Skip to main content
SpringerLink
Log in

Mesenchymal Stem Cells – An Oversimplified Nomenclature for Extremely Heterogeneous Progenitors

  • Chapter
  • First Online:
Regenerative Medicine

  • 2215 Accesses

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. In the last 15 years, a huge number of different preparative protocols have been developed to yield MSC-like cell lines from starting materials as diverse as bone marrow, fat tissue, umbilical cord blood and peripheral blood. However, these protocols as well as the resulting cell populations are heterogeneous. Furthermore, the composition of the cell products and their 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 huge 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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

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):348–358

    PubMed  CAS  Google Scholar 

  • Anderson DG, Levenberg S, Langer R (2004) Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotechnol 22:863–866

    PubMed  CAS  Google Scholar 

  • Baptista LS, do Amaral RJ, Carias RB, Aniceto M, Claudio-da-Silva C, Borojevic R (2009) An alternative method for the isolation of mesenchymal stromal cells derived from lipoaspirate samples. Cytotherapy 11(6):706–715

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 22:625–634

    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):2331–2341

    PubMed  CAS  Google Scholar 

  • Bieback K, Wuchter P, Besser D, Franke W, Becker M, Ott M, Pacher M, Ma N, Stamm C, Klüter H, Müller A, Ho AD; START-MSC Consortium (2012) Mesenchymal stromal cells (MSCs): science and f(r)iction. J Mol Med 90(7):773–782

    Google Scholar 

  • Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, 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 (2010) DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells. Aging Cell 9(1):54–63

    Google Scholar 

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

    PubMed  Google Scholar 

  • Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650

    PubMed  CAS  Google Scholar 

  • Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084

    PubMed  CAS  Google Scholar 

  • Chambers SM, Shaw CA, Gatza C, Fisk CJ, Donehower LA, 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

    PubMed  CAS  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 98:7841–7845

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 119:2204–2213

    Google Scholar 

  • de Girolamo L, Sartori MF, Albisetti W, Brini AT (2007) Osteogenic differentiation of human adipose-derived stem cells: comparison of two different inductive media. J Tissue Eng Regen Med 1(2):154–157

    PubMed  Google Scholar 

  • Di Donna S, Mamchaoui K, Cooper RN, Seigneurin-Venin S, Tremblay J, Butler-Browne GS, 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 107:275–281

    PubMed  CAS  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 8:315–317

    PubMed  CAS  Google Scholar 

  • Engler AJ, Sen S, Sweeney HL et al (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689

    PubMed  CAS  Google Scholar 

  • Erices A, Conget P, Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109:235–242

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Fehrer C, Laschober G, Lepperdinger G (2006) Aging of murine mesenchymal stem cells. Ann N Y Acad Sci 1067:235–242

    PubMed  CAS  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 25:121–141

    PubMed  CAS  Google Scholar 

  • Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16:381–390

    PubMed  CAS  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 6:230–247

    PubMed  CAS  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 17:331–340

    PubMed  CAS  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 38:144–153

    PubMed  CAS  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):239–243

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Heid HW, Moll R, Schwetlick I, Rackwitz HR, Keenan TW (1998) Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res 294(2):309–321

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 10(7):676–685

    PubMed  CAS  Google Scholar 

  • Horwitz EM, Keating A (2000) Nonhematopoietic mesenchymal stem cells: what are they? Cytotherapy 2:387–388

    PubMed  CAS  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 7:393–395

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Javazon EH, Beggs KJ, Flake AW (2004) Mesenchymal stem cells: paradoxes of passaging. Exp Hematol 32:414–425

    PubMed  CAS  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 418:41–49. Corrigendum (2007) Nature 447:880–881

    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

    PubMed  CAS  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):11854–11860

    PubMed  CAS  Google Scholar 

  • Johnstone B, Hering TM, Caplan AI et al (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238:265–272

    PubMed  CAS  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 449(7162):557–563

    PubMed  CAS  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 24:1294–1301

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  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 25:1270–1278

    PubMed  CAS  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 200:123–135

    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 11:663–673

    PubMed  CAS  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):857–869

    PubMed  CAS  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):125–134

    PubMed  CAS  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):2083–2092

    PubMed  CAS  Google Scholar 

  • Kuznetsov SA, Mankani MH, Gronthos S et al (2001) Circulating skeletal stem cells. J Cell Biol 153:1133–1140

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Le Blanc K (2006) Mesenchymal stromal cells: tissue repair and immune modulation. Cytotherapy 8(6):559–561

    PubMed  Google Scholar 

  • Le Blanc K, Ringdén O (2007) Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med 262(5):509–525

    PubMed  Google Scholar 

  • Le Blanc K, Samuelsson H, Gustafsson B, Remberger M, Sundberg B, Arvidson J, Ljungman P, Lönnies H, Nava S, Ringdén O (2007) Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 21(8):1733–1738

    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 371(9624):1579–1586

    PubMed  Google Scholar 

  • Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675

    PubMed  CAS  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 (2010) Transformation potential of bone marrow stromal cells into undifferentiated high-grade pleomorphic sarcoma. J Cancer Res Clin Oncol 136(6):829–838

    Google Scholar 

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

    PubMed  CAS  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, Hahn WC (2003) Telomerase maintains telomere structure in normal human cells. Cell 114:241–253

    PubMed  CAS  Google Scholar 

  • Mazhari R, 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–S26

    PubMed  Google Scholar 

  • Meza-Zepeda LA, Noer A, Dahl JA, Micci F, Myklebost O, 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

    PubMed  CAS  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 8:268–273

    PubMed  CAS  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 8:437–444

    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):2054–2061

    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 11:181–188

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    PubMed  CAS  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 30:783–791

    PubMed  CAS  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 203:542–554

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Sabatini F, Petecchia L, Tavian M, Jodon de Villeroché V, Rossi GA, Brouty-Boyé D (2005) Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab Invest 85:962–971

    PubMed  CAS  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):1436–1446

    PubMed  CAS  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 95(6):867–874

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Secco M, Zucconi E, Vieira NM, Fogaça LL, Cerqueira A, Carvalho MD, Jazedje T, Okamoto OK, Muotri AR, Zatz M (2008a) Mesenchymal stem cells from umbilical cord: do not discard the cord! Neuromuscul Disord 18(1):17–18

    PubMed  Google Scholar 

  • Secco M, Zucconi E, Vieira NM, Fogaça LL, Cerqueira A, Carvalho MD, Jazedje T, Okamoto OK, Muotri AR, Zatz M (2008b) Multipotent stem cells from umbilical cord: cord is richer than blood! Stem Cells 26(1):146–150

    PubMed  CAS  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, 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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Sotiropoulou PA, Perez SA, Salagianni M et al (2006) Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 24:462

    PubMed  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–S56

    PubMed  Google Scholar 

  • Stenderup K, Justesen J, Clausen C, 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, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129:163–173

    PubMed  CAS  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 32:1212–1225

    PubMed  CAS  Google Scholar 

  • Suzuki T, Farrar JE, Yegnasubramanian S, Zahed M, Suzuki N, 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 416:542–545

    PubMed  CAS  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

    PubMed  CAS  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):371–379

    PubMed  CAS  Google Scholar 

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

    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 33:1402–1416

    PubMed  CAS  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 23:1180–1191

    PubMed  CAS  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 34:536–548

    PubMed  CAS  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 35:314–325

    PubMed  CAS  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):160–169

    PubMed  Google Scholar 

  • Wagner W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V, 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, Ho AD (2009) Aging and replicative senescence have related effects on human stem and progenitor cells. PLoS One 4:e5846

    PubMed  Google Scholar 

  • Wagner W, Bork S, Lepperdinger G, Joussen S, Ma N, Strunk D, Koch C (2010a) How to track cellular aging of mesenchymal stromal cells. Aging 2:224–230

    PubMed  CAS  Google Scholar 

  • Wagner W, Ho AD, Zenke M (2010b) Different facets of aging in human mesenchymal stem cells. Tissue Eng Part B Rev 16:445–453

    PubMed  Google Scholar 

  • Walenda T, Bork S, Horn P, Wein F, Saffrich R, Diehlmann A, Eckstein V, Ho AD, Wagner W (2010) Co-culture with mesenchymal stromal cells increases proliferation and maintenance of hematopoietic progenitor cells. J Cell Mol Med 14(1–2):337–350

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Wuchter P, Boda-Heggemann J, Straub BK, Grund C, Kuhn C, Krause U, Seckinger A, Peitsch WK, Spring H, Ho AD, 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, Ho AD (2008) Human hematopoietic stem cells and leukemic cells form cadherin-catenin based junctional complexes with mesenchymal stromal cells. Blood (ASH Annu Meet Abstr) 112:1367

    Google Scholar 

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

    Google Scholar 

  • Ying QL, Nichols J, Evans EP et al (2002) Changing potency by spontaneous fusion. Nature 416:545–548

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Zeddou M, Briquet A, Relic B, Josse C, Malaise MG, Gothot A, Lechanteur C, Beguin Y (2010) The umbilical cord matrix is a better source of mesenchymal stem cells (MSC) than the umbilical cord blood. Cell Biol Int 34(7):693–701

    PubMed  Google Scholar 

  • Zeng L, Rahrmann E, Hu Q et al (2006) Multipotent adult progenitor cells from swine bone marrow. Stem Cells 24:2355–2366

    PubMed  CAS  Google Scholar 

  • Zhou S, Greenberger JS, Epperly MW, Goff JP, Adler C, Leboff MS, 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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228

    PubMed  CAS  Google Scholar 

  • Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, Maini RN (2000) Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2(6):477–488

    PubMed  CAS  Google Scholar 

Download references

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 (SFB 873), 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.

Author information

Authors and Affiliations

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

    Patrick Wuchter M.D. & Anthony D. Ho M.D., FRCPC

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

    Wolfgang Wagner M.D., Ph.D.

Authors
  1. Patrick Wuchter M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Wagner M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anthony D. Ho M.D., FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anthony D. Ho M.D., FRCPC .

Editor information

Editors and Affiliations

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

    Gustav Steinhoff

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Wuchter, P., Wagner, W., Ho, A.D. (2013). Mesenchymal Stem Cells – An Oversimplified Nomenclature for Extremely Heterogeneous Progenitors. In: Steinhoff, G. (eds) Regenerative Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5690-8_16

Download citation

Publish with us

Policies and ethics

Search

Navigation