The potential of marrow stromal cells in stem cell therapy

1. Morrison SJ, Shah NM, Anderson DJ . Regulatory mechanisms in stem cell biology. Cell 1997;88:287–98.

   Article  CAS  PubMed  Google Scholar 

2. Vescovi AL, Parati EA, Gritti A, Poulin P, Ferrario M, Wanke E, et al. Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. Exp Neurol 1999;156:71–83.

   Article  CAS  PubMed  Google Scholar 

3. Evans MJ, Kaufman MH . Establishment in culture of pluripotential cells from mouse embryos. Nature 1981;292:154–6.

   Article  CAS  PubMed  Google Scholar 

4. Kopen GC, Prockop DJ, Phinney DG . Marrow stromal cells migrate throughout the forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 1999;96:10711–6.

   Article  CAS  PubMed  PubMed Central  Google Scholar 

5. Morrison SJ, Uchida N, Weissman IL . The biology of haematopoietic stem cells. Annu Rev Cell Dev Biol 1995;11:35–71.

   Article  CAS  PubMed  Google Scholar 

6. Dexter TM, Allen TD, Lajtha LG . Conditions controlling the proliferation of haematopoietic cells in vitro. J Cell Physiol 1977;91:335–44.

   Article  CAS  PubMed  Google Scholar 

7. Negishi Y, Kudo A, Obinata A, Kawashima K, Hirano H, Yanai N, et al. Multipotency of a bone marrow stromal cell line, TBR31-2, established from ts-SV40 T antigen gene transgenic mice. Biochem Biophys Res Commun 2000;268:450–5.

   Article  CAS  PubMed  Google Scholar 

8. Kuznetsov SA, Friedenstein AJ, Robey PG . Factors required for bone marrow stromal fibroblast colony formation in vitro. Br J Haematol 1997;97:561–70.

   Article  CAS  PubMed  Google Scholar 

9. Caplan AI . Mesenchymal stem cells. J Orthop Res 1991;9:641–50.

   Article  CAS  PubMed  Google Scholar 

10. Pereira RF, O'Hara MD, Laptev AV, Haiford KW, Pollard MD, Class R, et al. Marrow stromal cells as a source of progenitor cells for nonhaematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc Natl Acad Sci USA 1998;95:1142–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

11. Prockop DJ . Marrow stromal cells as stem cells for nonhaematopoietic tissues. Science 1997;276:171–4.

    Article  Google Scholar 

12. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998;279:1528–30.

    Article  CAS  PubMed  Google Scholar 

13. Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL . Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSCs) and stromal cells. J Cell Physiol 1998;176:57–66.

    Article  CAS  PubMed  Google Scholar 

14. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–7.

    Article  CAS  PubMed  Google Scholar 

15. Azizi SA, Stokes D, Augelli BJ, DiGirolamo C, Prockop DJ . Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats: similarities to astrocyte grafts. Proc Natl Acad Sci USA 1998;95:3908–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

16. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, et al. Bone marrow as a source of hepatic oval cells. Science 1999;284:1168–70.

    Article  CAS  PubMed  Google Scholar 

17. Sanchez-Ramos JR, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, et al. Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 2000;164:247–56.

    Article  CAS  PubMed  Google Scholar 

18. Gronthos S, Graves SE, Ohta S, Simmons PJ . The STRO-1 + fraction of adult human bone marrow contains the osteogenic precursors. Blood 1994;84:4164–73.

    CAS  PubMed  Google Scholar 

19. Phinney DG, Kopen G, Isaccson RL, Prockop DJ . Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation. J Cell Biochem 1999;72:570–85.

    Article  CAS  PubMed  Google Scholar 

20. Keating A, Powell J, Takahashi M, Singer JW . The generation of human long-term marrow cultures from marrow depleted of Ia (HLA-DR) positive cells. Blood 1984;64:1159–62.

    CAS  PubMed  Google Scholar 

21. Otsuka T, Humphries RK, Hogge DE, Eaves AC, Eaves CJ . Continuous activation of primitive haematopoietic cells in long-term human marrow cultures containing irradiated tumour cells. J Cell Physiol 1991;148:370–9.

    Article  CAS  PubMed  Google Scholar 

22. Gordon MY, Lewis JL, Grand FH, Marley SB, Glodman JM . Phenotype and progeny of primitive adherent human haematopoietic progenitors. Leukemia 1996;10:1347–53.

    CAS  PubMed  Google Scholar 

23. Woodbury D, Schwartz EJ, Prockop DJ, Black IB . Adult rat and human bone marrow stromal cells differentiate into neurones. J Neurosci Res 2000;61:364–70.

    Article  CAS  PubMed  Google Scholar 

24. Reh TA, Kljavin IJ . Age of differentiation determines rat retinal germinal cell phenotype: induction of differentiation by dissociation. J Neurosci 1989;9:4179–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

25. 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.

    Article  CAS  PubMed  Google Scholar 

26. Davis AA, Matzuk MM, Reh TA . Activin A promotes progenitor differentiation into photoreceptors in rodent retina. Mol Cell Neurosci 2000;15:11–21.

    Article  CAS  PubMed  Google Scholar 

27. Rubio FJ, Bueno C, Villa A, Navarro B, Martinez-Serrano A . Genetically perpetuated human neural stem cells engraft and differentiate into the adult mammalian brain. Mol Cell Neurosci 2000;16:1–13.

    Article  CAS  PubMed  Google Scholar 

28. Bjornson CRR, Rietze RL, Reynolds BA, Magli C, Vescovi AL . Turning brain into blood: a haematopoietic fate adopted by adult neural stem cells in vivo. Science 1999;283:534–7.

    Article  CAS  PubMed  Google Scholar 

29. Friedenstein AJ, Gorskaja JF, Kulagina NN . Fibroblast precursors in normal and irradiated mouse haematopoietic organs. Exp Hematol 1976;4:267–74.

    CAS  PubMed  Google Scholar 

30. Keating A, Singer JW, Killen PD, Striker GE, Salo AC, Sanders J, et al. Donor origin of the in vitro haematopoietic microenvironment after marrow transplantation in man. Nature 1982;298:280–3.

    Article  CAS  PubMed  Google Scholar 

31. Zuckerman KS, Wicha MS . Extracellular matrix production by the adherent cells of long-term murine bone marrow cultures. Blood 1983;61:540–7.

    CAS  PubMed  Google Scholar 

32. Lim B, Izaguirre CA, Aye MT, Heubsch L, Drouin J, Richardson C, et al. Characterisation of reticulofibroblastoid colonies (CFU-RF) derived from bone marrow and long-term marrow culture monolayers. J Cell Physiol 1986;127:45–54.

    Article  CAS  PubMed  Google Scholar 

33. Perkins S, Fleischman RA . The in vitro hematopoietic microenvironment: origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice. J Clin Invest 1988;81:1072–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

34. Perkins S, Fleischman RA . The stromal cell progeny of murine bone marrow CFU-F are clonal endothelial-like cells that express collagen type IV and laminin. Blood 1990;75:620–5.

    CAS  PubMed  Google Scholar 

35. Charbord P, Gown AM, Keating A, Singer JW . CGA-7 and HHF: two monoclonal antibodies that recognise muscle actin and react with adherent cells in human long-term bone marrow cultures. Blood 1985;66:1138–42.

    CAS  PubMed  Google Scholar 

36. Charbord P, Lerat H, Newton I, Tamayo E, Gown AM, Singer JW, et al. The cytoskeleton of stromal cells from human bone marrow cultures resembles that of cultured smooth muscle cells. Exp Haematol 1990;18:276–82.

    CAS  Google Scholar 

37. Peled A, Zipori D, Abramsky O, Ovadia H, Shezen E . Expression of a-smooth muscle actin in murine bone marrow stromal cells. Blood 1991;78:304–9.

    CAS  PubMed  Google Scholar 

38. Fei R-G, Perm PE, Wolf NS . A method to establish pure fibroblast and endothelial cell colony cultures from murine bone marrow. Exp Haematol 1990;18:953–7.

    CAS  Google Scholar 

39. Perm PE, Jiang D-Z, Fei R-G, Sitnicka E, Wolf NS . Dissecting the haematopoietic microenvironment. IX. Further characterisation of murine bone marrow stromal cells. Blood 1993;81:1205–13.

    Google Scholar 

40. Lennon JE, Micklem HS . Stromal cells in long-term murine bone marrow culture: FACS studies and origin of stromal cells in radiation chimeras. Exp Haematol 1986;14:287–92.

    CAS  Google Scholar 

41. Witte PL, Frantsve LM, Hergott M, Rahbe SM . Cytokine production and heterogeneity of primary stromal cells that support B lymphopoiesis. Eur J Immunol 1993;23:1809–17.

    Article  CAS  PubMed  Google Scholar 

42. Funk PE, Witte PL . Enrichment of primary lymphocyte-supporting stromal cells and characterisation of associated B lymphocyte progenitors. Eur J Immunol 1992;22:1305–13.

    Article  CAS  PubMed  Google Scholar 

43. Perkins S, Fleischman RA . Endothelial-like stromal cells are the exclusive source of kit ligand in the adherent layers of long-term bone marrow cultures. Blood 1992;80(Suppl 1):179a.

    Google Scholar 

44. Fleischman RA, Simpson F, Gallardo T, Jin XL, Perkins S . Isolation of endothelial-like stromal cells that express Kit ligand and support in vitro haematopoiesis. Exp Haematol 1995;23:1407–16.

    CAS  Google Scholar 

45. Abboud CN, Duerst RE, Frantz N, Ryan DH, Liesveld JL, Brennan JK . Lysis of human fibroblast colony-forming cells and endothelial cells by monoclonal antibody (6-19) and complement. Blood 1986;68:1196–200.

    CAS  PubMed  Google Scholar 

46. Simmons PJ, Torok-Strob B . Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 1991;78:55–62.

    CAS  PubMed  Google Scholar 

47. Hasthorpe S, Bogdanovski M, Rogerson J, Radley JM . Characterisation of endothelial cells in murine long-term marrow culture: implication for haematopoietic regulation. Exp Haematol 1992;20:476–81.

    CAS  Google Scholar 

48. Jacobson K, Miyake K, Kincade PW, Osmond DG . Highly restricted expression of a stromal cell determinant in mouse bone marrow in vivo. J Exp Med 1992;176:927–35.

    Article  Google Scholar 

49. Gronthos S, Simmons PJ . The growth factor requirements of STRO-1 positive human bone marrow stromal precursors under serum-deprived conditions in vitro. Blood 1995;85:929–40.

    CAS  PubMed  Google Scholar 

50. Long MW, Williams JL, Mann KG . Expression of human-related proteins in the haematopoietic microenvironment. J Clin Invest 1990;86:1387–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

51. Haynesworth SE, Baber MA, Caplan AI . Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol 1996;166:585–92.

    Article  CAS  PubMed  Google Scholar 

52. Peter SJ, Liang CR, Kim DJ, Widmer MS, Mikos AG . Osteoblastic phenotype of rat marrow stromal cells cultured in the presence of dexamethasone, β-glycerolphosphate and L-ascorbic acid. J Cell Biochem 1998;71:55–62.

    Article  CAS  PubMed  Google Scholar 

53. Lian JB, Stein GS . Concepts of osteoblast growth and differentiation: basis for modulation of bone cell development and tissue formation. Crit Rev Oral Biol Med 1992;3:269–305.

    Article  CAS  PubMed  Google Scholar 

54. Cheng SL, Yang JW, Rifas L, Zhang SF, Avioli LV . Differentiation of human bone marrow osteogenic stromal cells in vitro: induction of the osteoblast phenotype by dexamethasone. Endocrinology 1994;134:277–86.

    Article  CAS  PubMed  Google Scholar 

55. Cheng SL, Zhang SF, Avioli LV . Expression of bone matrix proteins during dexamethasone-induced mineralisation of human bone marrow stromal cells. J Cell Biochem 1996;61:182–93.

    Article  CAS  PubMed  Google Scholar 

56. Rickard D, Sullivan T, Shenker B, Leboy P, Kazhdan L . Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2. Dev Biol 1994;161:218–28.

    Article  PubMed  Google Scholar 

57. Jaiswal N, Bruder SP . The pleiotropic effects of dexamethasone on osteoblast differentiation depend on the developmental state of the responding cells. J Bone Miner Res 1996;11:S–259.

    Google Scholar 

58. Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP . Osteogenic differentiation of purified culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 1997;64:295–312.

    Article  CAS  PubMed  Google Scholar 

59. Choong PFM, Martin TJ, Ng KW . Effects of ascorbic acid, calcitriol, and retinoic acid on the differentiation of preosteoblast. J Orthop Res 1993;11:638–47.

    Article  CAS  PubMed  Google Scholar 

60. Maniatopoulos C, Sodek J, Melcher A . Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res 1988;254:317–30.

    Article  CAS  PubMed  Google Scholar 

61. Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF . Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Eng 1998;4:415–28.

    Article  CAS  PubMed  Google Scholar 

62. Yoo JU, Barthel TS, Nishimura K, Solchaga L, Caplan AI, Goldberg VM, Johnstone B . The chondrogenic potential of human bone marrow-derived mesenchymal progenitor cells. J Bone Joint Surg Am 1998;80:1745–57.

    Article  CAS  PubMed  Google Scholar 

63. Diduch DR, Jordan LC, Mierisch CM, Balian G . Marrow stromal cells embedded in alginate for repair of osteochondral defects. Arthoscopy 2000;16:571–7.

    Article  CAS  Google Scholar 

64. Muraglia A, Cancedda R, Quarto R . Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci 2000;113:1161–6.

    CAS  PubMed  Google Scholar 

65. Reynolds BA, Weiss S . Generation of neurones and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992;255:1707–10.

    Article  CAS  PubMed  Google Scholar 

66. Reynolds BA, Weiss S . Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol 1996;175:1–13.

    Article  CAS  PubMed  Google Scholar 

67. Lois C, Alvarez-Buylla A . Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurones and glia. Proc Natl Acad Sci USA 1993;90:2074–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

68. Palmer TD, Takahashi J, Gage FH . The adult rat hippocampus contains primordial neural stem cells. Mol Cell Neurosci 1997;8:389–404.

    Article  CAS  PubMed  Google Scholar 

69. Yandava BD, Billinghurst LL, Synder EY . Global cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci USA 1999;96:7029–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

70. Sheen VL, Arnold MA, Wang Y, Macklis JD . Neural precursor differentiation following transplantation into neocortex is dependent on intrinsic developmental state and receptor competence. Exp Neurol 1999;158:47–62.

    Article  CAS  PubMed  Google Scholar 

71. Suhonen JO, Peterson DA, Ray J, Gage FH . Differentiation of adult hippocampus-derived progenitor into olfactory neurones in vivo. Nature 1996;383:624–7.

    Article  CAS  PubMed  Google Scholar 

72. Grisham JW, Thorgeirsson SS . Liver stem cells. In: Potten CS, editor. Stem cells. London: Acadmic Press, 1997:233–82.

73. Fujio K, Evarts RP, Hu Z, Marsden ER, Thorgeirsson SS . Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in the adult rat. Lab Invest 1994;70:511–6.

    CAS  PubMed  Google Scholar 

74. Omori N, Omori M, Evarts RP, Teramoto T, Miller MJ, Hoang TN, et al. Partial cloning of rat CD34 cDNA and expression during stem cell-dependent liver regeneration in the adult rat. Hepatology 1997;26:720–7.

    Article  CAS  PubMed  Google Scholar 

75. Skoff RP, Knapp PE . The origins and lineages of macroglial cells. In: Kettenmann H, Ransom BR, editors. Neuroglia. New York: Oxford University Press, 1995:135–48.

76. Kitamura T, Miyake T, Fugita S . Genesis of resting microglia in the grey matter of mouse hippocampus. J Comp Neurol 1994;226:421–33.

    Article  Google Scholar 

77. Neuhaus J, Fedoroff S . Development of microglia in mouse neopallial cell cultures. Glia 1994;11:11–7.

    Article  CAS  PubMed  Google Scholar 

78. Perry VH, Gordon S . Macrophages and microglia in the nervous system. Trends Neurosci 1988;11:273–7.

    Article  CAS  PubMed  Google Scholar 

79. Ling EA, Wong WC . The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia 1993;7:9–18.

    Article  CAS  PubMed  Google Scholar 

80. Eglitis MA, Mezey E . Haematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 1997;94:4080–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

81. Campion DR . The muscle satellite cells: a review. Int Rev Cytol 1984;87:225–51.

    Article  CAS  PubMed  Google Scholar 

82. Schultz E, Lipton BH . Skeletal muscle satellite cells: changes in proliferation potential as a function of age. Mech Ageing Dev 1982;20:377–83.

    Article  CAS  PubMed  Google Scholar 

83. Grounds MD, Garrett KL, Lai MC, Wright WE, Beilharz MW . Identification of skeletal muscle precursor cells in vivo by use of MyoD1 and myogenin probes. Cell Tissue Res 1992;267:99–104.

    Article  CAS  PubMed  Google Scholar 

84. Wakitani S, Saito T, Caplan AL . Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 1995;18:1417–26.

    Article  CAS  PubMed  Google Scholar 

85. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998;279:1528–30.

    Article  CAS  PubMed  Google Scholar 

86. Williams JM, Daniel CW . Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol 1983;97:274–90.

    Article  CAS  PubMed  Google Scholar 

87. Ormerod EJ, Rudland PS . Cellular composition and organisation of ductal buds in developing rat mammary glands: evidence for morphological intermediates between epithelial and myoepithelial cells. Am J Anat 1984;170:631–52.

    Article  CAS  PubMed  Google Scholar 

88. Rudland PS . Histochemical organisation and cellular composition of ductal buds in developing human breasts: evidence of cytochemical intermediates between epithelial and myoepithelial cells. J Histochem Cytochem 1991;39:1471–84.

    Article  CAS  PubMed  Google Scholar 

89. Smith GH, Medina D . A morphologically distinct candidate for an epithelial stem cell in mouse mammary gland. J Cell Sci 1988;90:173–83.

    PubMed  Google Scholar 

90. Huang Y, Yang J, Wang XB, Becker FF, Gascoyne PR . The removal of human breast cancer cells from hematopoietic CD34+ stem cells by dielectrophoretic field-flow fractionation. J Haematother Stem Cell Res 1999;8:481–90.

    Article  CAS  Google Scholar 

91. Okumura A, Tokuda Y, Ohta M, Suzuki Y, Saito Y, Kuge S, et al. Autografting with peripheral blood CD34-positive cells following high-dose chemotherapy against breast cancer. Tokai J Exp Clin Med 1999;24:141–6.

    CAS  PubMed  Google Scholar 

92. Brasseur N, Menard I, Forget A, el Jastimi R, Hamel R, Molfino NA, et al. Eradication of multiple myeloma and breast cancer cells by TH9402-mediated photodynamic therapy: implication for clinical ex vivo purging of autologous stem cell transplants. Photochem Photobiol 2000;72:780–7.

    Article  CAS  PubMed  Google Scholar 

93. Shadduck RK, Zeigler ZR, Andrews DR, Gilmore GL, Lister J . Mobilisation and transplantation of peripheral blood stem cells. Stem Cells 1998;16(Suppl 1):145–58.

    Article  PubMed  Google Scholar 

94. Damon LE, Hu WW, Stockerl-Goldstein KE, Blume KG, Wolf JL, Gold E, et al. High-dose chemotherapy and haematopoietic stem cell rescue for breast cancer: experience in California. Biol Blood Marrow Transplant 2000;6:496–505.

    Article  CAS  PubMed  Google Scholar 

95. Genre D, Viens P, Gravis G, Bertucci F, Cowen D, Novakovitch G, et al. Outpatient sequential high dose alkylation with stem cell support for patients with advanced breast cancer: a phase I–II study. Anticancer Res 2000;20:2033–40.

    CAS  PubMed  Google Scholar 

96. Gupta S, Kumar L, Raju GM, Kochupillai V, Shukla DK . Autologous bone marrow/stem cell transplantation: initial experience at a north Indian referral centre. Natl Med J India 2000;13:61–6.

    CAS  PubMed  Google Scholar 

97. Ahmed T, Kancherla R, Qureshi Z, Mittelman A, Seiter K, Mannancheril A, et al. High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome. Bone Marrow Transplant 2000;25:1041–5.

    Article  CAS  PubMed  Google Scholar 

98. Stadmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, et al. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous haematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group. N Engl J Med 2000;13:1069–76.

    Google Scholar 

99. Miller SJ, Lavker RM, Sun TT . Keratinocyte stem cells of cornea, skin and hair follicles. In: Potten CS, editor. Stem cells. London: Academic Press, 1997:331–62.

100. Morris RJ, Fischer SM, Slaga TJ . Evidence that the centrally and peripherally located cells in the murine epidermal proliferative unit are two distinct cell populations. J Invest Dermatol 1985;84:277–81.

     Article  CAS  PubMed  Google Scholar 

101. Palovitch JH, Rizk-Rabin M, Jaffray P, Hoehn H, Poot M . Characteristics of homogeneously small keratinocytes from newborn rat skin: possible epidermal stem cells. Am J Physiol 1991;261:C964–72.

     Article  Google Scholar 

102. Bergstresser PR, Tigelaar RE, Streilein JW . Thy-1 antigen-bearing dendritic cells in murine epidermis are derived from bone marrow precursors. J Invest Dermatol 1984;83:83–7.

     Article  CAS  PubMed  Google Scholar 

103. Romani N, Tschachler E, Schuler G, Aberer W, Ceredig R, Elbe A, et al. Morphological and phenotypical characterisation of bone marrow-derived dendritic Thy-1 positive epidermal cells of the mouse. J Invest Dermatol 1985;85(Suppl 1):S91–5.

     Article  Google Scholar 

104. Young JW, Szabolcs P, Moore MA . Identification of dendritic cell colony-forming units among normal human CD34+ bone marrow progenitors that are expanded by c-kit-ligand and granulocyte/macrophage colony-stimuating factor and tumour necrosis factor alpha. J Exp Med 1995;182:1111–9.

     Article  CAS  PubMed  Google Scholar 

105. Gothelf Y, Hanau D, Tsur H, Sharon N, Sahar E, Cazenave JP, et al. T6 positive cells in the peripheral blood of burns patients: are they Langerhans cells precursors? J Invest Dermatol 1988;90:142–8.

     Article  CAS  PubMed  Google Scholar 

106. Stenevi V, Bjorklund A . Transplantation techniques of the study of regeneration in the central nervous system. Prog Brain Res 1978;48:101–12.

     Article  CAS  PubMed  Google Scholar 

107. McConnel P, Berry M . Regeneration of ganglion cell axons in the adult mouse retina. Brain Res 1982;241:362–5.

     Article  Google Scholar 

108. Silverman MS, Hughes SE . Transplantation of photoreceptors to light-damaged retina. Invest Ophthalmol Vis Sci 1989;30:1684–90.

     CAS  PubMed  Google Scholar 

109. Wang H, Kaplan HJ, Chan WC, Johnson M . The distribution and ontogeny of MHC antigens in murine ocular tissue. Invest Ophthalmol Vis Sci 1987;28:1383–9.

     CAS  PubMed  Google Scholar 

110. del Cerro M, Gash DM, Rao GN, Notter MF, Wiegand SJ, Gupta M . Intraocular retinal transplants. Invest Ophthalmol Vis Sci 1985;26:1182–5.

     CAS  PubMed  Google Scholar 

111. Turner JE, Blair JR . Newborn rat retinal cells transplanted into a retinal lesion site in adult host eye. Brain Res 1986;391:91–104.

     Article  CAS  PubMed  Google Scholar 

112. Aramant R, Seiler M, Turner JE . Donor age influences on the success of retinal grafts to adult rat retina. Invest Ophthalmol Vis Sci 1988;29:498–503.

     CAS  PubMed  Google Scholar 

113. Ghosh F, Arner K, Ehinger B . Transplant of full-thickness embryonic rabbit retina using pars plana virectomy. Retina 1998;18:136–42.

     Article  CAS  PubMed  Google Scholar 

114. Gouras P, Du J, Gelanze M, Kwun R, Kjeldbye H, Lopez R . Transplantation of photoreceptors labelled with tritiated thymidine into RCS rats. Invest Ophthalmol Vis Sci 1991;32:1704–7.

     CAS  PubMed  Google Scholar 

115. Lazar E, del Cerro M . A new procedure for multiple intraretinal transplantation into mammalian eyes. J Neurosci Methods 1992;43:157–69.

     Article  CAS  PubMed  Google Scholar 

116. Juliusson B, Bergstrom A, van Veen T, Ehinger B . Cellular organisation in retinal transplants using cell suspensions or fragments of embryonic retinal tissue. Cell Transplant 1993;2:411–8.

     Article  CAS  PubMed  Google Scholar 

117. Gouras P, Algvere P . Retinal cell transplant in the macular: new techniques. Vision Res 1996;36:4121–5.

     Article  CAS  PubMed  Google Scholar 

118. Seiler MJ, Aramant RB . Intact sheets of foetal retina transplanted to restore damaged rat retinas. Invest Ophthalmol Vis Sci 1998;39:2121–31.

     CAS  PubMed  Google Scholar 

119. Huang JC, Ishida M, Hersh P, Sugino IK, Zarbin MA . Preparation and transplantation of photoreceptor sheets. Curr Eye Res 1998;17:573–85.

     Article  CAS  PubMed  Google Scholar 

120. Ghosh F, Bruun A, Ehinger B . Graft-host connections in long-term full thickness embryonic rabbit retinal transplants. Invest Ophthalmol Vis Sci 1999;40:126–32.

     CAS  PubMed  Google Scholar 

121. Sharma RK, Bergstrom A, Zucker CL, Adolph AR, Ehinger B . Survival of long-term retinal cell transplants. Acta Ophthalmol Scand 2000;78:396–402.

     Article  CAS  PubMed  Google Scholar 

122. Aramant RB, Seiler MJ, Ball SL . Successful cotransplantation of intact sheets of foetal retina with retinal pigment epithelium. Invest Ophthalmol Vis Sci 1999;40:1557–64.

     CAS  PubMed  Google Scholar 

123. Woch G, Aramant RB, Seiler MJ, Sagdullaev BT, McCall MA . Retinal transplants restore evoked reponses in rats with photoreceptor degeneration. Invest Ophthalmol Vis Sci 2001;42:1669–76.

     CAS  PubMed  Google Scholar 

124. Aramant RB, Seiler MJ . Human embryonic retinal cell transplants in athymic immunodeficient rat hosts. Cell Transplant 1994;3:461–74.

     Article  CAS  PubMed  Google Scholar 

125. Seiler MJ, Aramant RB . Photoreceptor and glial markers in human embryonic retina and in human embryonic retinal transplants to rat retina. Brain Res Dev Brain Res 1994;80:81–95.

     Article  CAS  PubMed  Google Scholar 

126. DiLoerto DA, del Cerro C, Lazar ES, Cox C, del Cerro M . Storage of human foetal retina in opitsol prior to subretinal transplantation. Cell Transplant 1996;5:553–61.

     Article  Google Scholar 

127. DiLoreto DA, del Cerro C,. del Cerro M . Cyclosporine treatment promotes survival of human foetal neural retina transplanted to the subretinal space of the light-damaged Fischer 344 rat. Exp Neurol 1996;140:37–42.

     Article  CAS  PubMed  Google Scholar 

128. Little CW, Castillo B, DiLoreto DA, Cox C, Wyatt J, del Cerro C, et al. Transplantation of human foetal retinal pigment epithelium rescues photoreceptor cells from degeneration in the Royal College of Surgeons rat retina. Invest Ophthalmol Vis Sci 1996;37:204–11.

     CAS  PubMed  Google Scholar 

129. Kaplan HJ, Tezel TH, Berger AS, Wolf ML, del Priore LV . Human photoreceptor transplantation in retinitis pigmentosa: a safety study. Arch Ophthalmol 1997;115:1168–72.

     Article  CAS  PubMed  Google Scholar 

130. Humayun MS, de Juan E, del Cerro M, Dagnelie G, Radner W, Sadda SR, et al. Human neural retinal transplantation. Invest Ophthalmol Vis Sci 2000;41:3100–6.

     CAS  PubMed  Google Scholar 

131. Tropepe V, Coles BL, Chiasson BJ, Horsford DJ, Elia AJ, McInnes RR, van der Kooy D . Retinal stem cells in the adult mammalian eye. Science 2000;287:2032–6.

     Article  CAS  PubMed  Google Scholar 

132. Vogel G . Stem cells: new excitement, persistent questions. Nature 2000;290:1672–4.

     CAS  Google Scholar 

133. Nishida K, Kinoshita S, Ohashi Y, Kuwayama Y, Yamamoto S . Ocular surface abnormalities in aniridia. Am J Ophthalmol 1995;120:368–75.

     Article  CAS  PubMed  Google Scholar 

134. Tseng SC, Li DQ . Comparison of protein kinase C subtype expression between normal and aniridic human ocular surfaces: implications for limbal stem cell dysfunction in aniridia. Cornea 1996;15:168–78.

     Article  CAS  PubMed  Google Scholar 

135. Fujishima H, Shimazaki J, Tsubota K . Temporary corneal stem cell dysfunction after radiation therapy. Br J Ophthalmol 1996;80:911–4.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

136. Holland EJ . Epithelial transplantation for the management of severe ocular surface disease. Trans Am Ophthalmol Soc 1996;94:677–743.

     CAS  PubMed  PubMed Central  Google Scholar 

137. Dua HS . The conjunctiva in corneal epithelial wound healing. Br J Ophthalmol 1998;82:1407–11.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

138. Dua HS, Azuara-Blanco A . Allo-limbal transplantation in patients with limbal stem cell deficiency. Br J Ophthalmol 1999;83:414–9.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

139. Dua HS, Azuara-Blanco A . Autologous limbal transplantation in patients with unilateral corneal stem cell deficiency. Br J Ophthalmol 2000;84:273–8.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

140. Azuara-Blanco A, Dua HS, Sloper M . Treatment of corneal stem cell deficiency. Invest Ophthalmol Vis Sci 1999;40:S336.

     Google Scholar 

141. Kenyon KR, Tseng SC . Limbal autograft transplantation for ocular surface disorders. Ophthalmology 1989;96:709–23.

     Article  CAS  PubMed  Google Scholar 

142. Jenkins C, Tuft S, Liu C, Buckley R . Limbal transplantation in the management of chronic contact-lens-associated epitheliopathy. Eye 1993;7:629–33.

     Article  PubMed  Google Scholar 

143. Kenyon KR, Rapoza PA . Limbal allograft transplantation for ocular surface disorders. Ophthalmology 1995;102:S101–2.

     Article  Google Scholar 

144. Tsai RJ, Li LM, Chen JK . Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. N Engl J Med 2000;343:86–93.

     Article  CAS  PubMed  Google Scholar 

145. Gris O, Guell JL, del Campo Z . Limbal-conjunctival autograft transplantation for the treatment of recurrent pterygium. Ophthalmology 2000;107:270–3.

     Article  CAS  PubMed  Google Scholar 

146. Copeland RA Jr, Char DH . Limbal autograft reconstruction after conjunctival squamous cell carcinoma. Am J Ophthalmol 1990;110:412–5.

     Article  PubMed  Google Scholar 

147. Morgan S, Murray A . Limbal autotransplantation in the acute and chronic phases of severe chemical injuries. Eye 1996;10:349–54.

     Article  PubMed  Google Scholar 

148. Frucht-Pery J, Siganos CS, Solomon A, Scheman L, Brautbar C, Zauberman H . Limbal cell autograft transplantation for severe ocular surface disorders. Graefes Arch Clin Exp Ophthalmol 1998;236:582–7.

     Article  CAS  PubMed  Google Scholar 

149. Costar DJ, Aggarwal RK, Williams KA . Surgical management of ocular surface disorders using conjunctival and stem cell allografts. Br J Ophthalmol 1995;79:977–82.

     Article  Google Scholar 

150. Theng JT, Tan DT . Combined penetrating keratoplasty and limbal allograft transplantation for severe corneal burns. Opthalmic Surg Lasers 1997;28:765–8.

     CAS  Google Scholar 

151. Williams KA, Brereton HM, Aggarwal R, Sykes PJ, Turner DR, Russ GR, Costar DJ . Use of DNA polymorphisms and the polymerase chain reaction to examine the survival of a human limbal stem cell allograft. Am J Opthalmol 1995;120:342–50.

     Article  CAS  Google Scholar 

152. Williams KA, Costar DJ . Rethinking immunological privilege: implications for corneal and limbal stem cell transplantation. Mol Med Today 1997;3:495–501.

     Article  CAS  PubMed  Google Scholar 

153. Daya SM, Bell RW, Habib NE, Powell-Richards A, Dua HS . Clinical and pathologic findings in human keratolimbal allograft rejection. Cornea 2000;19:443–50.

     Article  CAS  PubMed  Google Scholar 

154. Tsubota K, Toda I, Saito, Shinozaki N, Shimazaki J . Reconstruction of the corneal epithelium by limbal allograft transplantation for severe ocular disorders. Ophthalmology 1995;102:1486–96.

     Article  CAS  PubMed  Google Scholar 

155. Tsubota K, Satake Y, Shimazaki J . Treatment of severe dry eye. Lancet 1996;348:123.

     Article  CAS  PubMed  Google Scholar 

156. Tan DT, Ficker LA, Buckley RJ . Limbal transplantation. Ophthalmology 1996;103:29–36.

     Article  CAS  PubMed  Google Scholar 

157. Sloper CM, Powell RJ, Dua HS . Tacrolimus (FK506) in the treatment of posterior uveitis refractory to cyclosporine. Ophthalmology 1999;106:723–8.

     Article  CAS  PubMed  Google Scholar 

158. Reh TA, Kljavin IJ . Age of differentiation determines rat retinal germinal cell phenotype: induction of differentiation by dissociation. J Neurosci 1989;9:4179–89.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

159. Altshuler D, Lo Turco JL, Rush J, Cepko C . Taurine promotes the differentiation of a vertebrate retinal cell type in vitro. Development 1993;119:1317–28.

     CAS  PubMed  Google Scholar 

160. Kelly MW, Turner JK, Reh TA . Retinoic acid promotes differentiation of photoreceptors in vitro. Development 1994;120:2091–102.

     Google Scholar 

161. Ahmad I, Dooley CM, Thoreson WM, Rogers JA, Afiat S . In vitro analysis of a mammalian retinal progenitor that gives rise to neurones and glia. Brain Res 1999;831:1–10.

     Article  CAS  PubMed  Google Scholar 

162. Ahmad I, Tang L, Pham H . Identification of neural progenitors in the adult mammalian eye. Biochem Biophys Res Commun 2000;270:517–21.

     Article  CAS  PubMed  Google Scholar 

163. Anchan R, Angello J, Balliet A, Walker M, Reh TA . EGF and TGF stimulate retinal germinal neuroepithelial proliferation. Neuron 1991;6:1–20.

     Article  Google Scholar 

164. Lilien L, Cepko C . Control of proliferation in the retina: temporal changes in responsiveness to FGF and TGF. Development 1992;115:253–66.

     Google Scholar 

165. Reh TA . Cellular interactions determine neuronal phenotypes in rodent retinal cultures. J Neurobiol 1992;23:1067–83.

     Article  CAS  PubMed  Google Scholar 

166. Araki M, Iida Y, Taketani S, Watanabe M, Ohta K, Saito J . Characterisation of photoreceptor cell differentiation in the rat retinal cell culture. Dev Biol 1987;124:239–47.

     Article  CAS  PubMed  Google Scholar 

167. Sparrow JR, Hicks D, Barnstable CJ . Cell commitment and differentiation in explants of embryonic rat neural retina: comparison with the development potential of dissociated retina. Dev Brain Res 1990;51:69–84.

     Article  CAS  Google Scholar 

168. Watanabe T, Raff MC . Rod photoreceptor development in vitro: intrinsic properties of proliferating neuroepithelial cells change as development proceeds in the rat retina. Neuron 1990;4:461–7.

     Article  CAS  PubMed  Google Scholar 

169. Kelly MW, Turner JK, Reh TA . Ligands of steroid/thyroid receptors induce cone photoreceptors in vertebrate retina. Development 1995;121:3777–85.

     Google Scholar 

170. Levine EM, Roelink H, Turner J, Reh TA . Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro. J Neurosci 1997;17:6277–88.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

171. Chacko DM, Rogers JA, Turner JE, Ahmad I . Survival and differentiation of cultured retinal progenitors transplanted in the subretinal space of the rat. Biochem Biophys Res Commun 2000;268:842–6.

     Article  CAS  PubMed  Google Scholar 

172. Kurimoto Y, Shatos MA, Young MJ . Transplantation of retinal progenitor cells from GFP transgenic mice to the retina of normal and RD mice. Invest Ophthalmol Vis Sci 2001:42:S198.

     Google Scholar 

173. Bovolenta P, Frade JM, Marti E, Rodiiguez-Pena MA, Barde YA, Rodriguez-Tebar A . Neurotrophin-3 antibodies disrupt the normal development of the chick retina, J Neurosci 1996;16:4402-10.Neurotrophin-3 antibodies disrupt the normal development of the chick retina, J Neurosci 1996;16:4402–10.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

174. Ma C, Zhou Y, Beachy PA, Moses K . The segment polarity gene hedgehog is required for progression of the morphogenic furrow in the developing Drosophua eye. Cell 1993;75:927–38.

     Article  CAS  PubMed  Google Scholar 

175. Ruberte E, Dolle P, Chambon P, Morriss-Kay G . Retinoic acid receptors and cellular retinoid binding proteins. II. Their differential pattern of transcription during early morphogenesis in mouse embryos. Development 1991;111:45–60.

     CAS  PubMed  Google Scholar 

176. Rodriguez-Tebar A, del la Rosa E, Arribas A . Neurotrophin-3 receptors in the developing chicken retina. Eur J Biochem 1993;211:789–94.

     Article  CAS  PubMed  Google Scholar 

177. de la Rosa EJ, Arribas A, Frade AJM, Rodriguez-Tebar A . Role of neurotrophins in the control of neural development neurotrophin-3 promotes both neuron differentiation and survival of cultured chick retinal cells. Neuroscience 1994;58:347–52.

     Article  CAS  PubMed  Google Scholar 

178. Roberts VJ, Barm SL Expression of messenger ribonucleic acids encoding the inhibin/activin system during mid and late gestation rat embryogenesis. Endocrinology 1994;134:914–23.

     Article  CAS  PubMed  Google Scholar 

179. Hammerschmidt M, Brook A, McMahan AP . The world according to the hedgehog. Trends Genet 1997;13:14–21.

     Article  CAS  PubMed  Google Scholar 

180. Tabata T, Kornberg TB . Hedgehog is a signalling protein with a key role in patterning Drosophilia imaginal disc. Cell 1990;76:89–102.

     Article  Google Scholar 

181. Heberlein U, Singh CM, Luk AY, Donohoe TJ . Growth and differentiation in the Drosaphila eye coordinated by hedgehog. Nature 1995;373:709–11.

     Article  CAS  PubMed  Google Scholar 

182. Dominguez M, Hafen E . Hedgehog directly controls initiation and propagation of retinal differentiation in the Drosaphila eye. Genes Dev 1997;11:3254–64.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

183. Dutton R, Yamada T, Turnley A, Bartlett PF, Murphy M . Sonic hedgehog promotes neuronal differentiation of murine spinal cord precursors and collaborates with neurotrophin-3 to induce Islet-1. J Neurosci 1999;19:2601–8.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

184. Furukawa T, Morrow EM, Cepko CL Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Cell 1997;91:531–41.

     Article  CAS  PubMed  Google Scholar 

185. Chen S, Wang QL, Nie Z, Sun H, Lennon G, Copeland NG, Gilbert DJ, Jenkins NA, Zack DJ . Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes. Neuron 1997;19:1017–30.

     Article  CAS  PubMed  Google Scholar 

186. Sakamoto K, Oishi K, Okada T, Onuma Y, Yokoyama K, Sugimoto K, et al. Molecular cloning of the cone-rod homeobox gene (Crx) from the rat and its temporal expression pattern in the retina under a daily light-dark cycle. Neurosci Lett 1999;261:101–4.

     Article  CAS  PubMed  Google Scholar 

187. Freund CL, Gregory-Evans CY, Furukawa T, Papaioannou M, Looser J, Ploder L, et al. Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (Crx) essential for the maintenance of the photoreceptor. Cell 1997;91:543–53.

     Article  CAS  PubMed  Google Scholar 

188. Furukawa T, Morrow EM, Li T, Davis FC, Cepko CI . Retinopathy and attenuated circadian entrainment in Crxdeficient mice. Nat Genet 1999;23:466–70.

     Article  CAS  PubMed  Google Scholar 

189. Swain PK, Chen S, Wang QL, Affatigato LM, Coats CL, Brady KD, et al. Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. Neuron 1997;19:1329–36.

     Article  CAS  PubMed  Google Scholar 

190. Sohocki MM, Sullivan LS, Mintz-Hitnner HA, Birch D, Heckenlively JR, Freund CL, et al. A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene. Am J Hum Genet 1998;63:1307–15.

     Article  CAS  PubMed  PubMed Central  Google Scholar 

191. Freund CL, Wang QL, Chen S, Muskat BL, Wiles CD, Sheffield VC, et al. De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. Nat Genet 1998;18:311–2.

     Article  CAS  PubMed  Google Scholar 

192. Silva E, Yang JM, Li Y, Dharmaraj S, Sundin OH, Maumenee IH . A CRX null mutation is associated with both Leber congenital amaurosis and a normal ocular phenotype. Invest Ophthalmol Vis Sci 2000;41:2076–9.

     CAS  PubMed  Google Scholar 

193. Tzekov RT, Liu Y, Sohocki MM, Zack DJ, Daiger SP, Heckenlively JR, et al. Autosomal dominant retinal degeneration and bone loss in patients with a 12bp deletion in the CRX gene. Invest Ophthalmol Vis Sci 2001;42:1319–27.

     CAS  PubMed  Google Scholar 

194. Haruta M, Takahashi M, Kanegae Y, Saito I . Crx promotes retinal stem cell differentiation into photoreeeptors. Invest Ophthalmol Vis Sci 2001;42:S198.

     Google Scholar 

195. Takahashi M, Palmer TD, Takahashi J, Gage FH . Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina. Mol Cell Neurosci 1998;12:340–8.

     Article  CAS  PubMed  Google Scholar 

196. Lauritzen DB, Kurimoto Y, Gage FH, Klassen H, Young MJ . Retinal transplantation of neural progenitor cells in rat transgenie for mutant rhodopsin. Invest Ophthalml Vis Sci 2001;42:S198.

     Google Scholar 

197. Young MJ, Ray J, Whiteley SJ, Klassen H, Gage FH . Neuronal differentiation and morphological integrations of hippoeampal progenitor cells transplanted to the retina of immature and mature dystrophic rats. Mol Cell Neurosci 2000;16:197–205.

     Article  CAS  PubMed  Google Scholar 

198. Nishida A, Takahashi M, Tanihara H, Nakano I, Takahashi JB, Mizoguchi A, et al. Incorporation and differentiation of hippocampus-derived neural stem cells transplanted in injured adult rat retina. Invest Ophthalmol Vis Sci 2000;41:4268–74.

     CAS  PubMed  Google Scholar 

199. Mizumoto H, Mizumoto K, Whiteley SJ, Shatos M, Klassen H, Young MJ, Transplantation of human neural progenitor cells to the vitreous cavity of the Royal College of Surgeons rat. Cell Transplant 2001;10:223–33.

     Article  CAS  PubMed  Google Scholar 

Download references