Download PDF
Semin Reprod Med 2006; 24(5): 379-388
DOI: 10.1055/s-2006-952153
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Pluripotency in Adult Stem Cells: State of the Art

Marta Serafini1 , Catherine M. Verfaillie2
  • 1Stem Cell Institute, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota
  • 2Professor of Medicine, Director, Stamcel Instituut Leuven, Katholieke Universiteit Leuven, Leuven, Belgium
Further Information

Publication History

Publication Date:
22 November 2006 (online)

    Permissions and Reprints

ABSTRACT

For many years, it has long been known that stem cells derived from adult tissues maintain the capacity for self-renewal and differentiation into multiple cell types that are characteristic of the tissue of origin. Recent studies have shown new evidence that several tissues may contain cells capable of generating differentiated cells beyond their own tissue boundaries, defining a process termed stem cell plasticity. The pluripotency of adult stem cells have evoked significant excitement over the possibility of novel functional uses of stem cells, with the final purpose to develop new and more effective treatment strategies. However, despite the number of promising studies describing the plasticity of adult stem cells, many questions remain to be answered.

In this article, we critically review the current state of the art in the field of adult stem cells, focussing on the present understanding of the concepts of stem cell pluripotency and plasticity.

KEYWORDS

Stem cells - totipotency - pluripotency - multipotency - unipotency - plasticity

REFERENCES

  • 1 Evans M J, Kaufman M H. Establishment in culture of pluripotential cells from mouse embryos.  Nature. 1981;  292 154-156
    CrossrefPubMedGoogle Scholar
  • 2 Thomson J A, Itskovitz-Eldor J, Shapiro S S et al.. Embryonic stem cell lines derived from human blastocysts.  Science. 1998;  282 1145-1147
    CrossrefPubMedGoogle Scholar
  • 3 Thomson J, Kalishman J, Golos T et al.. 1995. Isolation of a primate embryonic stem cell line.  Proc Natl Acad Sci U S A. 1995;  92 7844-7848
    PubMedGoogle Scholar
  • 4 Shamblott M, Axelman J, Wang S et al.. Derivation of pluripotent stem cells from cultured human primordial germ cells.  Proc Natl Acad Sci USA. 1998;  95 13726-13731
    PubMedGoogle Scholar
  • 5 Nagy A, Rossant J, Nagy R, Abramow-Newerly W, Roder J C. Derivation of completely cell culture-derived mice from early-passage embryonic stem cells.  Proc Natl Acad Sci USA. 1993;  90 8424-8428
    CrossrefPubMedGoogle Scholar
  • 6 Smith A G. Embryo-derived stem cells: of mice and men.  Annu Rev Cell Dev Biol. 2000;  17 435-462
    PubMedGoogle Scholar
  • 7 Pera M F, Reubinoff B, Trounson A. Human embryonic stem cells.  J Cell Sci. 2000;  113 5-10
    PubMedGoogle Scholar
  • 8 Spangrude G, Heimfeld S, Weissman I. Purification and characterization of mouse hematopoietic stem cells.  Science. 1988;  241 58-62
    PubMedGoogle Scholar
  • 9 Osawa M, Hanada K, Hamada H, Nakauchi H. Long-term lymphohematopoietic reconstitution by a single 34-low/negative hematopoietic stem cell.  Science. 1996;  273 242-245
    PubMedGoogle Scholar
  • 10 Bhatia M, Bonnet D, Dick J E. Identification of a novel CD34 negative population of primitive human hematopoietic cells capabale of repopulating NOD/SCID mice.  Blood. 1997;  90 1134a
    PubMedGoogle Scholar
  • 11 Weissman I L, Anderson D J, Gage F. Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations.  Annu Rev Cell Dev Biol. 2001;  17 387-403
    CrossrefPubMedGoogle Scholar
  • 12 Stemple D L, Anderson D J. Isolation of a stem cell for neurons and glia from the mammalian neural crest.  Cell. 1992;  71 973-985
    CrossrefPubMedGoogle Scholar
  • 13 Rietze R L, Valcanis H, Brooker G F, Thomas T, Voss A K, Bartlett P F. Purification of a pluripotent neural stem cell from the adult mouse brain.  Nature. 2001;  412 736-739
    PubMedGoogle Scholar
  • 14 Seaberg R M, Smukler S R, Kieffer T J et al.. Clonal identification of multipotent precursors from adult mouse pancreas that generate neural and pancreatic lineages.  Nat Biotechnol. 2004;  22 1115-1124
    PubMedGoogle Scholar
  • 15 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
    CrossrefPubMedGoogle Scholar
  • 16 Jiang Y, Jahagirdar B, Reyes M et al.. Pluripotent nature of adult marrow derived mesenchymal stem cells.  Nature. 2002;  418 41-49
    CrossrefPubMedGoogle Scholar
  • 17 Kogler G, Sensken S, Airey J A et al.. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.  J Exp Med. 2004;  200 123-135
    CrossrefPubMedGoogle Scholar
  • 18 D'Ippolito G, Diabira S, Howard G A, Menei P, Roos B A, Schiller P C. 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 2971-2981
    CrossrefPubMedGoogle Scholar
  • 19 Yoon Y S, Wecker A, Heyd L et al.. Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction.  J Clin Invest. 2005;  115 326-338
    CrossrefPubMedGoogle Scholar
  • 20 Brook F A, Gardner R L. The origin and efficient derivation of embryonic stem cells in the mouse.  Proc Natl Acad Sci USA. 1997;  94 5709-5712
    CrossrefPubMedGoogle Scholar
  • 21 McKay R. Stem cells in the central nervous system.  Science. 1997;  276 66-71
    CrossrefPubMedGoogle Scholar
  • 22 Gage F H. Mammalian neural stem cells.  Science. 2000;  287 1433-1438
    CrossrefPubMedGoogle Scholar
  • 23 Watt F M. Stem cell fate and patterning in mammalian epidermis.  Curr Opin Genet Dev. 2001;  11 410-417
    CrossrefPubMedGoogle Scholar
  • 24 Daniels J T, Dart J K, Tuft S J, Khaw P T. Corneal stem cells in review.  Wound Repair Regen. 2001;  9 483-494
    CrossrefPubMedGoogle Scholar
  • 25 Slack J M. Developmental biology of the pancreas.  Development. 1995;  121 1569-1580
    PubMedGoogle Scholar
  • 26 Spradling A, Drummond-Barbosa D, Kai T. Stem cells find their niche.  Nature. 2001;  414 98-104
    PubMedGoogle Scholar
  • 27 Alonso L, Fuchs E. Stem cells of the skin epithelium.  Proc Natl Acad Sci USA. 2003;  100(suppl 1) 11830-11835
    CrossrefPubMedGoogle Scholar
  • 28 Blau H M, Brazelton T R, Weimann J M. The evolving concept of a stem cell: entity or function?.  Cell. 2001;  105 829-841
    CrossrefPubMedGoogle Scholar
  • 29 Mauro A. Satellite cell of skeletal muscle fibers.  J Biophys Biochem Cytol. 1961;  9 493-495
    CrossrefPubMedGoogle Scholar
  • 30 Holterman C E, Rudnicki M A. Molecular regulation of satellite cell function.  Semin Cell Dev Biol. 2000;  13(6) 439-446
    PubMedGoogle Scholar
  • 31 Rafii S, Shapiro F, Rimarachin J et al.. Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion.  Blood. 1994;  84 10-19
    PubMedGoogle Scholar
  • 32 Krause D S, Theise N D, Collector M I et al.. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell.  Cell. 2001;  105 369-377
    CrossrefPubMedGoogle Scholar
  • 33 Theise N D, Badve S, Saxena R et al.. Derivation of hepatocytes from bone marrow cells in mice after radiation-induced myeloablation.  Hepatology. 2000;  31 235-240
    CrossrefPubMedGoogle Scholar
  • 34 Kale S, Karihaloo A, Clark P R, Kashgarian M, Krause D S, Cantley L G. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule.  J Clin Invest. 2003;  112 42-49
    CrossrefPubMedGoogle Scholar
  • 35 Petersen B E, Bowen W C, Patrene K D et al.. Bone marrow as a potential source of hepatic oval cells.  Science. 1999;  284 1168-1170
    CrossrefPubMedGoogle Scholar
  • 36 Lagasse E, Connors H, Al-Dhalimy M et al.. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo .  Nat Med. 2000;  6 1229-1234
    CrossrefPubMedGoogle Scholar
  • 37 Vassilopoulos G, Wang P R, Russell D W. Transplanted bone marrow regenerates liver by cell fusion.  Nature. 2003;  422 901-904
    CrossrefPubMedGoogle Scholar
  • 38 Wang X, Willenbring H, Akkari Y et al.. Cell fusion is the principal source of bone-marrow-derived hepatocytes.  Nature. 2003;  422 897-901
    CrossrefPubMedGoogle Scholar
  • 39 Ianus A, Holz G G, Theise N D, Hussain M A. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion.  J Clin Invest. 2003;  111 843-850
    PubMedGoogle Scholar
  • 40 Wagers A J, Sherwood R I, Christensen J L, Weissman I L. Little evidence for developmental plasticity of adult hematopoietic stem cells.  Science. 2002;  297 2256-2259
    CrossrefPubMedGoogle Scholar
  • 41 Alvarez-Dolado M, Pardal R, Garcia-Verdugo J M et al.. Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes.  Nature. 2003;  425 968-973
    PubMedGoogle Scholar
  • 42 Brazelton T R, Rossi F MV, Keshet G I, Blau H M. From marrow to brain: expression of neuronal phenotypes in adult mice.  Science. 2000;  290 1775-1779
    CrossrefPubMedGoogle Scholar
  • 43 Mezey E, Chandross K J, Harta G, Maki R A, McKercher S R. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow.  Science. 2000;  290 1779-1782
    CrossrefPubMedGoogle Scholar
  • 44 Priller J, Persons D A, Klett F F, Kempermann G, Kreutzberg G W, Dirnagl U. Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo .  J Cell Biol. 2001;  155 733-738
    CrossrefPubMedGoogle Scholar
  • 45 Weimann J M, Charlton C A, Brazelton T R, Hackman R C, Blau H M. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains.  Proc Natl Acad Sci USA. 2003;  100 2088-2093
    CrossrefPubMedGoogle Scholar
  • 46 Weimann J M, Johansson C B, Trejo A, Blau H M. Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant.  Nat Cell Biol. 2003;  5 959-966
    CrossrefPubMedGoogle Scholar
  • 47 LaBarge M A, Blau H M. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury.  Cell. 2002;  111 589-601
    CrossrefPubMedGoogle Scholar
  • 48 Camargo F D, Green R, Capetenaki Y, Jackson K A, Goodell M A. Single hematopoietic stem cells generate skeletal muscle through myeloid intermediates.  Nat Med. 2003;  9 1520-1527
    PubMedGoogle Scholar
  • 49 Corbel S Y, Lee A, Yi L et al.. Contribution of hematopoietic stem cells to skeletal muscle.  Nat Med. 2003;  9 1528-1532
    PubMedGoogle Scholar
  • 50 Ferrari G, Cusella-De Angelis G, Coletta M et al.. Muscle regeneration by bone marrow-derived myogenic progenitors.  Science. 1998;  279 1528-1530
    CrossrefPubMedGoogle Scholar
  • 51 Gussoni E, Soneoka Y, Strickland C et al.. Dystrophin expression in the mdx mouse restored by stem cell transplantation.  Nature. 1999;  401 390-394
    CrossrefPubMedGoogle Scholar
  • 52 Grant M B, May W S, Caballero S et al.. Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization.  Nat Med. 2002;  8 607-612
    PubMedGoogle Scholar
  • 53 Jackson K, Majka S M, Wang H et al.. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells.  J Clin Invest. 2001;  107 1395-1402
    CrossrefPubMedGoogle Scholar
  • 54 Orlic D, Kajstura J, Chimenti S et al.. Bone marrow cells regenerate infarcted myocardium.  Nature. 2001;  410 701-705
    CrossrefPubMedGoogle Scholar
  • 55 Orlic D, Kajstura J, Chimenti S et al.. Mobilized bone marrow cells repair the infarcted heart, improving function and survival.  Proc Natl Acad Sci USA. 2001;  98 10344-10349
    CrossrefPubMedGoogle Scholar
  • 56 Kajstura J, Rota M, Whang B et al.. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion.  Circ Res. 2005;  96 127-137
    PubMedGoogle Scholar
  • 57 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
    CrossrefPubMedGoogle Scholar
  • 58 Balsam L B, Wagers A J, Christensen J L, Kofidis T, Weissman I L, Robbins R C. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.  Nature. 2004;  428 668-673
    CrossrefPubMedGoogle Scholar
  • 59 Pittenger M F, Mackay A M, Beck S C et al.. Multilineage potential of adult human mesenchymal stem cells.  Science. 1999;  284 143-147
    CrossrefPubMedGoogle Scholar
  • 60 Prockop D. Marrow stromal cells as stem cells for nonhematopoietic tissues.  Science. 1997;  276 71-74
    CrossrefPubMedGoogle Scholar
  • 61 Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie C M. Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells.  Blood. 2001;  98 2615-2625
    CrossrefPubMedGoogle Scholar
  • 62 Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie C M. Multipotent progenitor cells can be isolated from post-natal murine bone marrow, muscle and brain.  Exp Hematol. 2002;  30 896-904
    CrossrefPubMedGoogle Scholar
  • 63 Kues W A, Carnwath J W, Niemann H. From fibroblasts and stem cells: implications for cell therapies and somatic cloning.  Reprod Fertil Dev. 2005;  17 125-134
    CrossrefPubMedGoogle Scholar
  • 64 Baum C, Weissman I, Tsukamoto A, Buckle A, Peault B. Isolation of a candidate human hematopoietic stem cell population.  Proc Natl Acad Sci USA. 1992;  89 2804-2808
    CrossrefPubMedGoogle Scholar
  • 65 Krause D S, Ito T, Fackler M J et al.. Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells.  Blood. 1994;  84 691-701
    PubMedGoogle Scholar
  • 66 Uchida N, Combs J, Chen S, Zanjani E, Hoffman R, Tsukamoto A. Primitive human hematopoietic cells displaying differential efflux of the rhodamine 123 dye have distinct biological activities.  Blood. 1996;  88 1297-1305
    PubMedGoogle Scholar
  • 67 Morrison S J, Weissman I L. The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype.  Immunity. 1994;  1 661-673
    CrossrefPubMedGoogle Scholar
  • 68 Zijlmans J M, Visser J W, Kleiverda K, Kluin P M, Willemze R, Fibbe W E. Modification of rhodamine staining allows identification of hematopoietic stem cells with preferential short-term or long-term bone marrow-repopulating ability.  Proc Natl Acad Sci USA. 1995;  92 8901-8905
    CrossrefPubMedGoogle Scholar
  • 69 Li C L, Johnson G R. Rhodamine123 reveals heterogeneity within murine Lin-, Sca-1 + hemopoietic stem cells.  J Exp Med. 1992;  175 1443-1447
    CrossrefPubMedGoogle Scholar
  • 70 Goodell M, Rosenzweig M, Kim H et al.. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of 34 antigen exist in multiple species.  Nat Med. 1997;  3 1337-1345
    CrossrefPubMedGoogle Scholar
  • 71 Goodell M, Brose K, Paradis G, Conner A, Mulligan R. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo .  J Exp Med. 1996;  183 1797-1806
    CrossrefPubMedGoogle Scholar
  • 72 Zhou S, Schuetz J D, Bunting K D et al.. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype.  Nat Med. 2001;  7 1028-1034
    CrossrefPubMedGoogle Scholar
  • 73 Chaudhary P M, Roninson I B. Expression and activity of P-glycoprotein a multidrug efflux pump in human hematopoietic stem cells.  Cell. 1991;  66 85-94
    CrossrefPubMedGoogle Scholar
  • 74 Michallet M, Philip T, Philip I et al.. Transplantation with selected autologous peripheral blood CD34 + Thy1 + hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution.  Exp Hematol. 2000;  28 858-870
    CrossrefPubMedGoogle Scholar
  • 75 Kawashima I, Zanjani E, Almaida-Porada G, Flake A, Zeng H, Ogawa M. CD34 + human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells.  Blood. 1996;  87 4136-4142
    PubMedGoogle Scholar
  • 76 Camargo F D, Finegold M, Goodell M A. Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners.  J Clin Invest. 2004;  113 1266-1270
    CrossrefPubMedGoogle Scholar
  • 77 Altman J, Das G. Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions.  J Comp Neurol. 1966;  126 337-389
    PubMedGoogle Scholar
  • 78 Uchida N, Buck D W, He D et al.. Direct isolation of human central nervous system stem cells.  Proc Natl Acad Sci USA. 2000;  97 14720-14725
    CrossrefPubMedGoogle Scholar
  • 79 Reynolds B, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.  Science. 1992;  255 1707-1710
    CrossrefPubMedGoogle Scholar
  • 80 Gritti A, Parati E A, Cova L et al.. Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor.  J Neurosci. 1996;  16 1091-1100
    PubMedGoogle Scholar
  • 81 Lois C, Alvarez-Buylla A. Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia.  Proc Natl Acad Sci USA. 1993;  90 2074-2077
    CrossrefPubMedGoogle Scholar
  • 82 Chiasson B J, Tropepe V, Morshead C M, Van der Kooy D. Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential but only subependymal cells have stem cell characteristics.  J Neurosci. 1999;  19 4462-4473
    PubMedGoogle Scholar
  • 83 Palmer T D, Takahashi J, Gage F H. The adult rat hippocampus contains primordial neural stem cells.  Mol Cell Neurosci. 1997;  8 389-404
    CrossrefPubMedGoogle Scholar
  • 84 Richards L J, Kilpatrick T J, Bartlett P F. 1992. De novo generation of neuronal cells from the adult mouse brain.  Proc Natl Acad Sci USA. 1992;  89 8591-8595
    CrossrefPubMedGoogle Scholar
  • 85 Johansson C B, Momma S, Clarke D L, Risling M, Lendahl U, Frisen J. Identification of a neural stem cell in the adult mammalian central nervous system.  Cell. 1999;  96 25-34
    CrossrefPubMedGoogle Scholar
  • 86 Suhonen J, Peterson D, Ray J, Gage F. Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo .  Nature. 1996;  383 624-627
    PubMedGoogle Scholar
  • 87 Doetsch F, Caille I, Lim D A, Garcia-Verdugo J M, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain.  Cell. 1999;  97 703-716
    CrossrefPubMedGoogle Scholar
  • 88 Gould E, Reeves A J, Graziano M S, Gross C G. Neurogenesis in the neocortex of adult primates.  Science. 1999;  286 548-552
    CrossrefPubMedGoogle Scholar
  • 89 Shihabuddin L S, Horner P J, Ray J, Gage F H. Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus.  J Neurosci. 2000;  20 8727-8735
    PubMedGoogle Scholar
  • 90 Brustle O, Karram K, Huttner A et al.. Chimeric brains generated by intraventricular transplantation of fetal human brain cells into embryonic rats.  Nat Biotechnol. 1998;  16 1040-1044
    PubMedGoogle Scholar
  • 91 Modo M, Mellodew K, Cash D et al.. Mapping transplanted stem cell migration after a stroke: a serial, in vivo magnetic resonance imaging study.  Neuroimage. 2004;  21 311-317
    CrossrefPubMedGoogle Scholar
  • 92 Kim J H, Auerbach J M, Rodriguez-Gomez J A et al.. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease.  Nature. 2002;  418 50-56
    CrossrefPubMedGoogle Scholar
  • 93 Brustle O, Jones K, Learish R et al.. Embryonic stem cell-derived glial precursors: a source of myelinating transplants.  Science. 1999;  285 754-756
    CrossrefPubMedGoogle Scholar
  • 94 Bulte J W, Zhang S, van Gelderen P et al.. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination.  Proc Natl Acad Sci USA. 1999;  96 15256-15261
    CrossrefPubMedGoogle Scholar
  • 95 Jansen E M, Solberg L, Underhill S et al.. Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats.  Exp Neurol. 1997;  147 487-497
    CrossrefPubMedGoogle Scholar
  • 96 Shih C C, Weng Y, Mamelak A, LeBon T, Hu M C, Forman S. Identification of a candidate human neurohematopoietic stem-cell population.  Blood. 2001;  98 2412-2422
    CrossrefPubMedGoogle Scholar
  • 97 Bjornson C R, Rietze R, Reynolds B, Magli M, Vescovi A. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo .  Science. 1999;  283 534-537
    CrossrefPubMedGoogle Scholar
  • 98 Morshead C M, Benveniste P, Iscove N N. Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations.  Nat Med. 2002;  8 268-273
    PubMedGoogle Scholar
  • 99 Clarke D L, Johansson C B, Wilbertz J et al.. Generalized potential of adult neural stem cells.  Science. 2000;  288 1660-1663
    CrossrefPubMedGoogle Scholar
  • 100 Tajbakhsh S. Skeletal muscle stem and progenitor cells: reconciling genetics and lineage.  Exp Cell Res. 2005;  306 364-372
    CrossrefPubMedGoogle Scholar
  • 101 Goldring K, Partridge T, Watt D. Muscle stem cells.  J Pathol. 2002;  197 457-467
    PubMedGoogle Scholar
  • 102 Seale P, Sabourin L A, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki M A. Pax7 is required for the specification of myogenic satellite cells.  Cell. 2000;  102 777-786
    CrossrefPubMedGoogle Scholar
  • 103 Asakura A, Komaki M, Rudnicki M. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation.  Differentiation. 2001;  68 245-253
    CrossrefPubMedGoogle Scholar
  • 104 Wada M R, Inagawa-Ogashiwa M, Shimizu S, Yasumoto S, Hashimoto N. Generation of different fates from multipotent muscle stem cells.  Development. 2002;  129 2987-2995
    PubMedGoogle Scholar
  • 105 Jackson K, Mi T, Goodell M A. Hematopoietic potential of stem cells isolated from murine skeletal muscle.  Proc Natl Acad Sci USA. 1999;  96 14482-14486
    CrossrefPubMedGoogle Scholar
  • 106 McKinney-Freeman S L, Jackson K A, Camargo F D, Ferrari G, Mavilio F, Goodell M A. Muscle-derived hematopoietic stem cells are hematopoietic in origin.  Proc Natl Acad Sci USA. 2002;  99 1341-1346
    CrossrefPubMedGoogle Scholar
  • 107 Kawada H, Ogawa M. Bone marrow origin of hematopoietic progenitors and stem cells in murine muscle.  Blood. 2001;  98 2008-2013
    CrossrefPubMedGoogle Scholar
  • 108 Fridenshtein A. Stromal bone marrow cells and the hematopoietic microenvironment.  Arkh Patol. 1982;  44 3-11
    PubMedGoogle Scholar
  • 109 De Ugarte D A, Morizono K, Elbarbary A et al.. Comparison of multi-lineage cells from human adipose tissue and bone marrow.  Cells Tissues Organs. 2003;  174 101-109
    CrossrefPubMedGoogle Scholar
  • 110 Campagnoli C, Roberts I A, Kumar S, Bennett P R, Bellantuono I, Fisk N M. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow.  Blood. 2001;  98 2396-2402
    CrossrefPubMedGoogle Scholar
  • 111 Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K. Human placenta-derived cells have mesenchymal stem/progenitor cell potential.  Stem Cells. 2004;  22 649-658
    CrossrefPubMedGoogle Scholar
  • 112 Miura M, Gronthos S, Zhao M et al.. SHED: stem cells from human exfoliated deciduous teeth.  Proc Natl Acad Sci USA. 2003;  100 5807-5812
    CrossrefPubMedGoogle Scholar
  • 113 Wakitani S, Saito T, Caplan A. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine.  Muscle Nerve. 1995;  18 1417-1426
    CrossrefPubMedGoogle Scholar
  • 114 Gronthos S, Zannettino A C, Hay S J et al.. Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow.  J Cell Sci. 2003;  116 1827-1835
    CrossrefPubMedGoogle Scholar
  • 115 Colter D C, Class R, DiGirolamo C M, Prockop D J. Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow.  Proc Natl Acad Sci USA. 2000;  97 3213-3218
    CrossrefPubMedGoogle Scholar
  • 116 Pereira R F, O'Hara M D, Laptev A V et al.. Marrow stromal cells as a source of progenitor cells for nonhematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta.  Proc Natl Acad Sci USA. 1998;  95 1142-1147
    CrossrefPubMedGoogle Scholar
  • 117 Liechty K W, MacKenzie T C, Shaaban A F et al.. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep.  Nat Med. 2000;  6 1282-1286
    CrossrefPubMedGoogle Scholar
  • 118 Sanchez-Ramos J, Song S, Cardozo-Pelaez F et al.. Adult bone marrow stromal cells differentiate into neural cells in vitro .  Exp Neurol. 2000;  164 247-256
    CrossrefPubMedGoogle Scholar
  • 119 Woodbury D, Schwarz E J, Prockop D J, Black I B. Adult rat and human bone marrow stromal cells differentiate into neurons.  J Neurosci Res. 2000;  61 364-370
    CrossrefPubMedGoogle Scholar
  • 120 Zhao L R, Duan W M, Reyes M, Keene C D, Verfaillie C M, Low W C. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats.  Exp Neurol. 2002;  174 11-20
    CrossrefPubMedGoogle Scholar
  • 121 Kopen G, Prockop D, Phinney D. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains.  Proc Natl Acad Sci USA. 1999;  96 10711-10716
    CrossrefPubMedGoogle Scholar
  • 122 Jin H K, Carter J E, Huntley G W, Schuchman E H. Intracerebral transplantation of mesenchymal stem cells into acid sphingomyelinase-deficient mice delays the onset of neurological abnormalities and extends their life span.  J Clin Invest. 2002;  109 1183-1191
    CrossrefPubMedGoogle Scholar
  • 123 Akiyama Y, Radtke C, Kocsis J D. Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells.  J Neurosci. 2002;  22 6623-6630
    PubMedGoogle Scholar
  • 124 Horwitz E M, Prockop D J, Fitzpatrick L A et al.. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta.  Nat Med. 1999;  5 309-315
    CrossrefPubMedGoogle Scholar
  • 125 Koc O N, Day J, Nieder M, Gerson S L, Lazarus H M, Krivit W. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH).  Bone Marrow Transplant. 2002;  30 215-222
    CrossrefPubMedGoogle Scholar
  • 126 Scholer H R, Hatzopoulos A K, Balling R, Suzuki N, Gruss P. A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor.  EMBO J. 1989;  8 2543-2550
    PubMedGoogle Scholar
  • 127 Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker P H, Verfaillie C M. Origin of endothelial progenitors in human postnatal bone marrow.  J Clin Invest. 2002;  109 337-346
    CrossrefPubMedGoogle Scholar
  • 128 Schwartz R E, Reyes M, Koodie L et al.. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells.  J Clin Invest. 2002;  109 1291-1302
    CrossrefPubMedGoogle Scholar
  • 129 Jiang Y, Blackstad M, Chen A, Miller R F, Verfaillie C M. Neuroectodermal differentiation from mouse multipotent adult progenitor cells.  Proc Natl Acad Sci USA. 2003;  100(suppl 1) 11854-11860
    CrossrefPubMedGoogle Scholar
  • 130 Keene C D, Ortiz-Gonzalez X R, Jiang Y, Largaespada D A, Verfaillie C M, Low W C. Neural differentiation and incorporation of bone marrow-derived multipotent adult progenitor cells after single cell transplantation into blastocyst stage mouse embryos.  Cell Transplant. 2003;  12 210-213
    PubMedGoogle Scholar
  • 131 Reyes M, Li S, Foraker J, Kimura E, Chamberlain J S. Donor origin of multipotent adult progenitor cells in radiation chimeras.  Blood. 2005;  106 3646-3649
    CrossrefPubMedGoogle Scholar
  • 132 Toma J G, McKenzie I A, Bagli D, Miller F D. Isolation and characterization of multipotent skin-derived precursors from human skin.  Stem Cells. 2005;  23 727-737
    CrossrefPubMedGoogle Scholar
  • 133 Fernandes K J, McKenzie I A, Mill P et al.. A dermal niche for multipotent adult skin-derived precursor cells.  Nat Cell Biol. 2004;  6 1082-1093
    CrossrefPubMedGoogle Scholar

Marta Serafini

Stem Cell Institute, Department of Medicine, University of Minnesota Medical School, Minneapolis

MN 55455

Email: serafini@marionegri.it