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Mesenchymal Stem Cells: An Oversimplified Nomenclature for Extremely Heterogeneous Progenitors

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Regenerative Medicine

Abstract

Mesenchymal stem cells (MSC) are plastic-adherent fibroblast-like cells that can readily be isolated from various tissues and expanded in vitro. Per definitionem, they are able to differentiate into bone, cartilage and adipose ­tissue. Different preparative protocols have been shown to yield MSC-like cell lines from starting materials as diverse as bone marrow, fat tissue, umbilical cord blood and peripheral blood. However, MSC are still ill-defined by physical, phenotypic and functional properties. Furthermore, the composition of cell preparations and the differentiation potential changes in the course of long-term culture expansion. There is an urgent need for the development of molecular markers and universal criteria for quality control of the starting cell populations as well as for the cell products after expansion. Nevertheless, MSC have already found their way into a vast number of clinical studies addressing a broad variety of diseases. Even though there is no convincing evidence that MSC are involved in the process of tissue repair by transdifferentiation, they probably contribute to the repair process by immunomodulatory effects and interaction with other cell types.

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References

  • Aksu AE, Horibe E, Sacks J, Ikeguchi R, Breitinger J, Scozio M, Unadkat J, Feili-Hariri M (2008) Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and ­promotes vascularized skin allograft survival in rats. Clin Immunol. 127(3):348–58.

    CAS  PubMed  Google Scholar 

  • Anderson DG, Levenberg S, Langer R (2004) Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotechnol. 22:863–6.

    CAS  PubMed  Google Scholar 

  • Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ and Bellantuono I (2004) Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22, 675–682.

    CAS  PubMed  Google Scholar 

  • Bieback K, Kern S, Kluter H et al. (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 22:625–34.

    PubMed  Google Scholar 

  • Bieback K, Hecker A, Kocaömer A, Lannert H, Schallmoser K, Strunk D, Klüter H (2009) Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells. 27(9):2331–41.

    CAS  PubMed  Google Scholar 

  • Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, and Nikbin B (2006). Aging of mesenchymal stem cell in vitro. BMC. Cell Biol. 7, 14.

    PubMed  Google Scholar 

  • Bork S, Pfister S, Witt H, Horn P, Korn B, Ho AD, Wagner W (2009) DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells. Aging Cell. 2009 Nov 6. (Epub ahead of print)

    Google Scholar 

  • Buhring HJ, Battula VL, Treml S et al. (2007) Novel markers for the prospective isolation of human MSC. Ann NY Acad Sci. 1106:262–271.

    PubMed  Google Scholar 

  • Caplan AI (1991) Mesenchymal stem cells. J Orthop Res. 9:641–50.

    CAS  PubMed  Google Scholar 

  • Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem. 98:1076–84.

    CAS  PubMed  Google Scholar 

  • Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA and Goodell MA (2007). Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol. 5, 201.

    Google Scholar 

  • Check E (2007) The hard copy. News feature. Nature. 446: 485–486.

    CAS  PubMed  Google Scholar 

  • Colter DC, Sekiya I, Prockop DJ (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci USA. 98:7841–5.

    CAS  PubMed  Google Scholar 

  • Cristofalo VJ, Allen RG, Pignolo RJ, Martin BG and Beck JC (1998) Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc. Natl. Acad. Sci. 95, 10614–10619.

    CAS  PubMed  Google Scholar 

  • da Silva ML, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 119:2204–13.

    Google Scholar 

  • Di Donna S, Mamchaoui K, Cooper RN, Seigneurin-Venin S, Tremblay J, Butler-Browne GS, and Mouly V (2003) Telomerase can extend the proliferative capacity of human myoblasts, but does not lead to their immortalization. Mol Cancer Res. 1, 643–653.

    PubMed  Google Scholar 

  • DiGirolamo CM, Stokes D, Colter D et al. (1999) Propagation and senescence of human marrow stromal cells in culture: a simple colony-forming assay identifies samples with the greatest potential to propagate and differentiate. Br J Haematol. 107:275–81.

    CAS  PubMed  Google Scholar 

  • Dominici M, Le Blanc K, Mueller I et al. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8:315–7.

    CAS  PubMed  Google Scholar 

  • Engler AJ, Sen S, Sweeney HL et al. (2006) Matrix elasticity directs stem cell lineage specification. Cell. 126:677–89.

    CAS  PubMed  Google Scholar 

  • Erices A, Conget P, Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 109:235–42.

    CAS  PubMed  Google Scholar 

  • Fehrer C and Lepperdinger G (2005). Mesenchymal stem cell aging. Exp Gerontol. 40, 926–930.

    CAS  PubMed  Google Scholar 

  • Fehrer C, Laschober G, Lepperdinger G (2006) Aging of murine mesenchymal stem cells. Ann N Y Acad Sci. 1067:235–42

    CAS  PubMed  Google Scholar 

  • Franke WW, Grund C, Jackson BW et al. (1983) Formation of cytoskeletal elements during mouse embryogenesis. IV. Ultrastructure of primary mesenchymal cells and their cell-cell interactions. Differentiation. 25:121–41.

    CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 16:381–90.

    CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Petrakova KV, Kurolesova AI et al. (1968) Heterotopic of bone marrow.Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 6:230–47.

    CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Chailakhyan RK, Latsinik NV et al. (1974) Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 17:331–40.

    CAS  PubMed  Google Scholar 

  • Grinnemo KH, Månsson-Broberg A, Leblanc K, Corbascio M, Wärdell E, Siddiqui AJ, Hao X, Sylvén C, Dellgren G (2006) Human mesenchymal stem cells do not differentiate into cardiomyocytes in a cardiac ischemic xenomodel. Ann Med. 38: 144–53.

    CAS  PubMed  Google Scholar 

  • Halasa M, Baskiewicz-Masiuk M, Dabkowska E et al. (2008) An efficient two-step method to purify very small embryonic-like (VSEL) stem cells from umbilical cord blood (UCB). Folia Histochem Cytobiol. 46(2):239–43.

    PubMed  Google Scholar 

  • Hayflick, L (1965) The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37, 614–636.

    CAS  PubMed  Google Scholar 

  • Ho AD, Wagner W and Mahlknecht U (2005) Stem cells and ageing. The potential of stem cells to overcome age-related deteriorations of the body in regenerative medicine. EMBO Rep. 6, 35–38.

    Google Scholar 

  • Ho AD, Wagner W and Franke WW (2008). Heterogeneity of mesenchymal stromal cell preparations. Cytotherapy 10, 320–330.

    CAS  PubMed  Google Scholar 

  • Horn P, Bork S, Diehlmann A, Walenda T, Eckstein V, Ho AD, Wagner W (2008) Isolation of human mesenchymal stromal cells is more efficient by red blood cell lysis. Cytotherapy. 2008;10(7):676–85.

    CAS  PubMed  Google Scholar 

  • Horwitz EM and Keating A (2000) Nonhematopoietic mesenchymal stem cells: what are they? Cytotherapy. 2:387–8.

    CAS  PubMed  Google Scholar 

  • Horwitz EM, Le BK, Dominici M et al. (2005) Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 7:393–5.

    CAS  PubMed  Google Scholar 

  • Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE and Scadden DT (2006). Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443, 421–426.

    CAS  PubMed  Google Scholar 

  • Javazon EH, Beggs KJ, Flake AW (2004) Mesenchymal stem cells: paradoxes of passaging. Exp Hematol. 32:414–25.

    CAS  PubMed  Google Scholar 

  • Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002a) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 418:41–9.

    CAS  PubMed  Google Scholar 

  • Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM (2002b) Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol. 30:896–904.

    CAS  PubMed  Google Scholar 

  • Jiang Y, Henderson D, Blackstad M, Chen A, Miller RF, Verfaillie CM (2003) Neuroectodermal differentiation from mouse multipotent adult progenitor cells. Proc Natl Acad Sci USA. 100(Suppl 1):11854–60.

    CAS  PubMed  Google Scholar 

  • Johnstone B, Hering TM, Caplan AI et al. (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 238:265–72.

    CAS  PubMed  Google Scholar 

  • Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 4;449(7162):557–63.

    CAS  PubMed  Google Scholar 

  • Kern S, Eichler H, Stoeve J et al. (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 24:1294–301.

    CAS  PubMed  Google Scholar 

  • Kiyono T, Foster SA, Koop JI, McDougall JK, Galloway DA and Klingelhutz AJ (1998) Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature 396, 84–88.

    CAS  PubMed  Google Scholar 

  • Kocaoemer A, Kern S, Kluter H et al. (2007) Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue. Stem Cells. 25:1270–8.

    CAS  PubMed  Google Scholar 

  • Kogler G, Sensken S, Airey JA et al. (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med. 200:123–35.

    PubMed  Google Scholar 

  • Kotobuki N, Hirose M, Machida H et al. (2005) Viability and osteogenic potential of cryopreserved human bone marrow-derived mesenchymal cells. Tissue Eng. 11:663–73.

    CAS  PubMed  Google Scholar 

  • Kucia M, Reca R, Campbell FR et al. (2006a) A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia. 20(5):857–69.

    CAS  PubMed  Google Scholar 

  • Kucia M, Zuba-Surma E, Wysoczynski M et al. (2006b) Physiological and pathological consequences of identification of very small embryonic like (VSEL) stem cells in adult bone marrow. J Physiol Pharmacol. 57 Suppl 5:5–18.

    Google Scholar 

  • Kucia M, Wysoczynski M, Ratajczak J et al. (2008a) Identification of very small embryonic like (VSEL) stem cells in bone marrow. Cell Tissue Res. 331(1):125–34. Epub 2007 Sep 9. Review.

    CAS  PubMed  Google Scholar 

  • Kucia M, Wysoczynski M, Wu W et al. (2008b) Evidence that very small embryonic-like stem cells are mobilized into peripheral blood. Stem Cells. 26(8):2083–92. Epub 2008 May 29.

    CAS  PubMed  Google Scholar 

  • Kuznetsov SA, Mankani MH, Gronthos S et al. (2001) Circulating skeletal stem cells. J Cell Biol. 153:1133–40.

    CAS  PubMed  Google Scholar 

  • Lange C, Cakiroglu F, Spiess AN et al. (2007) Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. J Cell Physiol. 213(1):18–26.

    CAS  PubMed  Google Scholar 

  • Lansdorp PM (2008). Telomeres, stem cells, and hematology. Blood 111, 1759–1766.

    CAS  PubMed  Google Scholar 

  • Li Q, Hisha H, Takaki T, Adachi Y, Li M, Song C, Feng W, Okazaki S, Mizokami T, Kato J, Inaba M, Hosaka N, Maki M, Ikehara S. (2009) Transformation potential of bone marrow stromal cells into undifferentiated high-grade pleomorphic sarcoma. J Cancer Res Clin Oncol. Nov 21. (Epub ahead of print)

    Google Scholar 

  • Le Blanc K (2006) Mesenchymal stromal cells: Tissue repair and immune modulation. Cytotherapy 8(6):559–61.

    PubMed  Google Scholar 

  • Le Blanc K, Ringdén O. (2007a) Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 262(5):509–25.

    PubMed  Google Scholar 

  • Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, Ljungman P, Lönnies H, Nava S, Ringdén O. (2007b) Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia. 21(8):1733–8.

    PubMed  Google Scholar 

  • Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. May 10;371(9624):1579–86.

    PubMed  Google Scholar 

  • Mareschi K, Ferrero I, Rustichelli D, Aschero S, Gammaitoni L, Aglietta M, Madon E and Fagioli F (2006) Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow. J Cell Biochem. 97, 744–754.

    CAS  PubMed  Google Scholar 

  • Mazhari R and Hare JM (2007) Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat Clin Pract Cardiovasc Med. 4(Suppl 1): S21–6.

    PubMed  Google Scholar 

  • Masutomi K, Yu EY, Khurts S, Ben-Porath I, Currier JL, Metz GB, Brooks MW, Kaneko S, Murakami S, DeCaprio JA, Weinberg RA, Stewart SA and Hahn WC (2003). Telomerase maintains telomere structure in normal human cells. Cell 114, 241–253.

    CAS  PubMed  Google Scholar 

  • Meza-Zepeda LA, Noer A, Dahl JA, Micci F, Myklebost O and Collas P (2008). High-resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence. J Cell Mol. Med. 12, 553–563.

    CAS  PubMed  Google Scholar 

  • Morshead CM, Benveniste P, Iscove NN et al. (2002) Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat Med. 8:268–73.

    CAS  PubMed  Google Scholar 

  • Müller I, Kordowich S, Holzwarth C, Spano C, Isensee G, Staiber A, Viebahn S, Gieseke F, Langer H, Gawaz MP, Horwitz EM, Conte P, Handgretinger R, Dominici M (2006) Animal serum-free culture conditions for isolation and expansion of multipotent mesenchymal stromal cells from human BM. Cytotherapy. 8:437–44.

    PubMed  Google Scholar 

  • Müller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F, Dominici M, Greil J, Handgretinger R (2008a) Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis. 40(1):25–32.

    PubMed  Google Scholar 

  • Müller I, Vaegler M, Holzwarth C, Tzaribatchev N, Pfister SM, Schütt B, Reize P, Greil J, Handgretinger R, Rudert M (2008b) Secretion of angiogenic proteins by human multipotent mesenchymal stromal cells and their clinical potential in the treatment of avascular osteonecrosis. Leukemia. 22(11):2054–61.

    PubMed  Google Scholar 

  • Nakahara H, Bruder SP, Haynesworth SE et al. (1990) Bone and cartilage formation in diffusion chambers by subcultured cells derived from the periosteum. Bone. 11:181–8.

    CAS  PubMed  Google Scholar 

  • Nilsson O, Mitchum RD Jr, Schrier L, Ferns SP, Barnes KM, Troendle JF and Baron J (2005) Growth plate senescence is associated with loss of DNA methylation. J. Endocrinol. 186, 241–249.

    CAS  PubMed  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC et al. (1999) Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–7.

    CAS  PubMed  Google Scholar 

  • Quirici N, Soligo D, Bossolasco P et al. (2002) Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp Hematol. 30:783–91.

    CAS  PubMed  Google Scholar 

  • Raedt R, Pinxteren J, Van Dycke A et al. (2007) Differentiation assays of bone marrow-derived multipotent adult progenitor cell (MAPC)-like cells towards neural cells cannot depend on morphology and a limited set of neural markers. Exp Neurol. 203:542–54.

    CAS  PubMed  Google Scholar 

  • Ren H, Cao Y, Zhao Q et al. (2006) Proliferation and differentiation of bone marrow stromal cells under hypoxic conditions. Biochem Biophys Res Commun. 347:12–21.

    CAS  PubMed  Google Scholar 

  • Reyes M, Lund T, Lenvik T et al. (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood. 98:2615–25.

    CAS  PubMed  Google Scholar 

  • Roobrouck VD, Ulloa-Montoya F and Verfaillie CM (2008) Self-renewal and differentiation capacity of young and aged stem cells. Exp Cell Res. 314, 1937–1944.

    CAS  PubMed  Google Scholar 

  • Rosland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, Mysliwietz J, Tonn JC, Goldbrunner R, Lonning PE, Bjerkvig R and Schichor C (2009). Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res. 69, 5331–5339.

    CAS  PubMed  Google Scholar 

  • Rubio D, Garcia-Castro J, Martin MC de la FR, Cigudosa JC, Lloyd AC and Bernad A (2005) Spontaneous human adult stem cell transformation. Cancer Res. 65, 3035–3039.

    CAS  PubMed  Google Scholar 

  • Sabatini F, Petecchia L, Tavian M et al. (2005) Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest. 85: 962–71.

    CAS  PubMed  Google Scholar 

  • Schallmoser K, Bartmann C, Rohde E, Reinisch A, Kashofer K, Stadelmeyer E, Drexler C, Lanzer G, Linkesch W, Strunk D (2007) Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion. 47(8):1436–46.

    CAS  PubMed  Google Scholar 

  • Schallmoser K, Bartmann C, Rodhe E, Bork S, Guelly C, Obenauf AC, Reinisch A, Horn P, Ho AD, Strunk D, Wagner W. (2009) Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions. Haematologica, in print.

    Google Scholar 

  • Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM (2002) Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest. 109:1291–302.

    CAS  PubMed  Google Scholar 

  • Schneider EL and Mitsui Y (1976). The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci USA. 73, 3584–3588.

    CAS  PubMed  Google Scholar 

  • Serafini M, Dylla SJ, Oki M et al. (2007) Hematopoietic reconstitution by multipotent adult ­progenitor cells: precursors to long-term hematopoietic stem cells. J Exp Med. 204:129–39.

    CAS  PubMed  Google Scholar 

  • Shibata KR, Aoyama T, Shima Y, Fukiage K, Otsuka S, Furu M, Kohno Y, Ito K, Fujibayashi S, Neo M, Nakayama T, Nakamura T and Toguchida J (2007). Expression of the p16INK4A gene is associated closely with senescence of human mesenchymal stem cells and is potentially silenced by DNA methylation during in vitro expansion. Stem Cells 25, 2371–2382.

    CAS  PubMed  Google Scholar 

  • Simmons PJ and Torok-Storb B (1991) Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood. 78:55–62.

    CAS  PubMed  Google Scholar 

  • Sotiropoulou PA, Perez SA, Salagianni M et al. (2005) Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells.

    Google Scholar 

  • Stamm C, Liebold A, Steinhoff G et al. (2006) Stem cell therapy for ischemic heart disease: beginning or end of the road? Cell Transplant. 15(Suppl 1):S47–56.

    PubMed  Google Scholar 

  • Stenderup K, Justesen J, Clausen C and Kassem M (2003). Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33, 919–926.

    PubMed  Google Scholar 

  • Stolzing A, Jones E, McGonagle D and Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 129, 163–173.

    CAS  PubMed  Google Scholar 

  • Stute N, Holtz K, Bubenheim M et al. (2004) Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use. Exp Hematol. 32:1212–25.

    CAS  PubMed  Google Scholar 

  • Suzuki T, Farrar JE, Yegnasubramanian S, Zahed M, Suzuki N and Arceci RJ (2008). Stable knockdown of PASG enhances DNA demethylation but does not accelerate cellular senescence in TIG-7 human fibroblasts. Epigenetics. 3, 281–291.

    PubMed  Google Scholar 

  • Terada N, Hamazaki T, Oka M et al. (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature. 416:542–5.

    CAS  PubMed  Google Scholar 

  • Tian Y, Deng YB, Huang YJ, Wang Y (2008) Bone marrow-derived mesenchymal stem cells decrease acute graft-versus-host disease after allogeneic hematopoietic stem cells transplantation. Immunol Invest. 37(1):29–42.

    CAS  PubMed  Google Scholar 

  • Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 25(2):371–9.

    CAS  PubMed  Google Scholar 

  • Wagner W, Wein F, Seckinger A et al. (2005a) Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol. 33:1402–16.

    CAS  PubMed  Google Scholar 

  • Wagner W, Saffrich R, Wirkner U et al. (2005b) Hematopoietic progenitor cells and cellular microenvironment: behavioral and molecular changes upon interaction. Stem Cells. 23:1180–91.

    CAS  PubMed  Google Scholar 

  • Wagner W, Feldmann RE Jr, Seckinger A, Maurer MH, Wein F, Blake J, Krause U, Kalenka A, Burgers HF, Saffrich R, Wuchter P, Kuschinsky W, Ho AD (2006) The heterogeneity of human mesenchymal stem cell preparations – Evidence from simultaneous analysis of proteomes and transcriptomes. Exp Hematol. 34:536–48.

    CAS  PubMed  Google Scholar 

  • Wagner W and Ho AD (2007) Mesenchymal stem cell preparations – comparing apples and oranges. Stem Cell Rev 3, 239–248.

    PubMed  Google Scholar 

  • Wagner W, Roderburg C, Wein F et al. (2007a) Molecular and Secretory Profiles of Human Mesenchymal Stromal Cells and their Abilities to Maintain Primitive Hematopoietic Progenitors. Stem Cells. 10:2638–2647.

    Google Scholar 

  • Wagner W, Wein F, Roderburg C et al. (2007b) Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell-cell interaction. Exp Hematol. 35:314–25.

    CAS  PubMed  Google Scholar 

  • Wagner W, Wein F, Roderburg C et al. (2007c) Adhesion of human hematopoietic progenitor cells to mesenchymal stromal cells involves CD44. Cells Tissues Organs. 188(1–2):160–9.

    PubMed  Google Scholar 

  • Wagner, W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V and Ho AD (2008). Replicative Senescence of Mesenchymal Stem Cells – a Continuous and Organized Process. PLoS ONE 5, e2213.

    Google Scholar 

  • Wagner W, Bork S, Horn P, Krunic D, Walenda T, Diehlmann A, Benes V, Blake J, Huber FX, Eckstein V, Boukamp P and Ho AD (2009). Aging and replicative senescence have related effects on human stem and progenitor cells. PLoS ONE 4, e5846.

    PubMed  Google Scholar 

  • Walenda T, Bork S, Horn P, Wein F, Saffrich R, Diehlmann A, Eckstein V, Ho AD and Wagner W (2010). Co-Culture with Mesenchymal Stromal Cells Increases Proliferation and Maintenance of Hematopoietic Progenitor Cells. J Cell Mol Med. 14(1–2):337–50.

    Google Scholar 

  • Wang H and Scott RE (1993) Inhibition of distinct steps in the adipocyte differentiation pathway in 3 T3 T mesenchymal stem cells by dimethyl sulphoxide (DMSO). Cell Prolif. 26:55–66.

    CAS  PubMed  Google Scholar 

  • Wilson VL and Jones PA (1983) DNA methylation decreases in aging but not in immortal cells. Science 220, 1055–1057.

    CAS  PubMed  Google Scholar 

  • Wuchter P, Boda-Heggemann J, Straub BK, Grund C, Kuhn C, Krause U, Seckinger A, Peitsch WK, Spring H, Ho AD and Franke WW (2007) Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells. Cell Tissue Res. 328:499–514.

    PubMed  Google Scholar 

  • Wuchter P, Saffrich R, Wagner W, Wein F, Schubert M, Eckstein V and Ho AD (2008) Human hematopoietic stem cells and leukemic cells form cadherin-catenin based junctional complexes with mesenchymal stromal cells. Blood (ASH Annual Meeting Abstracts), 112:1367.

    Google Scholar 

  • Wuchter P, Saffrich R, Ludwig A, Schubert M, Eckstein V and Ho AD (2009) Cellular interaction between human mesenchymal stem cells and hematopoietic stem cells in 2D- and 3D-culture-systems. Blood (ASH Annual Meeting Abstracts), 114:1442.

    Google Scholar 

  • Ying QL, Nichols J, Evans EP et al. (2002) Changing potency by spontaneous fusion. Nature. 416:545–8.

    CAS  PubMed  Google Scholar 

  • Young JI and Smith JR (2001). DNA methyltransferase inhibition in normal human fibroblasts induces a p21-dependent cell cycle withdrawal. J Biol Chem. 276, 19610–19616.

    CAS  PubMed  Google Scholar 

  • Zeng L, Rahrmann E, Hu Q et al. (2006) Multipotent adult progenitor cells from swine bone marrow. Stem Cells. 24:2355–66.

    CAS  PubMed  Google Scholar 

  • Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, Leboff MS and Glowacki J (2008) Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell 7, 335–343.

    CAS  PubMed  Google Scholar 

  • Zimmermann S, Glaser S, Ketteler R, Waller CF, Klingmuller U and Martens UM (2004). Effects of telomerase modulation in human hematopoietic progenitor cells. Stem Cells 22, 741–749.

    CAS  PubMed  Google Scholar 

  • Zuk PA, Zhu M, Mizuno H et al. (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7:211–28.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the German Ministry of Education and Research (BMBF) within the supporting program “cell based regenerative medicine” (START-MSC2 and CB-HERMES), the German Research Foundation DFG (HO 914/7-1), the Network for Aging Research (NAR, Heidelberg), the Heidelberg Academy of Sciences (WIN-Kolleg) and the Stem Cell Network North Rhine Westphalia. We would like to thank Dr. Rainer Saffrich for excellent image acquisition.

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  1. Department of Medicine V, Heidelberg University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Patrick Wuchter & Anthony D. Ho

  2. Helmholtz-Institute for Biomedical Engineering, Cell Biology, University of Aachen Medical School, Pauwelsstrasse 20, 52074, Aachen, Germany

    Wolfgang Wagner

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  1. Patrick Wuchter
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  2. Wolfgang Wagner
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  3. Anthony D. Ho
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Correspondence to Anthony D. Ho .

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  1. Klinik und Poliklinik für Herzchirurgie, Universitätsklinikum Rostock, Schillingallee 35, Rostock, 18057, Germany

    Gustav Steinhoff

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Wuchter, P., Wagner, W., Ho, A.D. (2011). Mesenchymal Stem Cells: An Oversimplified Nomenclature for Extremely Heterogeneous Progenitors. In: Steinhoff, G. (eds) Regenerative Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9075-1_16

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