Stem cells and regenerative medicine: Accomplishments to date and future promise

Therapeutic Delivery

Volumn 1, Issue 5, 2010, Pages 693-705

  Helmy, Karim Y ^a,b,c   Patel, Shyam A ^a,b   Silverio, Kimberly ^a   Pliner, Lillian ^a   Rameshwar, Pranela ^a  

^a RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY   (United States)

^c MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNITY; ADULT STEM CELL; ALLOGENEIC STEM CELL TRANSPLANTATION; AUTOTRANSPLANTATION; CARCINOGENESIS; CELL HOMING; EMBRYONIC STEM CELL; FETAL STEM CELL; GRAFT REJECTION; GRAFT VERSUS HOST REACTION; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNOGENICITY; IMMUNOMODULATION; INNATE IMMUNITY; MESENCHYMAL STEM CELL; MESENCHYMAL STEM CELL TRANSPLANTATION; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REGENERATIVE MEDICINE; REVIEW; TISSUE REGENERATION;

EID: 79954492139     PISSN: 20415990     EISSN: 20416008     Source Type: Journal    
DOI: 10.4155/tde.10.57     Document Type: Review

References (104)

1. Alison MR, Islam S. Attributes of adult stem cells. J. Pathol. 217(2), 144-160 (2009).
2. Thomas ED, Lochte HL Jr, Cannon JH, Sahler OD, Ferrebee JW. Supralethal whole body irradiation and isologous marrow transplantation in man. J. Clin. Invest. 38, 1709-1716 (1959).
3. O'Reilly RJ, Dupont B, Pahwa S, et al. Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. N. Engl. J. Med. 297(24), 1311-1318 (1977). (Pubitemid 8249122)
4. McCullough J, Perkins HA, Hansen J. The National Marrow Donor Program with emphasis on the early years. Transfusion 46(7), 1248-1255 (2006). (Pubitemid 44139501)
5. Li M, Sun K, Welniak LA, Murphy WJ. Immunomodulation and pharmacological strategies in the treatment of graft-versus-host disease. Expert Opin. Pharmacother. 9(13), 2305-2316 (2008).
6. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 112(12), 4371-4383 (2008).
7. Molineux G, Pojda Z, Hampson IN, Lord BI, Dexter TM. Transplantation potential of peripheral blood stem cells induced by granulocyte colony-stimulating factor. Blood 76(10), 2153-2158 (1990).
8. Beshlawy AE, Metwally HG, Khalek KA, Hammoud RF, Mousa SM. The effect of freezing on the recovery and expansion of umbilical cord blood hematopoietic stem cells. Exp. Clin. Transplant 7(1), 50-55 (2009).
9. Jenq RR, van den Brink MR. Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nat. Rev. Cancer 10(3), 213-221 (2010).
10. Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLAidentical relatives in patients with hematologic cancers. N. Engl. J. Med. 344(3), 175-181 (2001). (Pubitemid 32064138)
11. Cutler C, Giri S, Jeyapalan S, et al. Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J. Clin. Oncol. 19(16), 3685-3691 (2001). (Pubitemid 32786281)
12. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 282(5391), 1145-1147 (1998). (Pubitemid 28516247)
13. Gerrard L, Zhao D, Clark AJ, Cui W. Stably transfected human embryonic stem cell clones express OCT4-specific green fluorescent protein and maintain self-renewal and pluripotency. Stem Cells 23(1), 124-133 (2005). (Pubitemid 40105298)
14. Bonner-Weir S. Stem cells in diabetes: what has been achieved. Horm. Res. 60 (Suppl. 3),(2003).
15. Schwanke K, Wunderlich S, Reppel M, et al. Generation and characterization of functional cardiomyocytes from rhesus monkey embryonic stem cells. Stem Cells 24(6), 1423-1432 (2006). (Pubitemid 44464658)
16. Nieden NI, Kempka G, Ahr HJ. In vitro differentiation of embryonic stem cells into mineralized osteoblasts. Differentiation 71(1), 18-27 (2003). (Pubitemid 38230416)
17. Andrews PW, Matin MM, Bahrami AR, et al. Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin. Biochem. Soc. Trans. 33, 1526-1530 (2005). (Pubitemid 41779730)
18. Keirstead HS, Nistor G, Bernal G, et al. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J. Neurosci. 25(19), 4694-4705 (2005). (Pubitemid 40664118)
19. Druml C. Stem cell research: toward greater unity in Europe? Cell 139(4), 649-651 (2009).
20. Dhar D, Hsi-En Ho J. Stem cell research policies around the world. Yale J. Biol. Med. 82(3), 113-115 (2009).
21. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663-676 (2006). (Pubitemid 44233629)
22. Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858), 1917-1920 (2007).
23. Kang L, Kou Z, Zhang Y, Gao S. Induced pluripotent stem cells (iPSCs) - a new era of reprogramming. J. Genet. Genomics 37(7), 415-421 (2010).
24. Reinisch A, Strunk D. Isolation and animal serum free expansion of human umbilical cord derived mesenchymal stromal cells (MSCs) and endothelial colony forming progenitor cells (ECFCs). J. Vis. Exp. DOI: 10.3791/1525 (2009) (Online only).
25. Jager M, Zilkens C, Bittersohl B, Krauspe R. Cord blood - an alternative source for bone regeneration. Stem Cell Rev. 5(3), 266-277 (2009).
26. Zeddou M, Briquet A, Relic B, et al. The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood. Cell Biol. Int. 34(7), 693-701 (2010).
27. Magatti M, De Munari S, Vertua E, et al. Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. Stem Cells 26(1 182-192 (2008).
28. Chong MS, Chan J. Lentiviral vector transduction of fetal mesenchymal stem cells. Methods Mol. Biol. 614, 135-147 (2010).
29. Rameshwar P. Casting doubt on the safety of 'off-the-shelf' mesenchymal stem cells for cell therapy. Mol. Ther. 17(2), 216-218 (2009).
30. Eapen M, Rubinstein P, Zhang MJ, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 369(9577), 1947-1954 (2007). (Pubitemid 46874578)
31. Reimann V, Creutzig U, Kogler G. Stem cells derived from cord blood in transplantation and regenerative medicine. Dtsch. Arztebl. Int. 106(50), 831-836 (2009).
32. Gotherstrom C, Ringden O, Tammik C, et al. Immunologic properties of human fetal mesenchymal stem cells. Am. J. Obstet. Gynecol. 190(1), 239-245 (2004). (Pubitemid 38156354)
33. Neri M, Maderna C, Ferrari D, et al. Robust generation of oligodendrocyte progenitors from human neural stem cells and engraftment in experimental demyelination models in mice. PLoS One 5(4), e10145 (2010).
34. Todorov P, Hristova E, Konakchieva R, Michova A, Dimitrov J. Comparative studies of different cryopreservation methods for mesenchymal stem cells derived from human fetal liver. Cell Biol. Int. 34(5), 455-462 (2010).
35. Barker JN, Rocha V, Scaradavou A. Optimizing unrelated donor cord blood transplantation. Biol. Blood Marrow Transplant. 15, 154-161 (2009).
36. Karanes C, Nelson GO, Chitphakdithai P, et al. Twenty years of unrelated donor hematopoietic cell transplantation for adult recipients facilitated by the National Marrow Donor Program. Biol. Blood Marrow Transplant. 14, 8-15 (2008).
37. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation 17(4), 331-340 (1974).
38. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7(2), 211-228 (2001). (Pubitemid 32295155)
39. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl Acad. Sci. USA 97(25), 13625-13630 (2000).
40. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 284(5411), 143-147 (1999). (Pubitemid 29282067)
41. Cho KJ, Trzaska KA, Greco SJ, et al. Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 a. Stem Cells 23(3), 383-391 (2005). (Pubitemid 40404457)
42. Kopen GC, Prockop DJ, Phinney DG. 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(19), 10711-10716 (1999). (Pubitemid 29442209)
43. Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science 284(5417), 1168-1170 (1999). (Pubitemid 29288406)
44. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4), 315-317 (2006). (Pubitemid 44269669)
45. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24(5), 1294-1301 (2006). (Pubitemid 44464698)
46. Lepperdinger G, Brunauer R, Jamnig A, Laschober G, Kassem M. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp. Gerontol. 43(11), 1018-1023 (2008).
47. Alviano F, Fossati V, Marchionni C, et al. Term amniotic membrane is a high throughput source for multipotent mesenchymal stem cells with the ability to differentiate into endothelial cells in vitro. BMC Dev. Biol. 7, 11 (2007).
48. Potapova IA, Brink PR, Cohen IS, Doronin SV. Culturing of human mesenchymal stem cells as three-dimensional aggregates induces functional expression of CXCR4 that regulates adhesion to endothelial cells. J. Biol. Chem. 283(19), 13100-13107 (2008).
49. Izadpanah R, Kaushal D, Kriedt C, et al. Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Res. 68(11), 4229-4238 (2008).
50. Wagner W, Horn P, Castoldi M, et al. Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One 3(5), e2213 (2008).
51. Stolzing A, Jones E, McGonagle D, Scutt A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech. Ageing Dev. 129(3), 163-173 (2008).
52. Dumont RJ, Dayoub H, Li JZ, et al. Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents. Neurosurgery 51(5), 1239-1244; discussion 1244-1245 (2002).
53. El-Badri NS, Hakki A, Ferrari A, Shamekh R, Good RA. Autoimmune disease: is it a disorder of the microenvironment? Immunol. Res. 41(1), 79-86 (2008). (Pubitemid 351903814)
54. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp. Hematol. 30(1), 42-48 (2002). (Pubitemid 34059216)
55. Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363(9419), 1439-1441 (2004). (Pubitemid 38586721)
56. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 110(10), 3499-3506 (2007). (Pubitemid 350159613)
57. Rossignol J, Boyer C, Thinard R, et al. Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation. J. Cell. Mol. Med. 13(8B), 2547-2558 (2009).
58. Castillo MD, Trzaska KA, Greco SJ, Ponzio NM, Rameshwar P. Immunostimulatory effects of mesenchymal stem cell-derived neurons: implications for stem cell therapy in allogeneic transplantations. Clin. Transl. Sci. 1(1), 27-34 (2008).
59. Almeida-Porada G, Porada CD, Tran N, Zanjani ED. Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation. Blood 95(11), 3620-3627 (2000). (Pubitemid 30428501)
60. Pereira RF, Halford KW, O'Hara MD, et al. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc. Natl Acad. Sci. USA 92(11), 4857-4861 (1995).
61. Horwitz EM, Prockop DJ, Fitzpatrick LA, et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat. Med. 5(3), 309-313 (1999). (Pubitemid 29124367)
62. Horwitz EM, Gordon PL, Koo WKK, et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc. Natl Acad. Sci. USA 99(13), 8932-8937 (2002). (Pubitemid 34693661)
63. Pochampally RR, Horwitz EM, DiGirolamo CM, Stokes DS, Prockop DJ. Correction of a mineralization defect by overexpression of a wild-type cDNA for COL1A1 in marrow stromal cells (MSCs) from a patient with osteogenesis imperfecta: a strategy for rescuing mutations that produce dominant-negative protein defects. Gene. Ther. 12(14), 1119-1125 (2005). (Pubitemid 41030617)
64. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature 410(6829), 701-705 (2001). (Pubitemid 32290358)
65. Nishiyama N, Miyoshi S, Hida N, et al. The significant cardiomyogenic potential of human umbilical cord blood-derived mesenchymal stem cells in vitro. Stem Cells 25(8), 2017-2024 (2007). (Pubitemid 47258179)
66. Walther G, Gekas J, Bertrand OF. Amniotic stem cells for cellular cardiomyoplasty: promises and premises. Catheter. Cardiovasc. Interv. 73(7), 917-924 (2009).
67. Sodian R, Schaefermeier P, Abegg-Zips S, et al. Use of human umbilical cord blood-derived progenitor cells for tissue-engineered heart valves. Ann. Thorac. Surg. 89(3), 819-828 (2010).
68. Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99(10), 3838-3843 (2002). (Pubitemid 34534559)
69. Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105(1), 4120-4126 (2005). (Pubitemid 40656164)
70. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J. Immunol. 177(4), 2080-2087 (2006). (Pubitemid 44200965)
71. Spaggiari GM, Capobianco A, Becchetti S, Mingari MC, Moretta L. Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2- induced NK-cell proliferation. Blood 107(4), 1484-1490 (2006). (Pubitemid 43242385)
72. Selmani Z, Naji A, Zidi I, et al. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 26(1), 212-222 (2008).
73. Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 107(1), 367-372 (2006). (Pubitemid 43053565)
74. Rasmusson I, Le Blanc K, Sundberg B, Ringden O. Mesenchymal stem cells stimulate antibody secretion in human B cells. Scand. J. Immunol. 65(4), 336-343 (2007). (Pubitemid 46481102)
75. Togel F, Hu Z, Weiss K, et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am. J. Physiol. Renal Physiol. 289(1), F31-42 (2005). (Pubitemid 40863570)
76. Figliuzzi M, Cornolti R, Perico N, et al. Bone marrow-derived mesenchymal stem cells improve islet graft function in diabetic rats. Transplant Proc. 41(5), 1797-1800 (2009).
77. Qiao L, Xu Z, Zhao T, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 18(4), 500-507 (2008). (Pubitemid 351498857)
78. Kidd S, Spaeth E, Dembinski JL, et al. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 27(10), 2614-2623 (2009).
79. Grayson WL, Zhao F, Bunnell B, Ma T. Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells. Biochem. Biophys. Res. Commun. 358(3), 948-953 (2007). (Pubitemid 46802482)
80. Birnbaum T, Roider J, Schankin CJ, et al. Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. J. Neurooncol. 83(3), 241-247 (2007). (Pubitemid 46952234)
81. Nakamizo A, Marini F, Amano T, et al. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res. 65(8), 3307-3318 (2005). (Pubitemid 40524615)
82. Studeny M, Marini FC, Dembinski JL, et al. Mesenchymal stem cells: potential precursors for tumor stroma and targeteddelivery vehicles for anticancer agents. J. Natl Cancer Inst. 96(21), 1593-1603 (2004). (Pubitemid 39534883)
83. Studeny M, Marini FC, Champlin RE, et al. Bone marrow-derived mesenchymal stem cells as vehicles for interferon-b delivery into tumors. Cancer Res. 62(13), 3603-3608 (2002). (Pubitemid 34728832)
84. Xin H, Kanehira M, Mizuguchi H, et al. Targeted delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells. Stem Cells 25(7), 1618-1626 (2007). (Pubitemid 47121838)
85. Kim SM, Lim JY, Park SI, et al. Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma. Cancer Res. 68(23), 9614-9623 (2008).
86. Loebinger MR, Eddaoudi A, Davies D, Janes SM. Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res. 69(10), 4134-4142 (2009).
87. Grisendi G, Bussolari R, Cafarelli L, et al. Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res. 70(9), 3718-3729.
88. Behr L, Hekmati M, Lucchini A, et al. Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury. Cell. Prolif. 42(3), 284-297 (2009).
89. Tatsumi K, Otani H, Sato D, et al. Granulocyte-colony stimulating factor increases donor mesenchymal stem cells in bone marrow and their mobilization into peripheral circulation but does not repair dystrophic heart after bone marrow transplantation. Circ. J. 72(8), 1351-1358 (2008).
90. Amariglio N, Hirshberg A, Scheithauer BW, et al. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med. 6(2), e1000029 (2009).
91. Rubio D, Garcia-Castro J, Martin MC, et al. Spontaneous human adult stem cell transformation. Cancer Res. 65(8), 3035-3039 (2005). (Pubitemid 40524580)
92. Bernardo ME, Zaffaroni N, Novara F, et al. Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res. 67, 9142-9149 (2007). (Pubitemid 47535900)
93. Sawada R, Ito T, Tsuchiya T. Changes in expression of genes related to cell proliferation in human mesenchymal stem cells during in vitro culture in comparison with cancer cells. J. Artif. Organs 9(3), 179-184 (2006). (Pubitemid 44453868)
94. Wang Y, Huso DL, Harrington J, et al. Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy 7(6), 509-519 (2005). (Pubitemid 43078081)
95. Rubio D, Garcia S, Paz MF, et al. Molecular characterization of spontaneous mesenchymal stem cell transformation. PLoS One 3(1), e1398 (2008).
96. Rubio D, Garcia S, De la Cueva T, et al. Human mesenchymal stem cell transformation is associated with a mesenchymal-epithelial transition. Exp. Cell Res. 314(4), 691-698 (2008).
97. Moioli EK, Hong L, Guardado J, Clark PA, Mao JJ. Sustained release of TGFb3 from PLGA microspheres and its effect on early osteogenic differentiation of human mesenchymal stem cells. Tissue Eng. 12(3), 537-546 (2006). (Pubitemid 43673459)
98. Sumanasinghe RD, Osborne JA, Loboa EG. Mesenchymal stem cell-seeded collagen matrices for bone repair: effects of cyclic tensile strain, cell density, and media conditions on matrix contraction in vitro. J. Biomed. Mater. Res. A 88(3), 778-786 (2009).
99. Schneider OD, Loher S, Brunner TJ, et al. Cotton wool-like nanocomposite biomaterials prepared by electrospinning: in vitro bioactivity and osteogenic differentiation of human mesenchymal stem cells. J. Biomed. Mater. Res. B Appl. Biomater. 84(2), 350-362 (2008).
100. Plotnikov AN, Schlapakova I, Szabolcs MJ, et al. Xenografted adult human mesenchymal stem cells provide a platform for sustained biological pacemaker function in canine heart. Circulation 116(7), 706-713 (2007). (Pubitemid 47255987)
101. Wagner J, Kean T, Young R, Dennis JE, Caplan AI. Optimizing mesenchymal stem cell-based therapeutics. Curr. Opin. Biotechnol. 20(5), 531-536 (2009).
102. US Department of Health and Human Services, Office of Extramural Research. http://grants.nih.gov/stem-cells/registry/current.htm
103. International Society for Stem Cell Research, international legislation. www.isscr.org/public/regions/index.cfm
104. US National Institutes of Health, clinical trials registry. www.clinicaltrials.gov