Skip to main content
PMC home page
Cytotechnology logoLink to Cytotechnology
. 2004 Mar;44(3):125–141. doi: 10.1007/s10616-004-2067-6

Stem cells: From embryology to cellular therapy? An appraisal of the present state of art

Sandro Eridani 1,✉, Vittorio Sgaramella 2, Lidia Cova 3
PMCID: PMC3449482  PMID: 19003235

Abtract

A series of publications has dealt in the last years with topics as the isolation, properties and applications of animal stem cells (Weissman 2000. Cell 100: 157–168; Weissman 2002. N. Engl. J. Med. 346: 1567–1579; Lovell-Badge 2001. Nature 414: 88–91; Marshak et al. 2001. Stem Cell Biology. Cold Spring Harbor Laboratory Press, New york; Eridani 2002. J. Roy. Soc. Med. 95: 5–8; Borge and Evers 2003. Cytotechnology 41: 59–68; Sgaramella 2003. Cytotechnology 41: 69–73), however, the bonanza of experimental data recently accumulating have raised such an amount of controversial views and discussions that time perhaps has come for a reassessment of the basic facts in this peculiar area of research and an evaluation of possible, not unrealistic, implications.

Keywords: Cellular therapy, Embriology, Stem cells

Full Text

The Full Text of this article is available as a PDF (377.3 KB).

References

  1. Akashi K., Traver D., Miyamoto T., Weissmann I.L. A clonogenic common myeloid progenitor which gives rise to all myeloid lineages. Nature. 2000;404:193–197. doi: 10.1038/35004599. [DOI] [PubMed] [Google Scholar]
  2. Almeida-Porada G., Shabrawy D., Porada C., Zanjani E.D. Differentiative potential of human metanephric mesenchimal cells. Exp. Haematol. 2002;30:1454–1462. doi: 10.1016/S0301-472X(02)00967-0. [DOI] [PubMed] [Google Scholar]
  3. Andrews P.W. Teratocarcinomas and human embryology: pluripotent human EC lines. ABMIS. 1998;106:158–168. doi: 10.1111/j.1699-0463.1998.tb01331.x. [DOI] [PubMed] [Google Scholar]
  4. Appelbaum F.R. Allogeneic haematopoietic stem cell transplantation for acute leukemia. Sem. Oncol. 1997;24:114–123. [PubMed] [Google Scholar]
  5. Balsam L.B., Wagers A.J., Christensen J.L., et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischemic myocardium. Nature. 2004;428:668–673. doi: 10.1038/nature02460. [DOI] [PubMed] [Google Scholar]
  6. Besinger W., Weaver C.H., Appelbaum F.R., et al. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant granulocyte colony stimulating factor. Blood. 1995;85:1665–1668. [PubMed] [Google Scholar]
  7. Borge O.J., Evers K. Aspects on properties, use and ethical considerations of embryonic stem cells. A short review. Cytotechnology. 2003;41:59–68. doi: 10.1023/A:1024862403630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bottai D., Fiocco R., Gelain F., et al. Neural stem cells in the adult nervous system. J. Hematother. Stem Cell Res. 2003;12:655–670. doi: 10.1089/15258160360732687. [DOI] [PubMed] [Google Scholar]
  9. Brandenberger R., Wei H., Zhangh S., et al. Transcriptome characterization elucidates signalling networks that control human ES cell growth and differentiation. Nat. Biotechnol. 2004;22:707–716. doi: 10.1038/nbt971. [DOI] [PubMed] [Google Scholar]
  10. Brugger W., Heimfeld S., Berenson R.J., et al. Reconstitution of hematopoiesis after high-dose chemotherapy by autologous progenitor cells generated ex vivo. N. Engl. J. Med. 1995;333:283–287. doi: 10.1056/NEJM199508033330503. [DOI] [PubMed] [Google Scholar]
  11. Brivanlou A.H., Gage F.H., Jaenisch R., et al. Setting standards for human embryonic stem cells. Science. 2003;300:913–916. doi: 10.1126/science.1082940. [DOI] [PubMed] [Google Scholar]
  12. Broxmeyer H.E., Douglas G.W., Hangoe G., et al. Human umbilical cord blood as a potential source of transplantable haemopoietic stem cells. Proc. Natl. Acad. Sci. USA. 1989;86:328–332. doi: 10.1073/pnas.86.10.3828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Byrne J., Simonsson S., Western P.S., Gurdon J.B. Adult nuclei of mammalian somatic cells are directly reprogrammed to oct-4 stem cell gene expression by amphibian oocytes. Curr. Biol. 2003;13:1206–1213. doi: 10.1016/S0960-9822(03)00462-7. [DOI] [PubMed] [Google Scholar]
  14. Camargo F.D., Green R., Capetenaki Y., et al. Single haematopoietic stem cells generate skeletal muscle through myeloid intermediates. Nat. Med. 2003;9:1520–1527. doi: 10.1038/nm963. [DOI] [PubMed] [Google Scholar]
  15. Cancedda R., Castagnola P., Cancedda F.D., et al. Developmental control of chondrogenesis and osteogenesis. Int. J. Dev. Biol. 2000;44:707–714. [PubMed] [Google Scholar]
  16. Caterson E.J., Nesti E.L., Danielson K.G., Tuan R.S. Human marrow-derived mesenchymal progenitor cells: isolation, cultureexpansion and analysis of differentiation. Mol. Biotechnol. 2002;20:245–256. doi: 10.1385/MB:20:3:245. [DOI] [PubMed] [Google Scholar]
  17. Chen S., Zhang Q., Wu P., et al. Dedifferentiation of lineage-committed cells by a small molecule. J. Am. Chem. Soc. 2004;126:410–411. doi: 10.1021/ja037390k. [DOI] [PubMed] [Google Scholar]
  18. Chien K.R. Stem cells: lost in translation. Nature. 2004;428:607–608. doi: 10.1038/nature02500. [DOI] [PubMed] [Google Scholar]
  19. Cibelli J.B., Grant K., Chapman K.B., et al. Parthenogenetic stem cells in non human primates. Science. 2002;295:819. doi: 10.1126/science.1065637. [DOI] [PubMed] [Google Scholar]
  20. Clark A.D., Jorgensen H.G., Mountford J., Holyoake T. Isolation and therapeutic potential of human haemopoietic tem cells. Cytotechnology. 2003;41:111–131. doi: 10.1023/A:1024822722285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Clement A.M., Nguyen M.D., Roberts E.A., et al. Wild type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science. 2003;302:113–117. doi: 10.1126/science.1086071. [DOI] [PubMed] [Google Scholar]
  22. Converse J.M., Casson P.R. The historical background of transplantation. In: Rapaport F.T., Dausset J., editors. Human Transplantation. New York: Grune and Stratton; 1968. [Google Scholar]
  23. Courbel S.Y., Lee A., Duenas J., et al. Contribution of haemopoietic stem cells to skeletal muscle. Nat. Med. 2003;9:1528–1532. doi: 10.1038/nm959. [DOI] [PubMed] [Google Scholar]
  24. Cowan C.M., Shi Y.Y., Aalami O.O., et al. Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat. Biotechnol. 2004;22:560–567. doi: 10.1038/nbt958. [DOI] [PubMed] [Google Scholar]
  25. Derubeis A.R., Cancedda R. Bone marrow stromal cells in bone engineering: limitations and recent advances. Ann. Biom. Eng. 2004;32:160–165. doi: 10.1023/B:ABME.0000007800.89194.95. [DOI] [PubMed] [Google Scholar]
  26. De Wynte E.A., Coutinho E.H., Pei X., et al. Comparison of purity and enrichment of CD34+ cells from bone marrow, umbilical cord and peripheral blood using five separation systems. Stem Cells. 1995;13:524–532. doi: 10.1002/stem.5530130510. [DOI] [PubMed] [Google Scholar]
  27. De Wynter E.A. What is the future for cord blood stem cells? I Cytotechnology. 2003;41:133–138. doi: 10.1023/A:1024874706356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ding S., Schultz P.G. A role for chemistry in stem cell biology. Nat. Biotechnol. 2004;22:833–840. doi: 10.1038/nbt987. [DOI] [PubMed] [Google Scholar]
  29. Dua H.S., Azuara-Blanco J. Limbal stem cells of the corneal epithelium. Surv. Ophtalm. 2000;44:415–424. doi: 10.1016/S0039-6257(00)00109-0. [DOI] [PubMed] [Google Scholar]
  30. Dunwald M., Tomanek-Chalkley A., Alexandrounas D., et al. Isolating a pure population of epidermal stem cells for use in tissue engineering. Exp. Dermat. 2001;10:45–54. doi: 10.1034/j.1600-0625.2001.100106.x. [DOI] [PubMed] [Google Scholar]
  31. Eglitis M.A., Mezey E. Haemopoietic cell differentiation into both microglia and macroglia in the brains of adult mice. Proc. Natl. Acad. Sci. 1997;94:4080–4085. doi: 10.1073/pnas.94.8.4080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Emerson S.G. Ex vivo expansion of hemopoietic precursors, progenitors and stem cells: the next generation of cellular therapeutics. Blood. 1996;87:3082–3088. [PubMed] [Google Scholar]
  33. Eridani S. Stem cells for all seasons? Experimental and clinical issues. J. Roy. Soc. Med. 2002;95:5–8. doi: 10.1258/jrsm.95.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Eridani S., Morali F. Identification of haemopoietic stem cells. Cytotechnology. 1993;11:101–106. doi: 10.1007/BF00748998. [DOI] [PubMed] [Google Scholar]
  35. Eridani S., Dudley J.M., et al. Erytropoietic colonies in a serum-free system: results in PPP and in thrombocythemia. Brit. J. Haematol. 1987;67:387–391. doi: 10.1111/j.1365-2141.1987.tb06158.x. [DOI] [PubMed] [Google Scholar]
  36. Eridani S., Mazza U., Massaro P., et al. Cytokine effect on ex vivo expansion of haemopoietic stem cells from different human sources. Biotherapy. 1998;11:291–296. doi: 10.1023/A:1008081708054. [DOI] [PubMed] [Google Scholar]
  37. Erlebacher A., Filvaroff E.H., Gitelman S.E., Derynck R. Toward a molecular understanding of skeletal development. Cell. 1995;80:371–378. doi: 10.1016/0092-8674(95)90487-5. [DOI] [PubMed] [Google Scholar]
  38. Evans M.I., Kaufmann M.H. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292:154–156. doi: 10.1038/292154a0. [DOI] [PubMed] [Google Scholar]
  39. Farag S.S. 2002. Therapeutic applications of immunomagnetic cell selection: a review. Eur. Cells Mater. suppl.2: 37-40
  40. Ferrari G., Cusella Deangelis G., Coletta M., et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 1998;179:1528–1530. doi: 10.1126/science.279.5356.1528. [DOI] [PubMed] [Google Scholar]
  41. Flake A.W., Zanjani E.D. In utero haemopoietic stem cell transplantation: ontogenic opportunities and biologic barriers. Blood. 1999;94:2179–2191. [PubMed] [Google Scholar]
  42. Fuchs E., Segre E.A. Stem cells: a new lease of life. Cell. 2000;100:143–155. doi: 10.1016/S0092-8674(00)81691-8. [DOI] [PubMed] [Google Scholar]
  43. Gonda K., Fowler J., Katoku-Kikyo N., et al. Reversible disassembly of somatic nucleoli by the germ cell proteins FRGY2a and FRGY2b. Nat. Cell Biol. 2003;5:205–210. doi: 10.1038/ncb939. [DOI] [PubMed] [Google Scholar]
  44. Grompe M. The role of bone marrow stem cells in liver regeneration. Semin. Liver Dis. 2003;23:363–372. doi: 10.1055/s-2004-815560. [DOI] [PubMed] [Google Scholar]
  45. Hakelien A.M., Landsverk H.B., Robl J.M., Skalhegg B.S., Collas P. Reprogramming fibroblasts to express t-cell functions using cell extracts. Nat. Biotech. 2002;20:466–480. doi: 10.1038/nbt0502-460. [DOI] [PubMed] [Google Scholar]
  46. Handgretinger R., Gordon P.R., Leimig T., et al. Biology and plasticity of CD133+ hemopoietic stem cells. Ann. N.Y. Acad. Sci. 2003;996:141–151. doi: 10.1111/j.1749-6632.2003.tb03242.x. [DOI] [PubMed] [Google Scholar]
  47. Harrison D.E., Lerner C., Hoppe P.C., et al. Large numbers of primitive stem cells are active simultaneously in aggregated embryo chimeric mice. Blood. 1987;69:773–777. [PubMed] [Google Scholar]
  48. Hess D., Martin M., Sakano S., et al. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat. Biotech. 2003;21:763–770. doi: 10.1038/nbt841. [DOI] [PubMed] [Google Scholar]
  49. Holland E.J., Schwartz G.S. Epithelial stem cell transplantation for severe ocular surface disease. New Engl. J. Med. 1999;40:1752–1753. doi: 10.1056/NEJM199906033402208. [DOI] [PubMed] [Google Scholar]
  50. Hows J.M. Status of umbilical cord clood transplantation in the year 2001. N. Engl. J. Med. 2001;344:1860–1861. doi: 10.1056/NEJM200106143442410. [DOI] [PubMed] [Google Scholar]
  51. Hwang W.S., Ryu Y.J., Park J.H., et al. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science. 2004;303:1669–1674. doi: 10.1126/science.1094515. [DOI] [PubMed] [Google Scholar]
  52. Ivanova B.N., Dimos J.T., Schaniel C., et al. A stem cell molecular signature. Science. 2002;298:601–607. doi: 10.1126/science.1073823. [DOI] [PubMed] [Google Scholar]
  53. Johnson J., Canning J., Kaneko T., et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428:145–150. doi: 10.1038/nature02316. [DOI] [PubMed] [Google Scholar]
  54. Kang H.J., Kim H.S., Zhang S.Y., et al. Effect of intracoronary infusion of peripheral blood stem cells mobilized by G-CSF on left ventricular systolic function. Lancet. 2004;363:751–756. doi: 10.1016/S0140-6736(04)15689-4. [DOI] [PubMed] [Google Scholar]
  55. Kirschstein R. and Skirboll L. 2001. Stem Cells. Scientific Progress and Future Research Directions, NIH, Appendix E-I.
  56. Koc O.N., Lazarus H.M. Mesenchymal stem cells: heading into the clinic. Bone Marrow Transpl. 2001;27:235–239. doi: 10.1038/sj.bmt.1702791. [DOI] [PubMed] [Google Scholar]
  57. Kondo M., Weissmann L., Akashi K. Identification of clonogenic common lymphoid progenitor in mouse bone marrow. Cell. 1997;91:661–672. doi: 10.1016/S0092-8674(00)80453-5. [DOI] [PubMed] [Google Scholar]
  58. Kramer J., Hegert C., Hargus G., Rohwedel J. Chondrocytes derived from mouse embryonal stem cells. Cytotechnology. 2003;41:177–187. doi: 10.1023/A:1024835025011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Krause D.S., Theise N.D., Collector M.I., et al. Multi-organ, multilineage engrafment by a single bone marrow-derived stem cell. Cell. 2001;105:369–377. doi: 10.1016/S0092-8674(01)00328-2. [DOI] [PubMed] [Google Scholar]
  60. Lagasse E., Connors H., AI-dhalimy M., et al. Purified haemopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 2000;6:1229–1334. doi: 10.1038/81326. [DOI] [PubMed] [Google Scholar]
  61. Laitha L. Concepts of stem cells. Differentiation. 1979;14:23–34. doi: 10.1111/j.1432-0436.1979.tb01007.x. [DOI] [PubMed] [Google Scholar]
  62. Lebkowski J.S., Gold J., Xu C., et al. Human embryonic stem cells: culturedifferentiation and genetic modification for genetic medicine application. Cancer J. 2001;7(Suppl. 2):83–93. [PubMed] [Google Scholar]
  63. Lechner A., Yang Y., et al. No evidence for significant transdifferentiation of bone marrow into pancreatic β cells in vivo. Diabetes. 2004;53:616–624. doi: 10.2337/diabetes.53.3.616. [DOI] [PubMed] [Google Scholar]
  64. Li A., Pouliot N., Redvers R., Kaur P. Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny. J. Clin. Invest. 2004;113:390–400. doi: 10.1172/JCI200419140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Lovell-Badge R. The future for stem cell research. Nature. 2001;414:88–91. doi: 10.1038/35102150. [DOI] [PubMed] [Google Scholar]
  66. Lu P., Jones L., Snyder E.Y., Tuszynski M.H. Neural stem cells costitutively secrete neurotrophic factors and promote extensive host axonal growth after spinal cord injury. Exp. Neurol. 2003;181:115–129. doi: 10.1016/S0014-4886(03)00037-2. [DOI] [PubMed] [Google Scholar]
  67. Lucas J.J., Terada N. Cell fusion and plasticity. Cytotechnology. 2003;41:103–109. doi: 10.1023/A:1024870605447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Mangi A.A., Noiseaux N., Kong D., et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nature Med. 2003;9:1195–1201. doi: 10.1038/nm912. [DOI] [PubMed] [Google Scholar]
  69. Marks J. Mutant stem cells may seed cancer. Science. 2003;301:1308–1310. doi: 10.1126/science.301.5638.1308. [DOI] [PubMed] [Google Scholar]
  70. Marshak D.R., Gottlieb D., Gardner R.L. In Stem Cell Biology. New York: Cold Spring Harbor Laboratory Press; 2001. pp. 1–16. [Google Scholar]
  71. Maslov A.Y., Barone T.A., Plunkett R.J., Pruitt S.C. Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice. J. Neurosci. 2004;24:1726–1733. doi: 10.1523/JNEUROSCI.4608-03.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Mayani H., Lansdorp P.M. Proliferation of individual haematopoitic progenitors purigied from umbilical cord blood. Exp. Haematol. 1995;23:1453–1462. [PubMed] [Google Scholar]
  73. Mc Gann C.J., Odelbergs J., Keating M. Mammalian myotube dedifferentiation induced by newt regeneration extracts. Proc. Natl. Acad. Sci. USA. 2001;98:13699–13704. doi: 10.1073/pnas.221297398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Migliaccio A.R., Campisi S., Migliaccio G. Standardization of progenitor cell assay for cord blood banking. Annali Ist. Sup. Sanità. 2001;37:595–600. [PubMed] [Google Scholar]
  75. Murry C.E., Soonpaa M.H., Reinecke H., et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428:664–668. doi: 10.1038/nature02446. [DOI] [PubMed] [Google Scholar]
  76. Nishikawa S.I. A complex linkage in the developmental pathway of endothelial and haematopoietic cells. Curr. Opin. Cell Biol. 2001;13:673–678. doi: 10.1016/S0955-0674(00)00270-2. [DOI] [PubMed] [Google Scholar]
  77. Nusse R. WNT targets: repression and activation. Trend. Genet. 1999;15:1–3. doi: 10.1016/S0168-9525(98)01634-5. [DOI] [PubMed] [Google Scholar]
  78. Odelberg S.J., Kollhoff A., Keating M.T. Dedifferentiation of mammalian myotubes induced by msx1. Cell. 2000;103:1099–1109. doi: 10.1016/S0092-8674(00)00212-9. [DOI] [PubMed] [Google Scholar]
  79. Odorico J.S., Kaufman D.S., Thompson G.A. Multilineage differentiation from human embryonic stem cell lines. Stem Cells. 2001;19:193–204. doi: 10.1634/stemcells.19-3-193. [DOI] [PubMed] [Google Scholar]
  80. Orlic D., Kajstura J., Chimenti S., et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410:701–705. doi: 10.1038/35070587. [DOI] [PubMed] [Google Scholar]
  81. Osawa M., Hamada K., Hamada H., Nagauchi H. Long-term lympho-haemopoietic reconstitution by a single CD34-low/negative haematopoietic stem cell. Science. 1996;273:242–245. doi: 10.1126/science.273.5272.242. [DOI] [PubMed] [Google Scholar]
  82. Ourednik J., Ourednik V., Lynch W.P., et al. Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nat. Biotech. 2002;20:1103–1110. doi: 10.1038/nbt750. [DOI] [PubMed] [Google Scholar]
  83. Peng H., Wright V., Usas A., et al. Synergistic enhancement of bone formation and healing by stem cell expressed VEGF and bone morphogenetic protein-4. J. Clin. Invest. 2002;110:751–759. doi: 10.1172/JCI200215153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Pera M.F., Cooper S., Mills J., Parrington J.M. Isolation and chracterization of a multipotent clone of embryonic carcinoma stem cells. Differentiation. 1989;42:10–23. doi: 10.1111/j.1432-0436.1989.tb00602.x. [DOI] [PubMed] [Google Scholar]
  85. Perka C., Schultz O., Spitzer R.S., et al. Segmental bone repair by tissue-engineered periosteal cell transplants with bioresorbable fleece and fibrin scaffolds in rabbits. Biomaterials. 2000;21:1145–1153. doi: 10.1016/S0142-9612(99)00280-X. [DOI] [PubMed] [Google Scholar]
  86. Petersen B.E., Bowen W.C., Patrene K.D., et al. Bone marrow as potential source of hepatic oval cells. Science. 1999;284:1168–1170. doi: 10.1126/science.284.5417.1168. [DOI] [PubMed] [Google Scholar]
  87. Pevny L., Rao M.S. The stem cell menagerie. Trends Neurosci. 2003;26:351–359. doi: 10.1016/S0166-2236(03)00169-3. [DOI] [PubMed] [Google Scholar]
  88. Piacibello W., Sanavio F., Garetto L., et al. Extensive amplification and self-renewal of human haemopoietic stem cells from cord blood. Blood. 1997;89:2644–2653. [PubMed] [Google Scholar]
  89. Pittenger M.F., Mackay A.M., Beck S.C., et al. Multilineage potential of adult mesenchymal stem cells. Science. 1999;284:143–147. doi: 10.1126/science.284.5411.143. [DOI] [PubMed] [Google Scholar]
  90. Polakis P. WNT signaling and cancer. Genes Dev. 2000;14:1837–1851. [PubMed] [Google Scholar]
  91. Polesskaya A., Seale P., Rutnicki M.A. WNT signaling induces the myogenic specification of resident C45+ adult stem cells during muscle regeneration. Cell. 2003;113:841–852. doi: 10.1016/S0092-8674(03)00437-9. [DOI] [PubMed] [Google Scholar]
  92. Quesenberry P.J., Colvin G.A., Lambert J. The chiaroscuro stem cell: a unified stem cell theory. Blood. 2002;100:4266–4271. doi: 10.1182/blood-2002-04-1246. [DOI] [PubMed] [Google Scholar]
  93. Ramalho Santos M., Yoon S., Matzusaki Y., et al. Stemness: transcriptional profiling of embryonic and adult stem cells. Science. 2002;298:597–600. doi: 10.1126/science.1072530. [DOI] [PubMed] [Google Scholar]
  94. Reya T., Morrison S.J., Clarke M.F., Weissman I.L. Stem cells, cancer and cancer stem cells. Nature. 2002;414:105–111. doi: 10.1038/35102167. [DOI] [PubMed] [Google Scholar]
  95. Ringertz N.R., Savage R.E. Cell Hybrids. New York: Acad. Press; 1976. [Google Scholar]
  96. Roche E., Burcin M.M., et al. The use of gating technology in bioengineering insulin-secreting cells from embryonic stem cells. Cytotechnology. 2003;41:145–151. doi: 10.1023/A:1024878807264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Rosendaaal M., Hodson G.S., Bradley T.R. Organization of haemopoietic stem cells: the generation-age hypothesis. Cell Tissue Kinet. 1979;12:17–29. doi: 10.1111/j.1365-2184.1979.tb00110.x. [DOI] [PubMed] [Google Scholar]
  98. Rudnicki M.A. Marrow to musclefission versus fusion. Nat. Med. 2003;6:1461–1462. doi: 10.1038/nm1203-1461. [DOI] [PubMed] [Google Scholar]
  99. Sanchez-Ramos J.R. Neural cells derived from adult bone marrow and umbilical cord blood. J. Neurosci. Res. 2002;69:880–893. doi: 10.1002/jnr.10337. [DOI] [PubMed] [Google Scholar]
  100. Servida F., Soligo D., Caneva L., et al. Functional and morphological characterization of immunomagnetically selected CD34+ haemopoietic progenitor cells. Stem Cells. 1996;14:430–438. doi: 10.1002/stem.140430. [DOI] [PubMed] [Google Scholar]
  101. Sgaramella V. Theory and praxis of cloning via nuclear transfer. Cytotechnology. 2003;41:69–73. doi: 10.1023/A:1024814520468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Shamblott M.J., Axelman J., Littlefield J.W., et al. Human embryonic germ cell derivatives express a broad range of developmental distinct markers and proliferate extensively in vitro. Proc. Natl. Ac. Sci. USA. 2001;98:113–118. doi: 10.1073/pnas.021537998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Sharov A.A., Piao Y., Matoba R., et al. Transcriptome analysis of mouse stem cells and early embryos. PLOS Biol. 2004;1:410–419. doi: 10.1371/journal.pbio.0000074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Silva G.A., Czeisler C., Niece K.L., et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science. 2004;303:1352–1355. doi: 10.1126/science.1093783. [DOI] [PubMed] [Google Scholar]
  105. Singh S.K., Clarke J.D., Terasaki M., et al. Identification of a cancer stem cell in human brain tumours. Cancer Res. 2003;63:5821–5828. [PubMed] [Google Scholar]
  106. Slack J. Skinny dipping for stem cells. Nat. Cell Biol. 2001;3:205–206. doi: 10.1038/ncb0901-e205. [DOI] [PubMed] [Google Scholar]
  107. Sommer L., Rao M.S. Neural stem cells and regulation of cell number. Progr. Neurobiol. 2002;66:1–18. doi: 10.1016/S0301-0082(01)00022-3. [DOI] [PubMed] [Google Scholar]
  108. Tada M., Takayama Y., Abe K., et al. Nuclear reprogramming of somatic cells by in vitro hibridization with ES cells. Curr. Biol. 2001;11:1553–1558. doi: 10.1016/S0960-9822(01)00459-6. [DOI] [PubMed] [Google Scholar]
  109. Takagi N., Yoshida M.A., Sugawara O., Sasaki M. Reversal of X-inactivation in female mouse somatic cells hybridized with murine teratoma cells in vitro. Cell. 1983;34:1053–1062. doi: 10.1016/0092-8674(83)90563-9. [DOI] [PubMed] [Google Scholar]
  110. Terada N., Hamazaki T., Oka M., et al. Bone marrow cells adopt the phenotype of other cells by spontaneous fusion. Nature. 2002;416:542–545. doi: 10.1038/nature730. [DOI] [PubMed] [Google Scholar]
  111. Theise N.D. Liver stem cells. Cytotechnology. 2003;139:139–144. doi: 10.1023/A:1024826823194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Thomas E.D. Frontiers in bone marrow transplantation. Blood cells. 1991;17:259–267. [PubMed] [Google Scholar]
  113. Thomas E.D. A history of haemopoietic cell transplantation. Br. J. Haematol. 1999;105:330–339. doi: 10.1111/j.1365-2141.1999.01337.x. [DOI] [PubMed] [Google Scholar]
  114. Thompson A., Iskovitz-Eldor J., Shapiro S.S., et al. Embryonic stem cell line derived from human blastocysts. Science. 1998;282:1145–1147. doi: 10.1126/science.282.5391.1145. [DOI] [PubMed] [Google Scholar]
  115. To L.B., Haylock D.N., Dows T., et al. A comparative study of the phenotype and of proliferative capacity of peripheral blood CD34+ cells mobilized by four different protocols and those of steady phase PB and BM CD34+ cells. Blood. 1994;84:2930–2939. [PubMed] [Google Scholar]
  116. Toma J.G., Akhavan M., Fernandes K.J., et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat. Cell Biol. 2001;3:778–784. doi: 10.1038/ncb0901-778. [DOI] [PubMed] [Google Scholar]
  117. Tsai R., McKay R. A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Gen. Dev. 2002;16:2991–3003. doi: 10.1101/gad.55671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Van de Wetering M., Sancho E., Verweij C., et al. The beta-catenin/TC4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111:241–250. doi: 10.1016/S0092-8674(02)01014-0. [DOI] [PubMed] [Google Scholar]
  119. Van der Kooy D., Weiss S. Why stem cells? Science. 2000;287:1439–1444. doi: 10.1126/science.287.5457.1439. [DOI] [PubMed] [Google Scholar]
  120. Wagner J.E., Rosenthal J., Sweetman R., et al. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors. Blood. 1996;88:795–802. [PubMed] [Google Scholar]
  121. Watt F. Stem cells fate and patterning in mammalian epidermis. Curr. Opin. Gen. Dev. 2001;11:410–417. doi: 10.1016/S0959-437X(00)00211-2. [DOI] [PubMed] [Google Scholar]
  122. Weissman I.L. Stem cells: units of developmentunits of regeneration, and units of evolution. Cell. 2000;100:157–168. doi: 10.1016/S0092-8674(00)81692-X. [DOI] [PubMed] [Google Scholar]
  123. Weissman I.L. Stem cells. Scientific, medical and political issues. N. Engl. J. Med. 2002;346:1567–1579. doi: 10.1056/NEJMsb020693. [DOI] [PubMed] [Google Scholar]
  124. Ying O.L., Nichols J., Evans E.P., Smith A.G. Changing potency by spontaneous fusion. Nature. 2002;416:545–548. doi: 10.1038/nature729. [DOI] [PubMed] [Google Scholar]
  125. Zhang X.B., Li K., Fok T.F., et al. Cobblestone area-forming cells, long term culture initiating cells and NOD /SCID repopulating cells in human neonatal blood: a comparison with umbilical cord blood. Bone Marrow Transplant. 2002;30:557–564. doi: 10.1038/sj.bmt.1703714. [DOI] [PubMed] [Google Scholar]

Articles from Cytotechnology are provided here courtesy of Springer Science+Business Media B.V.

RESOURCES