]
CN 107208062A
· 2017
[cited by applicant]
CN 107429230A
· 2017
[cited by applicant]
CN 111542597A
· 2020
[cited by applicant]
CN 112280739A
· 2021
[cited by applicant]
EP 1352060A2
· 2003
[cited by applicant]
EP 2013331A2
· 2009
[cited by applicant]
EP 2288690A2
· 2011
[cited by applicant]
EP 2291513A2
· 2011
[cited by applicant]
EP 2377923A1
· 2011
[cited by applicant]
EP 2377924A1
· 2011
[cited by applicant]
EP 2377925A1
· 2011
[cited by applicant]
EP 2426197A1
· 2012
[cited by applicant]
EP 2507359A1
· 2012
[cited by applicant]
EP 2507365A1
· 2012
[cited by applicant]
EP 2712921A1
· 2014
[cited by applicant]
JP 2002515756A
· 2002
[cited by applicant]
JP 2003533698A
· 2003
[cited by applicant]
JP 2004504834A
· 2004
[cited by applicant]
JP 2004531262A
· 2004
[cited by applicant]
JP 2004535389A
· 2004
[cited by applicant]
JP 2005511084A
· 2005
[cited by applicant]
JP 2007089432A
· 2007
[cited by applicant]
JP 2009533059A
· 2009
[cited by applicant]
JP 2011519576A
· 2011
[cited by applicant]
JP 2011519577A
· 2011
[cited by applicant]
JP 2012518415A
· 2012
[cited by applicant]
JP 2012519005A
· 2012
[cited by applicant]
JP 2013512673A
· 2013
[cited by applicant]
JP 2013512676A
· 2013
[cited by applicant]
JP 2013126423A
· 2013
[cited by applicant]
JP 5630781B2
· 2014
[cited by applicant]
JP 2015057070A
· 2015
[cited by applicant]
JP 2015061539A
· 2015
[cited by applicant]
JP 5748654B2
· 2015
[cited by applicant]
JP 2016063838A
· 2016
[cited by applicant]
NZ 518191A
· 2004
[cited by applicant]
NZ 572842A
· 2012
[cited by applicant]
WO WO9517500A1
· 1995
[cited by applicant]
WO WO9833891A1
· 1998
[cited by applicant]
WO WO9967360A2
· 1999
[cited by applicant]
WO WO0011139A1
· 2000
[cited by applicant]
WO WO0136589A2
· 2001
[cited by applicant]
WO WO0188539A1
· 2001
[cited by applicant]
WO WO2002010347A2
· 2002
[cited by applicant]
WO WO02089730A2
· 2002
[cited by applicant]
WO WO2002092756A2
· 2002
[cited by applicant]
WO WO03046141A2
· 2003
[cited by applicant]
WO WO03050251A2
· 2003
[cited by applicant]
WO WO2004007698A1
· 2004
[cited by applicant]
WO WO2004029231A1
· 2004
[cited by applicant]
WO WO2004044146A2
· 2004
[cited by applicant]
WO WO2005040391A1
· 2005
[cited by applicant]
WO WO2005049812A1
· 2005
[cited by applicant]
WO WO2005078073A2
· 2005
[cited by applicant]
WO WO2005118780A1
· 2005
[cited by applicant]
WO WO2006001954A2
· 2006
[cited by applicant]
WO WO2006050330A2
· 2006
[cited by applicant]
WO WO2006090882A1
· 2006
[cited by applicant]
WO WO2006118350A1
· 2006
[cited by applicant]
WO WO2006130651A2
· 2006
[cited by applicant]
WO WO2007005595A1
· 2007
[cited by applicant]
WO WO2007032634A1
· 2007
[cited by applicant]
WO WO2007037682A1
· 2007
[cited by applicant]
WO WO2007095064A2
· 2007
[cited by applicant]
WO WO2007120811A2
· 2007
[cited by applicant]
WO WO2008151386A1
· 2008
[cited by applicant]
WO WO2008151390A1
· 2008
[cited by applicant]
WO WO2009045360A2
· 2009
[cited by applicant]
WO WO2009052389A1
· 2009
[cited by applicant]
WO WO2009104825A1
· 2009
[cited by applicant]
WO WO2009119105A1
· 2009
[cited by applicant]
WO WO2009120891A2
· 2009
[cited by applicant]
WO WO2009122747A1
· 2009
[cited by applicant]
WO WO2009137624A2
· 2009
[cited by applicant]
WO WO2009137629A2
· 2009
[cited by applicant]
WO WO2010025506A1
· 2010
[cited by applicant]
WO WO2010096746A1
· 2010
[cited by applicant]
WO WO2010099539A1
· 2010
[cited by applicant]
WO WO2011034073A1
· 2011
[cited by applicant]
WO WO2011068896A1
· 2011
[cited by applicant]
WO WO2011069127A1
· 2011
[cited by applicant]
WO WO2012036257A1
· 2012
[cited by applicant]
WO WO2012145384A1
· 2012
[cited by applicant]
WO WO2012157586A1
· 2012
[cited by applicant]
WO WO2012158983A2
· 2012
[cited by applicant]
WO WO2014138485A1
· 2014
[cited by applicant]
WO WO2015179301A1
· 2015
[cited by applicant]
WO WO2015191632A1
· 2015
[cited by applicant]
WO WO2016160860A1
· 2016
[cited by applicant]
WO WO2020163269A1
· 2020
[cited by applicant]
Valeri et al. (2005, Transfusion, vol. 45, pp. 1890-1898) (Year: 2005).
[cited by examiner]
Lu et al. (2011, Cell Research, vol. 21, pp. 530-545) (Year: 2011).
[cited by examiner]
Johnson et al. (2020, Transfusion, vol. 60, pp. 2969-2981). (Year: 2020).
[cited by examiner]
U.S. Dept. Health and Human Services U.S. Dept. Health and Human Services (2023, Alternative Procedures for the Manufacture of Cold-Stored Platelets Intended for the Treatment of Active Bleeding when Conventional Platel…
[cited by examiner]
Valeri et al. (2004, J. Trauma, vol. 57, pgs. S22-S25). (Year: 2004).
[cited by examiner]
Gordon-Keylock et al., Endothelio-hematopoietic relationship: getting closer to the beginnings. BMC Biol. Dec. 28, 2011;9:88. doi: 10.1186/1741-7007-9-88.
[cited by applicant]
Huang et al., Histology of Rhesus Monkey. Guangdong Science and Technology Press. 1st edition. Jun. 2010. PP. 54-57.
[cited by applicant]
Kim et al., Human peripheral blood-derived CD31+ cells have robust angiogenic and vasculogenic properties and are effective for treating ischemic vascular disease. J Am Coll Cardiol. Aug. 10, 2010;56(7):593-607. doi: 10…
[cited by applicant]
Liu et al., Hypoxia Enhances the Differentiation of Hemogenic Endothelial Cells from Human Embryonic Stem Cells through Up-regulating Wnt5a Signal. Scientia Sinica Vitae. Oct. 2013; 43(10): 877-885. DOI:10.1360/052013-2…
[cited by applicant]
Monzen et al., Terminal maturation of megakaryocytes and platelet production by hematopoietic stem cells irradiated with heavy-ion beams. Radiat Res. Jul. 2011;176(1):8-16. doi: 10.1667/rr2392.1. Epub Apr. 29, 2011.
[cited by applicant]
Nieswandt et al., Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. Mar. 15, 1999;59(6):1295-300.
[cited by applicant]
Rolfes et al., Platelets Fuel the Inflammasome Activation of Innate Immune Cells. Cell Rep. May 12, 2020;31(6):107615. doi: 10.1016/j.celrep.2020.107615.
[cited by applicant]
Salvagiotto et al., A Defined, Feeder-Free, Serum-Free System to Generate In Vitro Hematopoietic Progenitors and Differentiated Blood Cells from hESCs and hiPSCs. PLoS One. Mar. 18, 2011;6(3):e17829. doi: 10.1371/journa…
[cited by applicant]
Van Der Heyde et al., Platelet depletion by anti-CD41 (alphaIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines.…
[cited by applicant]
Xin et al., In vitro induction of cord blood CD34+cells differentiation into mature megakaryocytes and production of platelets Chinese Journal of Tissue Engineering Research. Mar. 2009; 13(10): 1976-1980.
[cited by applicant]
International Search Report and Written Opinion mailed Apr. 30, 2014 for Application No. PCT/US2013/077334.
[cited by applicant]
International Preliminary Report on Patentability mailed Jul. 2, 2015 for Application No. PCT/US2013/077334.
[cited by applicant]
Extended European Search Report mailed Aug. 3, 2016 in connection with European Application No. 13865661.6.
[cited by applicant]
Extended European Search Report mailed Mar. 1, 2022 in connection with European Application No. 21196318.6.
[cited by applicant]
[No Author Listed], CBC (Complete Blood Count). University of Iowa Diagnostic Laboratories. Retrieved on Jul. 2, 2020. 2 pages. Accessible at https://www.healthcare.uiowa.edu/path_handbook/rhandbook/test299.html.
[cited by applicant]
[No Author Listed], Correction for Wani et al., Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant β 2-microglobulin gene. Proc Natl Acad Sci U S A. Jul. 5, 2…
[cited by applicant]
[No Author Listed], Life technologies, Guidelines for Maintaining Cultured Cells. Retrieved online at: https://www.lifetechnologies.com/us/en/home/references/gibco-cell-culture-basics/cell-culture-protocols/maintaining-…
[cited by applicant]
[No Author Listed], NIH, Stem Cells: Scientific Progress and Future Research Directions. National Institutes of Health, Department of Health and Human Services. pp. 1-4, Jun. 2001.
[cited by applicant]
[No Author Listed], Pacific Blue anti-human CD41 antibody. BioLegend. Retrieved on Jul. 2, 2020. 6 pages. Accessible at https://www.biolegend.com/en-us/products/pacific-blue-anti-human-cd41-antibody-6994.
[cited by applicant]
[No Author Listed], PubChem CID 18068. Galactose-uridine-5′-diphosphate. Created Jun. 1, 2005. Last modified Aug. 27, 2022. Information retrieved from the internet: https://pubchem.ncbi.nlm.nih.gov/compound/Galactose-ur…
[cited by applicant]
[No Author Listed], UCLA, Induced Pluripotent Stem Cells (iPS). Definition.
[cited by applicant]
[No Author Listed], What is the difference between a leukocyte and a lymphocyte?. Socratic Q&A. Retrieved on Jul. 2, 2020. 1 page. Accessible at socratic.org/questions/what-is-the-difference-between-a-leukocyte-and-a-ly…
[cited by applicant]
Alikani et al., Nonviable human pre-implantation embryos as a source of stem cells for research and potential therapy. Stem Cell Rev. Dec. 2005;1(4):337-43.
[cited by applicant]
Amable et al., Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. Jun. 7, 2013;4(3):67. doi: 10.1186/scrt218.
[cited by applicant]
Amarilyo et al., Increased cord serum inflammatory markers in small-for-gestational-age neonates. J Perinatol. Jan. 2011;31(1):30-2. doi: 10.1038/jp.2010.53. Epub Apr. 22, 2010.
[cited by applicant]
Andreu et al., Prevention of HLA immunization with leukocyte-poor packed red cells and platelet concentrates obtained by filtration. Blood. Sep. 1988;72(3):964-9.
[cited by applicant]
Athanasiou et al., Increased expression of the ETS-related transcription factor FLI-1/ERGB correlates with and can induce the megakaryocytic phenotype. Cell Growth Differ. Nov. 1996;7(11):1525-34.
[cited by applicant]
Baek et al., Stroma-free mass production of clinical-grade red blood cells (RBCs) by using poloxamer 188 as an RBC survival enhancer. Transfusion. Nov. 2009;49(11):2285-95.
[cited by applicant]
Bagamery et al., Are platelets activated after a rapid, one-step density gradient centrifugation? Evidence from flow cytometric analysis. Clin Lab Haematol. Feb. 2005;27(1):75-7.
[cited by applicant]
Bertolini et al., Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients. Blood. Apr. 15, 1997;89(8):2679-88.
[cited by applicant]
Bhatia, Hematopoiesis from human embryonic stem cells. Ann N Y Acad Sci. Jun. 2007;1106:219-22.
[cited by applicant]
Bordoni et al., Hepatocyte-conditioned medium sustains endothelial differentiation of human hematopoietic-endothelial progenitors. Hepatology. May 2007;45(5):1218-28.
[cited by applicant]
Bowles et al., HOXB4 overexpression promotes hematopoietic development by human embryonic stem cells. Stem Cells. May 2006;24(5):1359-69.
[cited by applicant]
Brevini et al., No shortcuts to pig embryonic stem cells. Theriogenology. Sep. 1, 2010;74(4):544-50. doi: 10.1016/j.theriogenology.2010.04.020.
[cited by applicant]
Buta et al., Reconsidering pluripotency tests: do we still need teratoma assays? Stem Cell Res. Jul. 2013;11(1):552-62. doi: 10.1016/j.scr.2013.03.001. Review.
[cited by applicant]
Cerdan et al., Hematopoietic Differentiation. Embryonic Stem Cells. Chapter 5, pp. 53-83, (2007).
[cited by applicant]
Chadwick et al., Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. Blood. Aug. 1, 2003;102(3):906-15. Epub Apr. 17, 2003.
[cited by applicant]
Chang et al., Proplatelet formation is regulated by the Rho/ROCK pathway. Blood. May 15, 2007;109(10):4229-36. Epub Jan. 23, 2007.
[cited by applicant]
Chang et al., Definitive-like erythroid cells derived from human embryonic stem cells coexpress high levels of embryonic and fetal globins with little or no adult globin. Blood. Sep. 1, 2006;108(5):1515-23. Epub Apr. 27…
[cited by applicant]
Chan-Ling et al., Hematopoietic stem cells provide repair functions after laser-induced Bruch's membrane rupture model of choroidal neovascularization. Am J Pathol. Mar. 2006;168(3):1031-44.
[cited by applicant]
Chen et al., A point mutation in the integrin beta 3 cytoplasmic domain (S752-->P) impairs bidirectional signaling through alpha IIb beta 3 (platelet glycoprotein IIb-IIIa). Blood. Sep. 15, 1994;84(6):1857-65.
[cited by applicant]
Chen et al., Large generation of megakaryocytes from serum-free expanded human CD34+ cells. Biochem Biophys Res Commun. Jan. 2, 2009;378(1):112-7. doi: 10.1016/j.bbrc.2008.11.019. Epub Nov. 21, 2008.
[cited by applicant]
Cheng et al., Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34(+) hematopoietic progenitor cells. J Cell Physiol. Jul. 2000;184(1):58-69.
[cited by applicant]
Cho et al., A critical role for extracellular protein disulfide isomerase during thrombus formation in mice. J Clin Invest. Mar. 2008; 118(3):1123-31. doi: 10.1172/JCI34134.
[cited by applicant]
Cho et al., Enhancement of thrombogenesis by plasma fibronectin cross-linked to fibrin and assembled in platelet thrombi. Blood. May 1, 2006;107(9):3555-63. Epub Jan. 3, 2006.
[cited by applicant]
Chockalingam et al., Management of patients refractory to platelet transfusion. J Infus Nurs. Jul.-Aug. 2007;30(4):220-5. Review. Abstract Only.
[cited by applicant]
Choi et al., A common precursor for hematopoietic and endothelial cells. Development. Feb. 1998;125(4):725-32.
[cited by applicant]
Choi et al., In vitro development of a hemangioblast from a human embryonic stem cell, SNUhES#3. Life Sci. Jul. 3, 2009;85(1-2):39-45.
[cited by applicant]
Chun et al., Megakaryocyte Production from Feeder Cell-Free Cultures of Human Embryonic Stem Cells (hESC). Blood, 2009;114:Abstract 2528.
[cited by applicant]
Cibelli et al., Parthenogenetic stem cells in nonhuman primates. Science. Feb. 1, 2002;295(5556):819.
[cited by applicant]
Cibelli et al., Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development. ebiomed: The Journal of Regenerative Medicine. Nov. 26, 2001;2(5):25-31.
[cited by applicant]
Coller, Anti-GPIIb/IIIa drugs: current strategies and future directions. Thromb Haemost. Jul. 2001;86(1):427-43. Review. Abstract Only.
[cited by applicant]
Coppinger et al., Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood. Mar. 15, 2004;103(6):2096-104.
[cited by applicant]
Cortin et al., Efficient in vitro megakaryocyte maturation using cytokine cocktails optimized by statistical experimental design. Exp Hematol. Oct. 2005;33(10):1182-91.
[cited by applicant]
Dang et al., Efficiency of embryoid body formation and hematopoietic development from embryonic stem cells in different culture systems. Biotechnol Bioeng. 2002;78(4):442-453.
[cited by applicant]
Day et al., Murine thrombosis models. Thromb Haemost. Sep. 2004;92(3):486-94.
[cited by applicant]
Doe et al., Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. Jan. 2007;320(1):89-98. Epub Oct. 3, 2006.
[cited by applicant]
Dolzhanskiy et al., The development of human megakaryocytes: III. Development of mature megakaryocytes from highly purified committed progenitors in synthetic culture media and inhibition of thrombopoietin-induced polyp…
[cited by applicant]
Dore et al., Transcription factor networks in erythroid cell and megakaryocyte development. Blood. Jul. 14, 2011;118(2):231-9.
[cited by applicant]
Douay et al., Stem cells—a source of adult red blood cells for transfusion purposes: present and future. Crit Care Clin. Apr. 2009;25(2):383-98.
[cited by applicant]
Encabo et al., Interleukin-6 precludes the differentiation induced by interleukin-3 on expansion of CD34+ cells from cord blood. J Hematol. Apr. 2003;88(4):388-95.
[cited by applicant]
Falati et al., Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse. Nat Med. Oct. 2002;8(10):1175-81. Epub Sep. 16, 2002. Abstract only.
[cited by applicant]
Fan et al., Megakaryocyte Production From Feeder Cell-Free Cultures of Human Embryonic Stem Cells (hESC). Blood. 2009;114(22):2528. 3 pages.
[cited by applicant]
Fedele et al., CD38 is expressed on human mature monocyte-derived dendritic cells and is functionally involved in CD83 expression and IL-12 induction. Eur J Immunol. May 2004;34(5):1342-50.
[cited by applicant]
Feng et al., PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells. Proc Natl Acad Sci U S A. Apr. 22, 2008;105(16):6057-62. doi: 10.1073/pnas.0711961105.
[cited by applicant]
Feng et al., Scalable generation of universal platelets from human induced pluripotent stem cells. Stem Cell Reports. Nov. 11, 2014;3(5):817-31. doi: 10.1016/j.stemcr.2014.09.010. Epub Oct. 16, 2014.
[cited by applicant]
Figueiredo et al., Generation of HLA-deficient platelets from hematopoietic progenitor cells. Transfusion. Aug. 2010;50(8):1690-701. doi: 10.1111/j.1537-2995.2010.02644.x. Epub Apr. 15, 2010.
[cited by applicant]
Figueiredo et al., RNA Interference as a tool to reduce the risk of rejection in cell-based therapies. Intech Open Science. Chapter 15 from
[cited by applicant]
Fujiki et al., Role of human interleukin-9 as a megakaryocyte potentiator in culture. Exp Hematol. Dec. 2002;30(12):1373-80. Abstract only.
[cited by applicant]
Fujimoto et al., Production of functional platelets by differentiated embryonic stem (ES) cells in vitro. Blood. Dec. 1, 2003;102(12):4044-51. Epub Aug. 14, 2003.
[cited by applicant]
Fujimoto et al., Production of functional platelets by differentiated embryonic stem (ES) cells in vitro. Blood. Dec. 1, 2003;102(12):4044-51.
[cited by applicant]
Furie et al., In vivo thrombus formation. J Thromb Haemost. Jul. 2007;5 Suppl 1:12-7. Review.
[cited by applicant]
Furie et al., Mechanisms of thrombus formation. N Engl J Med. Aug. 28, 2008;359(9):938-49. doi: 10.1056/NEJMra0801082. Review. First 100 words only.
[cited by applicant]
Gaur et al., Megakaryocytes derived from human embryonic stem cells: a genetically tractable system to study megakaryocytopoiesis and integrin function. J Thromb Haemost. Feb. 2006;4(2):436-42.
[cited by applicant]
Geens et al., Human embryonic stem cell lines derived from single blastomeres of two 4-cell stage embryos. Hum Reprod. Nov. 2009;24(11):2709-17.
[cited by applicant]
Giammona et al., Nicotinamide (vitamin B3) increases the polyploidisation and proplatelet formation of cultured primary human megakaryocytes. Br J Haematol. Nov. 2006;135(4):554-66.
[cited by applicant]
Giarratana et al., Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells. Nat Biotechnol. Jan. 2005;23(1):69-74.
[cited by applicant]
Ginsberg et al., Inside-out integrin signaling. Curr Opin Cell Biol. Oct. 1992;4(5):766-71. Review. Abstract only.
[cited by applicant]
Gomez et al., Derivation of cat embryonic stem-like cells from in vitro-produced blastocysts on homologous and heterologous feeder cells. Theriogenology. Sep. 1, 2010;74(4):498-515. doi: 10.1016/j.theriogenology.2010.05…
[cited by applicant]
Grant et al., Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med. Jun. 2002;8(6):607-12.
[cited by applicant]
Gras, et al., HLA-universal platelet transfusions prevent platelet refractoriness in a mouse model. Hum Gene Ther. Dec. 2013;24(12):1018-28. doi: 10.1089/hum.2013.074. Epub Nov. 7, 2013.
[cited by applicant]
Guerriero et al., Stromal cell-derived factor 1alpha increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells. Blood. May 1, 2001;97(9):2587-95.
[cited by applicant]
Guo et al., c-Myc-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Blood. Sep. 3, 2009;114(10):2097-106. doi: 10.1182/blood-2009-01-197947.
[cited by applicant]
Guo et al., Hemangioblastic characteristics of fetal bone marrow-derived Flk1(+)CD31(−)CD34(−) cells. Exp Hematol. Jul. 2003;31(7):650-8.
[cited by applicant]
Hematti et al., Nonhuman primate embryonic stem cells as a preclinical model for hematopoietic and vascular repair. Exp Hematol. Sep. 2005;33(9):980-6.
[cited by applicant]
Hiroyama et al., Establishment of mouse embryonic stem cell-derived erythroid progenitor cell lines able to produce functional red blood cells. PLoS One. Feb. 6, 2008;3(2):e1544, 11 pages.
[cited by applicant]
Hod et al., Platelet transfusion refractoriness. Br J Haematol. Jul. 2008;142(3):348-60. doi: 10.1111/j.1365-2141.2008.07189.x. Epub May 28, 2008. Review.
[cited by applicant]
Hottz et al., Platelets in Immune Response to Virus and Immunopathology of Viral Infections. Front Med (Lausanne). Apr. 30, 2018;5:121. doi: 10.3389/fmed.2018.00121. eCollection 2018.
[cited by applicant]
Hu et al., Full reconstitution of human platelets in humanized mice after macrophage depletion. Blood. Aug. 23, 2012;120(8):1713-6. doi: 10.1182/blood-2012-01-407890. Epub Jul. 6, 2012.
[cited by applicant]
Huangfu et al., Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat Biotechnol. Nov. 2008;26(11):1269-75.
[cited by applicant]
Iacopetti et al., Application of Platelet-Rich Gel to Enhance Wound Healing in the Horse: A Case Report. J Equine Veterinary Sci. Aug. 2011; 1-6.
[cited by applicant]
Ireland, Visualizing Human Biology, 3rd Ed. Wiley and Sons Inc. 2008. 3 pages.
[cited by applicant]
Ishizaki et al., Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol. May 2000;57(5):976-83.
[cited by applicant]
Iwasaki et al., GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages. Immunity. Sep. 2003;19(3):451-62.
[cited by applicant]
Jarnjak-Jankovic et al., A full scale comparative study of methods for generation of functional Dendritic cells for use as cancer vaccines. BMC Cancer. Jul. 3, 2007;7:119. 9 pages.
[cited by applicant]
Jean et al., Pluripotent genes in avian stem cells. Dev Growth Differ. Jan. 2013;55(1):41-51. doi: 10.1111/dgd.12021. Review.
[cited by applicant]
Jeanpierre et al., BMP4 regulation of human megakaryocytic differentiation is involved in thrombopoietin signaling. Blood. Oct. 15, 2008;112(8):3154-63. doi: 10.1182/blood-2008-03-145326. Epub Jul. 29, 2008.
[cited by applicant]
Junt et al., Dynamic visualization of thrombopoiesis within bone marrow. Science. Sep. 21, 2007;317(5845):1767-70.
[cited by applicant]
Kanaji et al., Megakaryocyte proliferation and ploidy regulated by the cytoplasmic tail of glycoprotein Ibalpha. Blood. Nov. 5, 2004;104(10):3161-8.
[cited by applicant]
Karsunky et al., Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo. J Exp Med. 2003;198(2):305-13.
[cited by applicant]
Kaufman et al., Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A. Sep. 11, 2001;98(19):10716-21. Epub Sep. 4, 2001.
[cited by applicant]
Kennedy et al., Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures. Blood. Apr. 1, 2007;109(7):2679-87.
[cited by applicant]
Khan et al., New strategies in acute myeloid leukemia: redefining prognostic markers to guide therapy. Clin Cancer Res. Oct. 1, 2012;18(19):5163-71. doi: 10.1158/1078-0432.CCR-12-0313. Epub Aug. 14, 2012.
[cited by applicant]
Kimura et al., Interleukin 6 is a differentiation factor for human megakaryocytes in vitro. Eur J Immunol. 1990;20:1927-31.
[cited by applicant]
Klimanskaya et al., Approaches for Derivation and Maintenance of Human Embryonic Stem Cells: Detailed Procedures and Alternatives. Essentials of Stem Cell Biology, Third Edition. Academic Press. Chapter 29, pp. 409-434,…
[cited by applicant]
Klimanskaya et al., Approaches for Derivation and Maintenance of Human ES Cells: Detailed Procedures and Alternatives. Handbook of Stem Cells. Elsevier Academic Press, Amsterdam. vol. 1, Embryonic Stem Cells. Robert Lan…
[cited by applicant]
Klimanskaya et al., Approaches of derivation and maintenance of human ES cells: Detailed procedures and alternatives. vol. 1: Embryonic Stem Cells. New York: Elsevier/Academic Press; 2004:437-49.
[cited by applicant]
Klimchenko et al., A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis. Blood. Aug. 2009 0;114(8):1506-17. doi:10.1182/blood-2008-09-178…
[cited by applicant]
Kuter, New thrombopoietic growth factors. Blood. Jun. 1, 2007;109(11):4607-16. Epub Feb. 8, 2007. Review.
[cited by applicant]
Lagrue-Lak-Hal et al., Expression and function of the collagen receptor GPVI during megakaryocyte maturation. J Biol Chem. May 4, 2001;276(18):15316-25.
[cited by applicant]
Lalezari et al., Ability of thrombocytes to acquire HLA specificity from plasma. Blood. Jan. 1982;59(1):167-70.
[cited by applicant]
Lane et al., Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood. Dec. 15, 2000;96(13):4152-9.
[cited by applicant]
Larson et al., Regulation of proplatelet formation and platelet release by integrin alpha IIb beta3. Blood. Sep. 1, 2006;108(5):1509-14. Epub May 2, 2006.
[cited by applicant]
Law et al., Analysis of human megakaryocytic cells using dual-color immunofluorescence labeling. Cytometry. Dec. 1, 2000;41(4):308-15.
[cited by applicant]
Lechmann et al., CD83 on dendritic cells: more than just a marker for maturation. Trends Immunol. Jun. 2002;23(6):273-5.
[cited by applicant]
Ledran et al., Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches. Cell Stem Cell. Jul. 3, 2008;3(1):85-98. doi: 10.1016/j.stem.2008.06.001.
[cited by applicant]
Li et al., [In vitro differentiation into megakaryocytes and generation of platelets from CD34+ cells of umbilical cord blood]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. Oct. 2006;31(5):776-81. Chinese.
[cited by applicant]
Li et al., Large scale generation of functional megakaryocytes from human embryonic stem cells (hESCs) under stromal-free conditions. Blood. 2009;114;2540. Abstract 2540. 4 pages.
[cited by applicant]
Lin et al., Multilineage potential of homozygous stem cells derived from metaphase II oocytes. Stem Cells. 2003;21(2):152-61.
[cited by applicant]
Loges et al., Identification of the adult human hemangioblast. Stem Cells Dev. Jun. 2004; 13(3):229-42.
[cited by applicant]
Lordier et al., Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling. Blood. Oct. 15, 2008;112(8):3164-74. doi: 10.1182/blood-2008-03-144956. Epub …
[cited by applicant]
Lowry et al., Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A. Feb. 26, 2008;105(8):2883-8. doi: 10.1073/pnas.0711983105. Epub Feb. 15, 2008.
[cited by applicant]
Lu et al., Biologic properties and enucleation of red blood cells from human embryonic stem cells. Blood. Dec. 1, 2008;112(12):4475-84. doi: 10.1182/blood-2008-05-157198. Epub Aug. 19, 2008.
[cited by applicant]
Lu et al., CD34+CD38− hematopoietic precursors derived from human embryonic stem cells exhibit an embryonic gene expression pattern. Blood. Jun. 1, 2004;103(11):4134-41. Epub Feb. 12, 2004.
[cited by applicant]
Lu et al., GeneChip analysis of human embryonic stem cell differentiation into hemangioblasts: an in silico dissection of mixed phenotypes. Genome Biol. 2007;8(11):R240, 19 pages.
[cited by applicant]
Lu et al., Generation of functional hemangioblasts from human embryonic stem cells. Nat Methods. Jun. 2007;4(6):501-9. Epub May 7, 2007.
[cited by applicant]
Lu et al., Hemangioblasts from human embryonic stem cells generate multilayered blood vessels with functional smooth muscle cells. Regen Med. Jan. 2009;4(1):37-47.
[cited by applicant]
Lu et al., Megakaryocyte developmental biology platelet production regulatory system. International Journal of Blood Transfusion and Hematology. 2012; 1: 66-69.
[cited by applicant]
Lu et al., Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice. Cell Res. Mar. 2011;21(3):530-45. doi: 10.1038/cr.2011.8. Epub Jan. 11, 2011.
[cited by applicant]
Lu et al., Protocol for culturing, differentiating and expanding hES-BC cells. Supplemental Protocol. Nature Methods. 2007;4:1-3.
[cited by applicant]
Lu et al., Recombinant HoxB4 fusion proteins enhance hematopoietic differentiation of human embryonic stem cells. Stem Cells Dev. Aug. 2007;16(4):547-59.
[cited by applicant]
Lu et al., Robust generation of hemangioblastic progenitors from human embryonic stem cells. Regen Med. Sep. 2008;3(5):693-704. doi: 10.2217/17460751.3.5.693.
[cited by applicant]
Luo et al., Role of Blood Flow Shear Stress in Atherosclerosis. China Modern Doctor. 2010; 9:13-14,47.
[cited by applicant]
Ma et al., Generation of functional erythrocytes from human embryonic stem cell-derived definitive hematopoiesis. Proc Natl Acad Sci U S A. Sep. 2, 2008;105(35):13087-92.
[cited by applicant]