Abstract
This report reviews three categories of precursor cells present within adults. The first category of precursor cell, the epiblast‐like stem cell, has the potential of forming cells from all three embryonic germ layer lineages, e.g., ectoderm, mesoderm, and endoderm. The second category of precursor cell, the germ layer lineage stem cell, consists of three separate cells. Each of the three cells is committed to form cells limited to a specific embryonic germ layer lineage. Thus the second category consists of germ layer lineage ectodermal stem cells, germ layer lineage mesodermal stem cells, and germ layer lineage endodermal stem cells. The third category of precursor cells, progenitor cells, contains a multitude of cells. These cells are committed to form specific cell and tissue types and are the immediate precursors to the differentiated cells and tissues of the adult. The three categories of precursor cells can be readily isolated from adult tissues. They can be distinguished from each other based on their size, growth in cell culture, expressed genes, cell surface markers, and potential for differentiation. This report also discusses new findings. These findings include the karyotypic analysis of germ layer lineage stem cells; the appearance of dopaminergic neurons after implantation of naive adult pluripotent stem cells into a 6‐hydroxydopamine‐lesioned Parkinson's model; and the use of adult stem cells as transport mechanisms for exogenous genetic material. We conclude by discussing the potential roles of adult‐derived precursor cells as building blocks for tissue repair and as delivery vehicles for molecular medicine.
Keywords: adult, stem cells, mammals, humans, Parkinson's Disease, molecular medicine
References
- 1. Young HE. Existence of reserve quiescent stem cells in adults, from amphibians to humans. Curr Top Microbiol Immunol. 2004; 280: 71–109. [DOI] [PubMed] [Google Scholar]
- 2. Young HE, Black AC Jr. Adult stem cells. Anat Rec A Discov Mol Cell Evol Biol. 2004; 276A: 75–102. [DOI] [PubMed] [Google Scholar]
- 3. Young HE, Black AC Jr. Differentiation potential of adult stem cells In: Contemporary Endocrinology: Stem Cells in Endocrinology. Lester L.B. ed. The Humana Press Inc; Totowa NJ . 2005; 67–92. [Google Scholar]
- 4. Young HE, Duplaa C, Romero‐Ramos M, Chesselet MF, Vourc'h P, Yost MJ, Ericson K, Terracio L, Asahara T, Masuda H, Tamura‐Ninomiya S, Detmer K, Bray RA, Steele TA, Hixson D, El‐Kalay M, Tobin BW, Russ RD, Horst MN, Floyd JA, Henson NL, Hawkins KC, Groom J, Parikh A, Blake L, Bland LJ, Thompson AJ, Kirincich A, Moreau C, Hudson J, Bowyer FP III, Lin TJ, Black AC Jr. Adult reserve stem cells and their potential for tissue engineering. Cell Biochem Biophys. 2004a; 40: 1–80. [DOI] [PubMed] [Google Scholar]
- 5. Young HE, Duplaa C, Yost MJ, Henson NL, Floyd JA, Detmer K, Thompson AJ, Powell SW, Gamblin TC, Kizziah K, Holland BH, Boev A, Van De Water JM, Godbee DC, Jackson S, Rimando M, Edwards CR, Wu E, Cawley C, Edwards PD, Macgregor A, Bozof R, Thompson TM, Petro GJ Jr, Shelton HM, McCampbell BL, Mills JC, Flynt FL, Steele TA, Kearney M, Kirincich‐Greathead A, Hardy W, Young PR, Amin AV, Williams RS, Horton MM, McGuinn S, Hawkins KC, Ericson K, Terracio L, Moreau C, Hixson D, Tobin BW, Hudson J, Bowyer FP III, Black AC Jr. Clonogenic analysis reveals reserve stem cells in postnatal mammals. II. Pluripotent epiblastic‐like stem cells. Anat Rec. 2004; 277A: 178–203. [DOI] [PubMed] [Google Scholar]
- 6. Young HE, Black AC Jr. Adult‐derived stem cells. Minerva Biotechnologica. (In press). 2005.
- 7. Henson NL, Heaton ML, Holland BH, Hawkins KC, Rollings B, Eanes E, Bozof R, Powell S, Grau R, Fortney J, Peebles B, Kumar D, Yoon JI, Godby K, Floyd JA, Bowyer FP, Black AC Jr, Young HE. Karyotypic analysis of adult pluripotent stem cells. Histol Histopath (In press). 2005. [DOI] [PubMed]
- 8. Young HE. Wright RP, Mancini ML, Lucas PA, Reagan CR, Black AC Jr. Bioactive factors affect proliferation and phenotypic expression in progenitor and pluripotent stem cells. Wound Rep Reg. 1998; 6: 66–75. [DOI] [PubMed] [Google Scholar]
- 9. Thomson JA, Itskovitz‐Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145–7. [DOI] [PubMed] [Google Scholar]
- 10. Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, Huggins GR, Gearhart JD. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA. 1998; 95: 13726–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Hayflick L, Moorehead P. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961; 25: 585–621. [DOI] [PubMed] [Google Scholar]
- 12. Rohme D. Evidence for a relationship between longevity of mammalian species and life spans of normal fibroblasts in vitro and erythrocytes in vivo . Proc Natl Acad Sci USA. 1981; 78: 5009–13. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM. Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle and brain. Exp Hematol. 2002; 30: 896–904. [DOI] [PubMed] [Google Scholar]
- 14. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz‐Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41–9. [DOI] [PubMed] [Google Scholar]
- 15. Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 2002; 109: 337–46. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte‐like cells. J Clin Invest. 2002; 109: 1291–302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Woodbury D, Schwartz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000; 61: 364–70. [DOI] [PubMed] [Google Scholar]
- 18. Li H, Liu H, Heller S. Pluripotent stem cells from the adult mouse inner ear. Nat Med. 2003; 9: 1293–9. [DOI] [PubMed] [Google Scholar]
- 19. Zhao Y, Glesne D, Huberman E. A human peripheral blood monocyte‐derived subset acts as pluripotent stem cells. Proc Natl Acad Sci USA 2003; 100: 2426–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. D'Ippolito G, Diabira S, Howard GA, Menei P, Roos BA, Schiller PC. Marrow‐isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci. 2004; 117: 2971–81. [DOI] [PubMed] [Google Scholar]
- 21. Young HE, Steele T, Bray RA, Detmer K, Blake LW, Lucas PA, Black AC Jr. Human pluripotent and progenitor cells display cell surface cluster differentiation markers CD10, CD13, CD56, and MHC Class‐I. Proc Soc Exp Biol Med. 1999; 221: 63–71. [DOI] [PubMed] [Google Scholar]
- 22. Young HE, Duplaa C, Young TM, Floyd JA, Reeves ML, Davis KH, Mancini GJ, Eaton ME, Hill JD, Thomas K, Austin T, Edwards C, Cuzzourt J, Parikh A, Groom J, Hudson J, Black AC Jr. Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells. Anat Rec. 2001; 263: 350–60. [DOI] [PubMed] [Google Scholar]
- 23. Young HE, Steele T, Bray RA, Hudson J, Floyd JA, Hawkins K, Thomas K, Austin T, Edwards C, Cuzzourt J, Duenzl M, Lucas PA, Black AC Jr. Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec. 2001; 264: 51–62. [DOI] [PubMed] [Google Scholar]
- 24. Romero‐Ramos M, Vourc'h P, Young HE, Lucas PA, Wu Y, Chivatakarn O, Zaman R, Dunkelman N, El‐Kalay MA, Chesselet MF. Neuronal differentiation of stem cells isolated from adult muscle. J Neurosci Res. 2002; 69: 894–907. [DOI] [PubMed] [Google Scholar]
- 25. Vourc'h P, Romero‐Ramos M, Chivatakarn O, Young HE, Lucas PA, El‐Kalay M, Chesselet MF. Isolation and characterization with neurogenic potential from adult skeletal muscle. Biochem Biophys Res Commun. 2004; 317: 893–901. [DOI] [PubMed] [Google Scholar]
- 26. Vourc'h P, Lacar B, Mignon L, Lucas PA, Young HE, Chesselet MF. Effect of neurturin on mulitpotent cells isolated from the adult skeletal muscle. Biochem Biophys Res Commun. 2005; 332: 215–23. [DOI] [PubMed] [Google Scholar]
- 27. Vourc'h P, Mignon L, Lucas PA, Young HE, Chesselet MF. Cells isolated from adult skeletal muscle express markers of differentiated neurons after transplantation into the adult hippocampus, (submitted). 2005.
- 28. Mignon L, Vourc'h P, Romero‐Ramos M, Osztermann P, Young HE, Lucas PA, Chesselet MF. Transplantation of multipotent cells extracted from adult skeletal muscles into the adult subventricular zone. J Cell Neurol (In press). 2005. [DOI] [PubMed]
- 29. Braun KM, Watt FM. Epidermal label‐retaining cells: background and recent applications. J Investig Dermatol Symp Proc. 2004; 9: 196–201. [DOI] [PubMed] [Google Scholar]
- 30. Ashjian PH, Elbarbary AS, Edmonds B, DeUgarte D, Zhu M, Zuk PA, Lorenz HP, Benhaim P, Hedrick MH. In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. Plast Reconstr Surg. 2003; 111: 1922–31. [DOI] [PubMed] [Google Scholar]
- 31. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71–4. [DOI] [PubMed] [Google Scholar]
- 32. Trosko JE. Chang CC. Wilson MR, Upham B, Hayashi T. Wade M. Gap junctions and the regulation of cellular functions of stem cells during development and differentiation. Methods 2000; 20: 245–64. [DOI] [PubMed] [Google Scholar]
- 33. McKinney‐Freeman SL, Jackson KA, Camargo FD, Ferrari G, Mavilio F, Goodell MA. Muscle‐derived hematopoietic stem cells are hematopoietic in origin. Proc Natl Acad Sci USA. 2002; 99: 1341–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002; 13: 4279–95. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Trosko JE, Chang CC. Isolation and characterization of normal adult human epithelial pluripotent stem cells. Oncol Res. 2003; 13: 353–7. [DOI] [PubMed] [Google Scholar]
- 36. Kotobuki N, Hirose M, Takakura Y, Ohgushi H. Cultured autologous human cells for hard tissue regeneration: preparation and characterization of mesenchymal stem cells from bone marrow. Artif Organs 2004; 28: 33–39. [DOI] [PubMed] [Google Scholar]
- 37. Kacsoh B. Endocrine physiology. New York : McGraw‐Hill, 2000. [Google Scholar]
- 38. Petersen BE. Hepatic “stem” cells: coming full circle. Blood Cells Mol Dis. 2001; 27: 590–600. [DOI] [PubMed] [Google Scholar]
- 39. Kishimoto T, Kikutani H, Borne, AEG Krvd , Goyert SM, Mason D, Miyasaka M, Moretta L, Okumura K, Shaw S, Springer T, Sugamura K, Zola H. Leucocyte Typing VI, White Cell differentiation antigens. New York , Garland Publishing, 1998. [Google Scholar]
- 40. Young HE, Morrison DC, Martin JD, Lucas PA. Cryopreservation of embryonic chick myogenic lineagecommitted stem cells. J Tiss Cult Meth. 1991; 13: 275–84. [Google Scholar]
- 41. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–7. [DOI] [PubMed] [Google Scholar]
- 42. Mauro A. Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol. 1961; 9: 493–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43. Cruess RL. The Musculoskeletal System: Embryology, Biochemistry, and Physiology. New York , Churchill Livingston, 1982; pp. 1–33, 109–169, 255–287. [Google Scholar]
- 44. Grounds MD, Garrett KL, Lai MC, Wright WE, Beilharz MW. Identification of muscle precursor cells in vivo by use of MyoD1 and myogenin probes. Cell Tiss Res. 1992; 267: 99–104. [DOI] [PubMed] [Google Scholar]
- 45. Campion DR. The muscle satellite cell: a review. Int Rev Cytol. 1984; 87: 225–51. [DOI] [PubMed] [Google Scholar]
- 46. Owen M. Marrow stromal cells. J Cell Sci Suppl. 1988; 10: 63–76. [DOI] [PubMed] [Google Scholar]
- 47. Beresford JN. Osteogenic stem cells and the stromal system of bone and marrow. Clin Orthop. 1989; 240: 270–80. [PubMed] [Google Scholar]
- 48. Ailhaud G, Grimaldi P, Negrel R. Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr. 1992; 12: 207–33. [DOI] [PubMed] [Google Scholar]
- 49. Vierck JL, McNamara JP, Dodson MV. Proliferation and differentiation of progeny of ovine unilocular fat cells (adipofibroblasts). In Vitro Cell Dev Biol Anim. 1996; 32: 564–72. [DOI] [PubMed] [Google Scholar]
- 50. Caplan AI, Elyaderani M, Mochizuki Y, Wakitani S, Goldberg V. Principles of cartilage repair and regeneration. Clin Orthop Rel Res. 1997; 342: 254–69. [PubMed] [Google Scholar]
- 51. McGuire WP. High‐dose chemotherapy and autologous bone marrow or stem cell reconstitution for solid tumors. Curr Probl Cancer 1998; 22: 135–177. [DOI] [PubMed] [Google Scholar]
- 52. Palis J, Segel GB. Developmental biology of erythropoiesis. Blood Rev. 1998; 12: 106–14. [DOI] [PubMed] [Google Scholar]
- 53. Ratajczak MZ, Pletcher CH, Marlicz W, Machlinski B, Moore J, Wasik M, Ratajczak J, Gewirtz AM. CD34+, kit+, rhodamine 123 (low) phenotype identifies a marrow cell population highly enriched for human hematopoietic stem cells. Leukemia 1998; 12: 942–950. [DOI] [PubMed] [Google Scholar]
- 54. Caterson EJ, Nesti LJ, Danielson KG, Tuan RS. Human marrow‐derived mesenchymal progenitor cells: isolation, culture expansion, and analysis of differentiation. Mol Biotechnol. 2002; 20: 245–56. [DOI] [PubMed] [Google Scholar]
- 55. Majka SM, Jackson KA, Kienstra KA, Majesky MW, Goodell MA, Hirschi KK. Distinct progenitor populations in skeletal muscle are bone marrow derived and exhibit different cell fates during vascular regeneration. J Clin Invest. 2003; 111: 71–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56. Hattori H, Sato M, Masuoka K, Ishihara M, Kikuchi T, Matsui T, Takase B, Ishizuka T, Kikuchi M, Fujikawa K, Ishihara M. Osteogenic potential of human adipose tissue‐derived stromal cells as an alternative stem cell source. Cells Tissues Organs 2004; 178: 2–12. [DOI] [PubMed] [Google Scholar]
- 57. Hsieh J, Aimone JB, Kaspar BK, Kuwabara T, Nakashima K, Gage FH. IGF‐I instructs multipotent adult neural progenitor cells to become oligodendrocytes. J Cell Biol. 2004; 164: 111–22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58. Markakis EA, Palmer TD, Randolph‐Moore L, Rakic P, Gage FH. Novel neuronal phenotypes from neural progenitor cells. J Neurosci. 2004; 24: 2886–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 59. Merkle FT, Tramontin AD, Garcia‐Verdugo JM, Alvarez‐Buylla A. Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci USA. 2004; 101: 17528–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60. Young HE. Stem cells and tissue engineering In: Huard J, Fu FH. eds., Gene Therapy in Orthopaedic and Sports Medicine. Chap. 9. Springer‐Verlag New York Inc; 2000; 143–173. [Google Scholar]
- 61. Lazic SE. Barker RA. The future of cell‐based transplantation therapies for neurodegenerative disorders. J Hematother Stem Cell Res. 2003; 12: 635–42. [DOI] [PubMed] [Google Scholar]
- 62. Parati EA, Bez A, Ponti D, Sala S, Pozzi S, Pagano SF. Neural stem cells. Biological features and therapeutic potential in Parkinson's disease. J Neurosurg Sci. 2003; 47: 8–17. [PubMed] [Google Scholar]
- 63. Hynes M, Rosenthal A. Embryonic stem cells go dopaminergic. Neuron 2000. 28: 11–4. [DOI] [PubMed] [Google Scholar]
- 64. Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ. Tremor in Parkinson's disease and serotonergic dysfunction: an (11)C‐WAY 100635 PET study. Neurology 2003; 60: 601–5. [DOI] [PubMed] [Google Scholar]
- 65. Gerlach M, Riederer P. Animal models of Parkinson's disease: an empirical comparison with the phenomenology of the disease in man. J Neural Transm. 1996; 103: 987–1041. [DOI] [PubMed] [Google Scholar]
- 66. Thompson TL, Moss RL. In vivo stimulated dopamine release in the nucleus accumbens: modulation by the prefrontal cortex. Brain Res. 1995; 686: 93–8. [DOI] [PubMed] [Google Scholar]
- 67. Lee CS, Cenci MA, Schulzer M, Bjorklund A. Embryonic ventral mesencephalic grafts improve levodopa‐induced dyskinesia in a rat model of Parkinson's disease. Brain 2000; 123: 1365–79. [DOI] [PubMed] [Google Scholar]
- 68. Lindvall O. Stem cells for cell therapy in Parkinson's disease. Pharmacol Res. 2003; 47: 279–87. [DOI] [PubMed] [Google Scholar]
- 69. Lewis DA, Melchitzky DS, Haycock JW. Four isoforms of tyrosine hydroxylase are expressed in human brain. Neuroscience 1993; 54: 477–92. [DOI] [PubMed] [Google Scholar]
- 70. Miyazono M, Nowell PC, Finan JL, Lee VM, Trojanowski JQ. Long‐term integration and neuronal differentiation of human embryonal carcinoma cells (NTera‐2) transplanted into the caudoputamen of nude mice. J Comp Neurol. 1996; 376: 603–13. [DOI] [PubMed] [Google Scholar]
- 71. Bjorklund LM, Sanchez‐Pernaute R, Chung S, Anderrsson T, Chen IY, McNaught KS, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Nat Acad Sci USA. 2002; 99: 2344–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 72. Deascon T, Dinsmor J, Costantini LC, Ratliff J, Isacson O. Blastula‐stage cells can differentiate into dopaminergic and serotonergic neurons after transplantation. Exp Neurol 1998; 149: 28–41. [DOI] [PubMed] [Google Scholar]
- 73. Doering LC, Snyder EY. Choliergic expression by a neural stem cell line grafted to the adult medical septum/diagonal band complex. J Neurosci Res. 2000; 61: 597–604. [DOI] [PubMed] [Google Scholar]
- 74. Yang M, Stull ND, Berk MA, Snyder EY, Iacovitti L. Neural stem cell spontaneously express dopaminergic traits after transplantation into the intact or 6‐hydroxydopamine‐lesioned rat. Exp Neurol. 2002; 177: 50–60. [DOI] [PubMed] [Google Scholar]
- 75. Anderson DJ. Stem cells and pattern formation in the nervous system: the possible versus the actual. Neuron 2001; 30: 19–35. [DOI] [PubMed] [Google Scholar]
- 76. Temple S, Alvarez‐Buylla A. Stem cells in the adult mammalian central nervous system. Curr Opin Neurobiol. 1999; 9: 135–41. [DOI] [PubMed] [Google Scholar]
- 77. Gritti A, Parati EA, Cova L, Frolichsthal P, Galli R, Wanke E, Faravelli L, Morassutti DJ, Roisen F, Nickel DD, Vescovi AL. Multipotential stem cells from adult mouse brain proliferate and self‐renew in response to basic fibroblast growth factor. J Neurosci. 1996; 16: 1091–100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 78. McKay R. Stem cells in the central nervous system. Science 1997; 276: 66–71. [DOI] [PubMed] [Google Scholar]
- 79. Carpenter MK, Cui X, Hu ZY, Jackson J, Sherman S, Seiger A, Wahlberg LU. In vitro expansion of a multipotent population of human neural progenitor cells. Exp Neurol. 1999; 158: 265–78. [DOI] [PubMed] [Google Scholar]
- 80. Svendsen CN, Caldwell MA, Ostenfeld T. Human neural stem cells: isolation, expansion and transplantation. Brain Pathol. 1999; 9: 499–513. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 81. Gage FH. Mammalian neural stem cells. Science 2000; 287: 1433–8. [DOI] [PubMed] [Google Scholar]
- 82. Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, Weissman IL. Direct isolation of human central nervous system stem cells. Proc Nat Acad Sci USA. 2000; 97: 14720–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 83. Song H, Stevens CF, Gage FH. Astroglia induce neurogenesis from adult neural stem cells. Nature 2002; 417: 39–44. [DOI] [PubMed] [Google Scholar]
- 84. Storch A, Schwarz J. Neural stem cells and neurodegeneration. Curr Opin Investig Drugs 2002; 3: 774–81. [PubMed] [Google Scholar]
- 85. Johe KK, Hazal TG, Muller T, Dugich‐Djordjevic MM, McKay RD. Single factors direct the differentiation of stem cells from fetal and adult nervous system. Genes Dev. 1996; 10: 3129–40. [DOI] [PubMed] [Google Scholar]
- 86. Mayer‐Proschel M, Kalyani AJ, Mujtaba T, Rao MS. Isolation of lineage‐restricted neuronal precursors from multipotent neuroepithelial stem cells. Neuron 1997; 19: 773–85. [DOI] [PubMed] [Google Scholar]
- 87. Potter ED, Ling Z, Carvey PM. Cytokine‐induced conversion of mesencephalic‐derived progenitor cells into dopamine neurons. Cell Tissue Res. 1999; 296: 235–46. [DOI] [PubMed] [Google Scholar]
- 88. Ling ZD, Potter ED, Lipton JW, Carvey PM. Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines. Exp Neurol. 1998; 149: 411–23. [DOI] [PubMed] [Google Scholar]
- 89. Storch A, Paul G, Csete M, Boehm BO, Carvey PM, Kupsch A, Schwarz J. Long‐term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells. Exp Neurol. 2001; 170: 317–25. [DOI] [PubMed] [Google Scholar]
- 90. Li Y, Chen J., Wang L, Zhang L, Lu M, Chopp M. Intracerebral transplantation of bone marrow stromal cells in a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine model of Parkinson's disease. Neurosci Lett. 2001; 316: 67–70. [DOI] [PubMed] [Google Scholar]
- 91. Ying Q, Nichols J, Evans EP, Smith AG. Changing potency by spontaneous fusion. Nature 2002; 416: 545–8. [DOI] [PubMed] [Google Scholar]
- 92. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 2002; 416: 542–5. [DOI] [PubMed] [Google Scholar]
- 93. Vogel G. Stem cell policy. Can adult stem cells suffice Science 2001; 292: 1820–2. [DOI] [PubMed] [Google Scholar]