KSBB Journal

The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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The Use of Stem Cells as Medical Therapy

줄기세포를 이용한 세포치료법

  • Son Eun-Hwa (Dept. of Pharmacognosy Material Development, Samcheok National University) ;
  • Pyo Suhkneung (Division of Immunopharmacology, College of Pharmacy, Sungkyunkwan University)
  • 손은화 (삼척국립대학교 생약자원개발학과) ;
  • 표석능 (성균관대학교 약학부)
  • Published : 2005.02.01
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Abstract

Recently, there has been extremely active in the research of stem cell biology. Stem cells have excellent potential for being the ultimate source of transplantable cells for many different tissues. Researchers hope to use stem cells to repair or replace diseased or damaged organs, leading to new treatments for human disorders that are currently incurable, including diabetes, spinal cord injury and brain diseases. There are primary sources of stem cells like embryonic stem cells and adult stem cells. Stem cells from embryos were known to give rise to every type of cell. However, embryonic stem cells still have a lot of disadvantages. First, transplanted cells sometimes grow into tumors. Second, the human embryonic stem cells that are available for research would be rejected by a patient's immune system. Tissue-matched transplants could be made by either creating a bank of stem cells from more human embryos, or by cloning a patient's DNA into existing stem cells to customize them. However, this is laborious and ethically contentious. These problems could be overcome by using adult stem cells, taken from a patient, that are treated to remove problems and then put back. Nevertheless, some researchers do not convince that adult stem cells could, like embryonic ones, make every tissue type. Human stem cell research holds enormous potential for contributing to our understanding of fundamental human biology. In this review, we discuss the recent progress in stem cell research and the future therapeutic applications.

Keywords

References

  1. Weissman, I. L. (2000), Translating stem and progenitor cell biology to the clinic: barriers and opportunities, Science, 287, 1442-1446 https://doi.org/10.1126/science.287.5457.1442
  2. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S. and J. M. Jones (1998), Embryonic stem cell lines derived from human blastocysts, Science, 282, 1145-1147 https://doi.org/10.1126/science.282.5391.1145
  3. Reubinoff, B. E., Pera, M. F., Fong, C. Y., Trounson, A. and A. Bongso (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro, Nat. Biotechnol., 18, 399-404 https://doi.org/10.1038/74447
  4. Shamblott, M. J., Axelman, J., Wang, S., Bugg, E. M., Littlefield, J. W., Donovan, P. J., Blumenthal, P. D., Huggins, G. R. and J. D. Gearhart (1998), Derivation of pluripotent stem cells from cultured human primordial germ cells, Proc. Natl. Acad. Sci., 95, 13726-13731
  5. Spangrude, G. J., Heimfeld, S. and I. L. Weissman (1998), Purification and characterization of mouse hematopoietic stem cells, Science, 241, 58-62
  6. Bhatia, M., Wang, J. C., Kapp, U., Bonnet, D. and J. E. Dick (1997), Purification of primitive human hematopoietic cells capable of repopulating innnune-deficient mice, Proc. Nail. Acad. Sci. USA, 94, 5320-5325
  7. Low, W. C., Largaespada, D. A. and C. M. Verfaillie (2002), Pluripotency of mesenchymal stem cells derived from adult marrow, Nature, 418, 41-49 https://doi.org/10.1038/nature00870
  8. Verfaillie, C. M. (2002), Adult stem cells: Assessing the case for pluripotency, Trends Cell Biol. 12, 502-508 https://doi.org/10.1016/S0962-8924(02)02386-3
  9. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S. and D. R. Marshak (1999), Multilineage potential of adult human mesenchymal stem cells, Science, 284, 143-147 https://doi.org/10.1126/science.284.5411.143
  10. Woodbury, D., Reynolds, K. and I. B. Black (2002), Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis, J. Neurosci. Res. 69, 908-917 https://doi.org/10.1002/jnr.10365
  11. Alison, M. R., Poulsom, R., Otto, W. R., Vig, P., Brittan, M., Direkze, N. C., Preston, S. L. and N. A. Wright (2003), Plastic adult stem cells: Will they graduate from the school of hard knocks? J. Cell Sci. 116, 599-603 https://doi.org/10.1242/jcs.00269
  12. Eiges, R. (2001), Establishment of human embryonic stem cell transfected clones carrying a marker for undifferentiated cells, Curr. BioI. 11, 514-518 https://doi.org/10.1016/S0960-9822(01)00144-0
  13. Kawase, E. (2000), Mouse embryonic stem (ES) cell lines established from neuronal cell-derived cloned blastocysts, Genesis, 28, 156-163 https://doi.org/10.1002/1526-968X(200011/12)28:3/4<156::AID-GENE100>3.0.CO;2-T
  14. Palmer, T., Schwartz, P. H., Taupin, P., Kaspar, B., Stein, S. A. and F. H. Gage (2001), Progenitor cells from human brain after death, Nature, 411, 42-43 https://doi.org/10.1038/35075141
  15. Kimber, S. J. (2000), Molecular interactions at the maternalembryonic interface during the early phase of implantation, Semin. Reprod. Med. 18, 237-253 https://doi.org/10.1055/s-2000-12562
  16. Itskovitz-Eldor, J. (2000), Differentiation of human embryonic stem cells into embryoid bodies comprising the three embryonic germ layers, Mol. Med. 6, 88-95
  17. Maeshak, D. R. and Gardner, R. L. (2001), Stem Cell Biology(Monograph 40), p550, Cold Spring Harbor Lab. Press
  18. Lanzendorf, S. E. (2002), Human Gametes Obtained from Anonymous Donors for the Production of Human Embryonic Stem Cell Lines, Obst. Gynecol Surv. 57, 34-35 https://doi.org/10.1097/00006254-200201000-00019
  19. Greider, C. (1998), Telomeres and senescence: the history, the experiment, the future, Curr. Biol. 8, 178-181 https://doi.org/10.1016/S0960-9822(98)70105-8
  20. Hodes, R. J. (1999), Telomere length, aging, and somatic cell turnover, J. Exp. Med. 190, 153-156 https://doi.org/10.1084/jem.190.2.153
  21. Evans, M. J. and M. H. Kaufman (1981), Establishment in culture of pluripotential cells from mouse embryos, Nature, 292, 154-156 https://doi.org/10.1038/292154a0
  22. Martin, G. R. (1981), Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells, Proc. Natl. Acad. Sci. USA, 78, 7634 - 7638
  23. Braude, P., Bolton, V. and S. Moore (1988), Human gene expression first occurs between the four-and eight-cell stages of preimplantation development, Nature, 332, 459-461 https://doi.org/10.1038/332459a0
  24. Kaufman, M. H. (1992), The atlas of mouse development, Academic Press. London
  25. Luckett, W. P. (1975), The development of primordial and defmitive amniotic cavities in early Rhesus monkey and human embryos, J. Anat. 144, 149-167 https://doi.org/10.1002/aja.1001440204
  26. Luckett, W. P. (1978), Origin and differentiation of the yolk sac and exttaembryonic mesoderm in presomite human and rhesus monkey embryos, J. Anat. 152, 59-97 https://doi.org/10.1002/aja.1001520106
  27. O'Rahilly, R. and F. Muller (1992), Human embryology and teratology, Wiley-Liss, New York
  28. Solter, D. and B. B. Knowles (1978), Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1), Proc. Natl. Acad. Sci. USA, 75, 5565-5569
  29. Starr, R., Novak, U., Willson, T. A., Inglese, M., Murphy, V., Alexander, W. S., Metcalf, D., Nicola, N. A., Hilton, D. J. and M. Ernst (1997), Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction, J. Biol Chem. 272, 19982-19986 https://doi.org/10.1074/jbc.272.32.19982
  30. Niwa, H. B. T., Chambers, I. and A. Smith (1998), Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3, Gene Dev. 12, 2048-2060 https://doi.org/10.1101/gad.12.13.2048
  31. Burdon, T., Smith, A. and P. Savatier (2002), Signalling, cell cycle and pluripotency in embryonic stem cells, Trend Cell BioI. 12, 432 https://doi.org/10.1016/S0962-8924(02)02352-8
  32. Schuldiner, M., Yanuka, O., Itskovitz-Eldor, J., Melton, D. A. and N. Benvenisty (2000), Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells, Proc. Natl. Acad. Sci. USA, 97, 11307-11312
  33. Assady, S., Maor, G., Amit, M., Itskovitz-Eldor, J., Skorecki, K. L. and M. Tzukerman (2001), Insulin production by human embryonic stem cells, Diabetes, 50, 1691-1697 https://doi.org/10.2337/diabetes.50.8.1691
  34. Kehat, I., Kenyagin-Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J. and L. Gepstein (2001), Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes, J. Clin. Invest. 108, 407-414 https://doi.org/10.1172/JCI200112131
  35. Kaufman, D. S., Hanson, E. T., Lewis, R. L., Auerbach, R. and J. A. Thomson (2001), Hematopoietic colony- forming cells derived from human embryonic stem cells, Proc. Natl. Acad. Sci. USA, 98, 10716-10721
  36. Reubinoff, B. E., Itsykson, P., Turetsky, T., Pera, M. F., Reinhattz, E., Itzik, A. and T. Ben-Hur (2001), Neural progenitors from human embryonic stem cells, Nat. Biotechnol. 19, 1134-1140 https://doi.org/10.1038/nbt1201-1134
  37. Zhang, S. C., Wemig, M., Duncan, I. D., Brustle, O. and J. A. Thomson (2001), In vitro differentiation of transplantable neural precursors from human embryonic stem cells, Nat. Biotechnol., 19, 1129-1133 https://doi.org/10.1038/nbt1201-1129
  38. Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S. and A. Smith (2003), Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells, Cell, 113, 643-655 https://doi.org/10.1016/S0092-8674(03)00392-1
  39. Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., Maruyama, M, Maeda, M. and S. Yamanaka, (2003), The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells, Cell, 113, 631-642 https://doi.org/10.1016/S0092-8674(03)00393-3
  40. Kim, J. H., Auerbach, J. M., Rodriguez-Gomez, J. A., Velasco, I., Gavin, D., Lumelsky, N., Lee, S. H., Nguyen, J., Sanchez-Pemaute, R., Bankiewicz, K. and R. McKay (2002), Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease, Nature, 418, 50-56 https://doi.org/10.1038/nature00900
  41. Kodama, S., Kuhtreiber, W., Fujimura, S., Dale, E. A. and D. L. Faustman (2003), Islet regeneration during the reversal of autoimmune diabetes in NOD mice, Science, 302, 1223-1227 https://doi.org/10.1126/science.1088949
  42. Shake, J. G. (2002), Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftrnent and functional effects, Ann. Thorac. Surg. 73, 1919-1925 https://doi.org/10.1016/S0003-4975(02)03517-8
  43. Davani, S., Marandin, A., Mersin, N., Royer, B., Kantelip, B., Herve, P., Etievent, J. P. and J. P. Kantelip (2003), Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model, Circulation, 108, 11253-11258
  44. Kobayashi, T., Harnano, K., Li, T. S., Katoh, T., Kobayashi, S., Matsuzaki, M. and K. Esato (2000), Enhancement of angiogenesis by the implantation of self bone marrow cells in a rat ischemic heart model, J. Surg. Res. 89, 189-195 https://doi.org/10.1006/jsre.2000.5828
  45. Schmidt, M., Zickler, P., Hoffmann, G., Haas, S., Wissler, M., Muessig, A., Tisdale, J. F., Kuramoto, K., Andrews, R. G., Wu, T., Kiem, H. P., Dunbar, C. E. and C. Von Kalle (2002), Polyclonal long-term repopulating stem cell clones in a primate model, Blood, 100, 2737-2743 https://doi.org/10.1182/blood-2002-02-0407
  46. Kehat, I., Kenyagin-Karsenti, D., Snir, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J. and L. Gepstein (2001), Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes, J. Clin. Invest. 108, 407-414 https://doi.org/10.1172/JCI200112131
  47. Munnnery, C., Ward, D., van den Brink, C. E., Bird, S. D., Doevendans, P. A., Opthof, T., Brutel de la Riviere, A., Tertoolen, L., van der Heyden, M. and M. Pera (2002), Cardiomyocyte differentiation of mouse and human embryonic stem cells. J. Anat. 200, 233-242 https://doi.org/10.1046/j.1469-7580.2002.00031.x
  48. Xu, R. H., Chen, X., Li, D. S., Li, R., Addicks, G. C., Glennon, C., Zwaka, T. P. and J. A. Thomson (2002), BMP4 initiates human embryonic stem cell differentiation to trophoblast, Nature Biotechnol. 20, 1261-1264 https://doi.org/10.1038/nbt761
  49. Xu, C., Police, S., Rao, N. and M. K. Carpenter (2002), Characterization and enrichment of cardiomyoctes derived from human embryonic stem cells, Circ. Res. 91, 501-508 https://doi.org/10.1161/01.RES.0000035254.80718.91
  50. Levenberg, S., Golub, J. S., Amit, M., Itskovitz-Eldor, J. and R. Langer (2002), Endothelial cells derived from human embryonic stem cells, Proc. Natl. Acad. Sci. USA, 99, 4391-4396
  51. Drukker, M. (2002), Characterization of the expression of MHC proteins in human embryonic stem cells, Proc. Natl. Acad. Sci. USA, 99, 9864-9869
  52. Draper, J. S. (2002), Surface antigens of human embryonic stem cells: changes upon differentiation in culture, J. Anat., 200, 249-258 https://doi.org/10.1046/j.1469-7580.2002.00030.x
  53. Rubinstein, P. (2001), HLA matching for bone marrow transplantation ? how much is enough? N. Engl. J. Med. 345, 1842-1844 https://doi.org/10.1056/NEJM200112203452511
  54. Fandrich, F. (2002), Preimplantation-stage stem cells induce longterm allogeneic graft acceptance without supplementary host conditioning, Nat. Med. 8, 171-178 https://doi.org/10.1038/nm0202-171
  55. Roopenian, D. (2002), The immunogenomics of minor histocompatibility antigens, Immunol. Rev. 190, 86-94 https://doi.org/10.1034/j.1600-065X.2002.19007.x
  56. Watkins, W. M. (2001), The ABO blood group system: historicalbackground, Transfus. Med. 11, 243-265 https://doi.org/10.1046/j.1365-3148.2001.00321.x
  57. Tada, M. (2001), Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells, Curr. BioI. 11, 1553-1558 https://doi.org/10.1016/S0960-9822(01)00459-6
  58. Serov, O. (2001), Embryonic hybrid cells: a powerful tool for studying pluripotency and reprogramming of the differentiated cell chromosomes, An. Acad. Bras. Cienc. 73, 561-568 https://doi.org/10.1590/S0001-37652001000400009
  59. Sykes, M. (2001), Mixed chimerism and ttansplant tolerance. Immunity, 14, 417-424 https://doi.org/10.1016/S1074-7613(01)00122-4
  60. Rideout, W. M. 3rd, Hochedlinger, K., Kyba, M., Daley, G. Q. and R. Jaenisch, (2002), Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy, Cell, 109, 17-27 https://doi.org/10.1016/S0092-8674(02)00681-5
  61. Bueren, J. A., Guenechea, G., Casado, J. A., Lamana, M. L. and J. C. Segovia (2003), Genetic modification of hematopoietic stem cells: recent advances in the gene therapy of inherited diseases, Arch Med. Res. 34, 589-599 https://doi.org/10.1016/j.arcmed.2003.09.004
  62. Wakitani, S., Takaoka, K., Hattori, T., Miyazawa, N., Iwanaga, T., Takeda, S., Watanabe, T. K. and A. Tanigarni (2003), Embryonic stem cells injected into the mouse knee joint form teratomas and subsequently destroy the joint, Rheumatology, 42, 162-165 https://doi.org/10.1093/rheumatology/keg024
  63. Tzukerman, M., Rosenberg, T., Ravel, Y., Reiter, I., Coleman, R. and K. Skorecki (2003), An experimental platform for studying growth and invasiveness of tumor cells within teratomas derived from human embryonic stem cells, Proc. Natl. Acad. Sci. USA, 100(23), 13507-13512
  64. Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E, Stomaiuolo, A., Cossu, G. and F. Mavilio (1998), Muscle regeneration by bone marrow-derived myogenic progenitors, Science, 279, 1528-1530 https://doi.org/10.1126/science.279.5356.1528
  65. Lagasse, E., Connors, H., Al-Dhalimy, M., Reitsma, M., Dobse, M., Osborne, L., Wang, X., Finegold M., Weissman I. L. and M. Grompe (2000), Purified hematopoietic stem cells can differentiate into hepatocytes in vivo, Nat. Med., 6, 1229-1234 https://doi.org/10.1038/81326
  66. Mezey, E., Chandross, K. J., Harta, G., Maki, R. A. and S. R. McKercher (2000), Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow, Science, 290, 1779-1782 https://doi.org/10.1126/science.290.5497.1779
  67. Brazelton, T. R., Rossi, F. M., Keshet, G. I. and H. M. Blau (2000), From marrow to brain: expression of neuronal phenotypes in adult mice, Science, 290, 1775-1779 https://doi.org/10.1126/science.290.5497.1775
  68. Gussoni, E., Soneoka, Y., Strickland, C. D., Buzney, E. A., Khan, M. K., Flint, A. F., Kunkel, L. M. and R. C. Mulligan, (1999), Dystrophin expression in the mdx mouse restored by stem cell transplantation, Nature, 401, 390-394
  69. Grant, M. B., May, W. S., Caballero, S., Brown, G. A., Guthrie, S. M., Mames, R. N., Byrne, B. J., Vaught, T., Spoerri, P. E., Peck, A. B. and E. W. Scott, (2002), Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization, Nat. Med., 8, 607-612 https://doi.org/10.1038/nm0602-607
  70. Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S. M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D. M., Leri, A. and P. Anversa (2001), Bone marrow cells regenerate infarcted myocardium, Nature, 410, 701-705 https://doi.org/10.1038/35070587
  71. Jackson, K Majka, S. M., Wang, H., Pocius, J., Hartley, C. J., Majesky, M. W., Entman, M, L., Michael, L. H., Hirschi, K K. and M. A. Goodell (2001), Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells, J Clin. Invest., 107, 1395-1402 https://doi.org/10.1172/JCI12150
  72. Fridenshtein, A. (1982), Stromal bone marrow cells and the hematopoietic microenvironment, Arkh. Patol., 44, 3-11
  73. Haynesworth, S. E. Baber, M. A. and A. I. Caplan, (1992), Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies, Bone, 13, 69-80 https://doi.org/10.1016/8756-3282(92)90363-2
  74. Gronthos, S. and P. Simmons (1996), The biology and application of human bone marrow stromal cell precursors, J. Hematother. 5, 15-23 https://doi.org/10.1089/scd.1.1996.5.15
  75. Prockop, D. (1997), Marrow stromal cells as stem cells for nonhematopoietic tissues, Science, 276, 71-74 https://doi.org/10.1126/science.276.5309.71
  76. Pittenger, M. F. Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S. and D. R. Marshak (1999), Multilineage potential of adult human mesenchymal stem cells, Science, 284, 143-147 https://doi.org/10.1126/science.284.5411.143
  77. Krause, D. S., Theise, N. D., Collector, M. I., Henegariu, O., Hwang, S., Gardner, R., Neutzel, S. and S. J., Sharkis (2001), Multi-organ, multi-lineage engraftrnent by a single bonemarrow-derived stem cell, Cell, 105, 369-377 https://doi.org/10.1016/S0092-8674(01)00328-2
  78. Petersen, B. E., Bowen, W. C. Patrene, K. D., Mars, W. M., Sullivan, A. K., Murase, N., Boggs, S. S., Greenberger, J. S. and J. P. Goff, (1999), Bone marrow as a potential source of hepatic oval cells, Science, 284, 1168-1170 https://doi.org/10.1126/science.284.5417.1168
  79. Jiang, Y., Jahagirdar, B. N., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R, Reyes, M., Lenvik, T., Lund, T., Blackstad, M., Du, J., Aldrich, S., Lisberg, A., Low, W. C., Largaespada, D. A. and C. M. Verfaillie (2002), Plutipotency of mesenchymal stem cells derived from adult marrow, Nature, 418, 41-49 https://doi.org/10.1038/nature00870
  80. Kopen, G., Prockop, D. J. and D. G.Phinney (1999), 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, 10711-10716
  81. Woodbury, D. Schwarz, E. J., Prockop, D. J. and I. B. Black (2000), Adult rat and human bone marrow stromal cells differentiate into neurons, J. Neurosci. Res., 61, 364 - 370 https://doi.org/10.1002/1097-4547(20000815)61:4<364::AID-JNR2>3.0.CO;2-C
  82. Schwartz, R. E., Reyes, M., Koodie, L., Jiang, Y., Blackstad, M., Lund, T., Lenvik, T., Johnson, S., Hu, W. S. and C. M. Verfaillie, (2002), Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells, J. Clin. Invest., 109, 1291-1302 https://doi.org/10.1172/JCI0215182
  83. Reyes, M., Dudek, A., Jahagirdar, B., Koodie, L., Marker, P. H. and C. M. Verfaillie (2002), Origin of endothelial progenitors in human post-natal bone marrow, J. Clin. Invest., 109, 337-346 https://doi.org/10.1172/JCI0214327
  84. Bjornson, C., Rietze, R. L., Reynolds, B. A., Magli, M. C. and A. L. Vescovi (1999), Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo, Science, 283, 354-357
  85. Shih, C. C., Weng, Y., Mamelak, A., LeBon, T., Hu, M. C. and S. J. Forman (2001), Identification of a candidate human neurohematopoietic stem-cell population, Blood, 98, 2412-2422 https://doi.org/10.1182/blood.V98.8.2412
  86. Clarke, D. L., Johansson, C. B., Wilbertz, J., Veress, B., Nilsson, E, Karlstrom, H., Lendahl, U. and J. Frisen (2000), Generalized potential of adult neural stem cells, Science 288, 1660-1663 https://doi.org/10.1126/science.288.5471.1660
  87. Jackson, K., Mi, T. and M. A. Goodell (1999), Hematopoietic potential of stem cells isolated from mutine skeletal muscle, Proc. Natl. Acad. Sci. USA, 96, 14482-14486
  88. McKinney-Freeman, S. L., Jackson, K. A., Camargo, F. D., Ferrari, G., Mavilio, F. and M. A. Goodell (2002), Muscle-derived hematopoietic stem cells are hematopoietic in origin, Proc. Natl. Acad. Sci. USA, 99, 1341-1346
  89. Kawada, H. and M. Ogawa (2001), Bone marrow origin of hematopoietic progenitors and stem cells in murine muscle, Blood, 98, 2008-2013 https://doi.org/10.1182/blood.V98.7.2008
  90. Yang, L., Li, S., Hatch, H., Ahrens, K., Cornelius, J. G., Petersen, B. E. and A. B. Peck (2002), In vitro trans-differentiationof adult hepatic stem cells into pancreatic endocrine hormone-producing cells. Proc. Nat!. Acad. Sci. USA, 99, 8078-8083
  91. Toma, J. G., Akhavan, M., Fernandes, K. J., Barnabe-Hcider, F., Sadikot, A., Kaplan, D. R. and F. D. Miller (2001), Isolation of multipotent adult stem cells from the dennis of mammalian skin, Nat. Cell Biol., 3, 778-784 https://doi.org/10.1038/ncb0901-778
  92. Shen, C. N., Slack, J. M. and D. Tosh (2000), Molecular basis of transdifferentiation of pancreas to liver, Nat. Cell Biol., 2, 879-887 https://doi.org/10.1038/35046522
  93. Larochelle, A., Vormoor, J., Hanenberg, H., Wang, J. C., Bhatia, M., Lapidot, T., Moritz, T., Murdoch, B., Xiao, X. L., Kato, I., Williams, D. A. and J. E. Dick (1996), Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy, Nat. Med., 2, 1329-1337 https://doi.org/10.1038/nm1296-1329
  94. Horwitz, E. M., Prockop, D. J., Fitzpatrick, L. A., Koo, W. W., Gordon, P. L., Neel, M., Sussman, M., Orchard, P., Marx, J. C., Pyeritz, R. E. and M. K. Brenner, (1999), Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta, Nat. Med., 5, 309-313 https://doi.org/10.1038/6529
  95. McKay, R. (1997), Stem cells in the central nervous system, Science, 276, 66-71 https://doi.org/10.1126/science.276.5309.66
  96. Gage, F. H. (2000), Mammalian neural stem cells, Science 287, 1433-1438 https://doi.org/10.1126/science.287.5457.1433
  97. Taupin, P. (2002), Adult neurogenesis and neural stem cells of the central nervous system in mammals, J. Neurosci. Res., 69, 745-749 https://doi.org/10.1002/jnr.10378
  98. Shih, C. C., Weng. Y., Mamelak, A., Lebon, T., Hu, M. C. and S. J. Forman (2001), Identification of a candidate human neurohematopoietic stem-cell population, Blood, 98, 2412-2422 https://doi.org/10.1182/blood.V98.8.2412
  99. Erices, A., Conger, P., and J. J. Minguell (2000), Mesenchymal progenitor cells in human umbilical cord blood, Brit. J. Haemato. 109, 235-242 https://doi.org/10.1046/j.1365-2141.2000.01986.x
  100. Mollah, Z. U., Aiba, S., Manome, H., Yoshino, Y. and Tagarni, H. (2002), Cord blood CD34- cells differentiate into dermal dendritic cells in co-culture with cutaneous fibroblasts or stromal cells, J. Invest. Dermatol. 118, 450-460 https://doi.org/10.1046/j.0022-202x.2001.01692.x
  101. Sanchez-Ramos, J. R. (2002), Neural cells derived from adult bone marrow and wnbilical cord blood, J. Neurosci. Res. 69, 880-893 https://doi.org/10.1002/jnr.10337
  102. Murphy, J. M., Fink, D. J., Hunziker, E. B. and F. P. Barry (2003), Stem cell therapy in a caprine model of osteoarthritis, Arthritis Rheum. 48, 3464-3474 https://doi.org/10.1002/art.11365
  103. Barry, F. P. (2003), Biology and clinical applications of mesenchymal stem cells, Birth Defects Res. Part C Embryo Today, 69, 250-256 https://doi.org/10.1002/bdrc.10021