Experimental Hematology
Volume 36, Issue 5 , Pages 642-654 , May 2008

Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts

  • Dimas T. Covas

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
    • Corresponding Author InformationOffprint requests to: Dimas T. Covas, M.D., Ph.D., Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Hemocentro, R. Tenente Catão Roxo, 2501, 14051-140 Ribeirão Preto, Brazil
  • ,
  • Rodrigo A. Panepucci

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Aparecida M. Fontes

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Wilson A. Silva Jr.

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
    • Department of Genetics of Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Maristela D. Orellana

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Marcela C.C. Freitas

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Luciano Neder

      Affiliations

    • Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Anemari R.D. Santos

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Luiz C. Peres

      Affiliations

    • Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Maria C. Jamur

      Affiliations

    • Department of Cell and Molecular Biology, University of São Paulo, Ribeirão Preto, Brazil
  • ,
  • Marco A. Zago

      Affiliations

    • Department of Clinical Medicine, Center for Cell Therapy and Regional Blood Center, University of São Paulo, Ribeirão Preto, Brazil

Received 17 December 2007 ,Revised 17 December 2007 ,Accepted 21 December 2007.

References 

  1. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 1997;276(5309):71–74
  2. Horwitz EM, Le BK, Dominici M, et al. Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy. 2005;7:393–395
  3. Parker GC, Nastassova-Kristeva M, Eisenberg LM, et al. Stem cells: shibboleths of development, part II: toward a functional definition. Stem Cells Dev. 2005;14:463–469
  4. Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000;109:235–242
  5. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000;97:13625–13630
  6. Gronthos S, Franklin DM, Leddy HA, Robey PG, Storms RW, Gimble JM. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol. 2001;189:54–63
  7. Toma JG, Akhavan M, Fernandes KJ, et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 2001;3:778–784
  8. Asakura A, Komaki M, Rudnicki M. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation. 2001;68(4–5):245–253
  9. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood. 2001;98:2396–2402
  10. De Bari C, Dell'Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44:1928–1942
  11. Hu Y, Liao L, Wang Q, et al. Isolation and identification of mesenchymal stem cells from human fetal pancreas. J Lab Clin Med. 2003;141:342–349
  12. in 't Anker PS, Noort WA, Kruisselbrink AB, et al. Nonexpanded primary lung and bone marrow-derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol. 2003;31:881–889
  13. in't Anker PS, Scherjon SA, Kleijburg-Van Der Keur C, et al. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation. Blood. 2003;102:1548–1549
  14. in't Anker PS, Scherjon SA, Kleijburg-van der KC, et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells. 2004;22:1338–1345
  15. Roufosse CA, Direkze NC, Otto WR, Wright NA. Circulating mesenchymal stem cells. Int J Biochem Cell Biol. 2004;36:585–597
  16. Abedin M, Tintut Y, Demer LL. Mesenchymal stem cells and the artery wall. Circ Res. 2004;95:671–676
  17. Tintut Y, Alfonso Z, Saini T, et al. Multilineage potential of cells from the artery wall. Circulation. 2003;108:2505–2510
  18. Wissler RW, Vesselinovitch D. Comparative pathogenetic patterns in atherosclerosis. Adv Lipid Res. 1968;6:181–206
  19. Diaz-Flores L, Gutierrez R, Varela H, Rancel N, Valladares F. Microvascular pericytes: a review of their morphological and functional characteristics. Histol Histopathol. 1991;6:269–286
  20. Doherty MJ, Canfield AE. Gene expression during vascular pericyte differentiation. Crit Rev Eukaryot Gene Expr. 1999;9:1–17
  21. Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97:512–523
  22. Galmiche MC, Koteliansky VE, Briere J, Herve P, Charbord P. Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway. Blood. 1993;82:66–76
  23. Adams RH, Alitalo K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol. 2007;8:464–478
  24. Andreeva ER, Pugach IM, Gordon D, Orekhov AN. Continuous subendothelial network formed by pericyte-like cells in human vascular bed. Tissue Cell. 1998;30:127–135
  25. Shi S, Gronthos S. Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. J Bone Miner Res. 2003;18:696–704
  26. Postlethwaite AE, Shigemitsu H, Kanangat S. Cellular origins of fibroblasts: possible implications for organ fibrosis in systemic sclerosis. Curr Opin Rheumatol. 2004;16:733–738
  27. Schurch W, Seemayer TA, Gabbiani G. The myofibroblast: a quarter century after its discovery. Am J Surg Pathol. 1998;22:141–147
  28. Mazzucchelli L. Protein S100A4: too long overlooked by pathologists?. Am J Pathol. 2002;160:7–13
  29. Barraclough R. Calcium-binding protein S100A4 in health and disease. Biochim Biophys Acta. 1998;1448:190–199
  30. Hinz B. Formation and function of the myofibroblast during tissue repair. J Invest Dermatol. 2007;127:526–537
  31. Phan SH. The myofibroblast in pulmonary fibrosis. Chest. 2002;122(Suppl):286S–289S
  32. Lan HY. Tubular epithelial-myofibroblast transdifferentiation mechanisms in proximal tubule cells. Curr Opin Nephrol Hypertens. 2003;12:25–29
  33. Lotersztajn S, Julien B, Teixeira-Clerc F, Grenard P, Mallat A. Hepatic fibrosis: molecular mechanisms and drug targets. Annu Rev Pharmacol Toxicol. 2005;45:605–628
  34. Boers W, Aarrass S, Linthorst C, Pinzani M, Elferink RO, Bosma P. Transcriptional profiling reveals novel markers of liver fibrogenesis: gremlin and insulin-like growth factor-binding proteins. J Biol Chem. 2006;281:16289–16295
  35. Russo FP, Alison MR, Bigger BW, et al. The bone marrow functionally contributes to liver fibrosis. Gastroenterology. 2006;130:1807–1821
  36. Covas DT, Siufi JLC, Silva ARL, Orellana MD. Isolation and culture of umbilical vein mesenchymal stem cells. Braz J Med Biol Res. 2003;36:1179–1183
  37. Panepucci RA, Siufi JL, Silva WA, et al. Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells. 2004;22:1263–1278
  38. Silva WA, Covas DT, Panepucci RA, et al. The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells. 2003;21:661–669
  39. Covas DT, Piccinato CE, Orellana MD, et al. Mesenchymal stem cells can be obtained from the human saphena vein. Exp Cell Res. 2005;309:340–344
  40. Rubinstein P, Stevens CE. Placental blood for bone marrow replacement: the New York Blood Centers program and clinical results. Baillieres Best Pract Res Clin Haematol. 2000;13:565–584
  41. Doherty MJ, Ashton BA, Walsh S, Beresford JN, Grant ME, Canfield AE. Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res. 1998;13:828–838
  42. Takashima A. Establishment of fibroblast cultures. In:  Bonifacino JS,  Dasso M,  Harford JB, et al. editor. Current Protocols in Cell Biology. New York: John Wiley & Sons, Inc.; 1998;p. 2.1.1–2.1.12
  43. Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973;52:2745–2756
  44. Reynolds ES. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963;17:s208–s212
  45. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45
  46. de Hoon MJ, Imoto S, Nolan J, Miyano S. Open source clustering software. Bioinformatics. 2004;20:1453–1454
  47. Eisen MB, Spellman PT, Brown PO, Botstein D. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998;95:14863–14868
  48. Sorisky A, Pardasani D, Gagnon A, Smith TJ. Evidence of adipocyte differentiation in human orbital fibroblasts in primary culture. J Clin Endocrinol Metab. 1996;81:3428–3431
  49. Gronthos S, Simmons PJ. The growth factor requirements of STRO-1-positive human bone marrow stromal precursors under serum-deprived conditions in vitro. Blood. 1995;85:929–940
  50. Ball SG, Shuttleworth AC, Kielty CM. Direct cell contact influences bone marrow mesenchymal stem cell fate. Int J Biochem Cell Biol. 2004;36:714–727
  51. Kinner B, Zaleskas JM, Spector M. Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells. Exp Cell Res. 2002;278:72–83
  52. Ozerdem U, Grako KA, Hlin-Huppe K, Monosov E, Stallcup WB. NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev Dyn. 2001;222:218–227
  53. Vogel W, Grunebach F, Messam CA, Kanz L, Brugger W, Buhring HJ. Heterogeneity among human bone marrow-derived mesenchymal stem cells and neural progenitor cells. Haematologica. 2003;88:126–133
  54. Brachvogel B, Moch H, Pausch F, et al. Perivascular cells expressing annexin A5 define a novel mesenchymal stem cell-like population with the capacity to differentiate into multiple mesenchymal lineages. Development. 2005;132:2657–2668
  55. Carmeliet P, Collen D. Vascular development and disorders: molecular analysis and pathogenic insights. Kidney Int. 1998;53:1519–1549
  56. Muguruma Y, Yahata T, Miyatake H, et al. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood. 2006;107:1878–1887
  57. Sun XT, Zhang MY, Shu C, et al. Differential gene expression during capillary morphogenesis in a microcarrier-based three-dimensional in vitro model of angiogenesis with focus on chemokines and chemokine receptors. World J Gastroenterol. 2005;11:2283–2290
  58. Spanakis E, Brouty-Boye D. Discrimination of fibroblast subtypes by multivariate analysis of gene expression. Int J Cancer. 1997;71:402–409
  59. Fries KM, Blieden T, Looney RJ, et al. Evidence of fibroblast heterogeneity and the role of fibroblast subpopulations in fibrosis. Clin Immunol Immunopathol. 1994;72:283–292
  60. Chang HY, Chi JT, Dudoit S, et al. Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci U S A. 2002;99:12877–12882
  61. Rios H, Koushik SV, Wang H, et al. Periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. Mol Cell Biol. 2005;25:11131–11144
  62. Xu T, Bianco P, Fisher LW, et al. Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet. 1998;20:78–82
  63. Strutz F, Okada H, Lo CW, et al. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol. 1995;130:393–405
  64. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest. 2003;112:1776–1784
  65. Bardin N, George F, Mutin M, et al. S-Endo 1, a pan-endothelial monoclonal antibody recognizing a novel human endothelial antigen. Tissue Antigens. 1996;48:531–539
  66. Wilkinson FL, Liu Y, Rucka AK, et al. Contribution of VCAF-positive cells to neovascularization and calcification in atherosclerotic plaque development. J Pathol. 2007;211:362–369
  67. Yoshimura K, Shigeura T, Matsumoto D, et al. Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates. J Cell Physiol. 2006;208:64–76
  68. Bardin N, Anfosso F, Masse JM, et al. Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion. Blood. 2001;98:3677–3684
  69. Anfosso F, Bardin N, Vivier E, Sabatier F, Sampol J, Gnat-George F. Outside-in signaling pathway linked to CD146 engagement in human endothelial cells. J Biol Chem. 2001;276:1564–1569
  70. Salasznyk RM, Klees RF, Williams WA, Boskey A, Plopper GE. Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells. Exp Cell Res. 2007;313:22–37
  71. Salasznyk RM, Klees RF, Boskey A, Plopper GE. Activation of FAK is necessary for the osteogenic differentiation of human mesenchymal stem cells on laminin-5. J Cell Biochem. 2007;100:499–514
  72. Kundu AK, Putnam AJ. Vitronectin and collagen I differentially regulate osteogenesis in mesenchymal stem cells. Biochem Biophys Res Commun. 2006;347:347–357
  73. Baksh D, Yao R, Tuan RS. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25:1384–1392
  74. Delorme B, Basire A, Gentile C, et al. Presence of endothelial progenitor cells, distinct from mature endothelial cells, within human CD146+ blood cells. Thromb Haemost. 2005;94:1270–1279
  75. Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells. 2003;21:105–110
  76. Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005;23:220–229
  77. Pinzani M, Failli P, Ruocco C, et al. Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest. 1992;90:642–646
  78. Passino MA, Adams RA, Sikorski SL, Akassoglou K. Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR. Science. 2007;315(5820):1853–1856
  79. Buhring HJ, Battula VL, Treml S, Schewe B, Kanz L, Vogel W. Novel markers for the prospective isolation of human MSC. Ann N Y Acad Sci. 2007;1106:262–271
  80. Sartore S, Chiavegato A, Faggin E, et al. Contribution of adventitial fibroblasts to neointima formation and vascular remodeling: from innocent bystander to active participant. Circ Res. 2001;89:1111–1121
  81. Serini G, Gabbiani G. Mechanisms of myofibroblast activity and phenotypic modulation. Exp Cell Res. 1999;250:273–283
  82. Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada JI, West AB. Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol. 1999;277(1 Pt 1):C1–C9
  83. Panepucci RA, Calado RT, Rocha V, Proto-Siqueira R, Silva WA, Zago MA. Higher expression of transcription targets and components of the NF-{kappa}B pathway is a distinctive features of umbilical cord blood CD34+ precursors. Stem Cells. 2007;25:189–196
  84. Zhou G, Chen J, Lee S, Clark T, Rowley JD, Wang SM. The pattern of gene expression in human CD34(+) stem/progenitor cells. Proc Natl Acad Sci U S A. 2001;98:13966–13971
  85. Menssen A, Hermeking H. Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Proc Natl Acad Sci U S A. 2002;99:6274–6279
  86. Baross A, Schertzer M, Zuyderduyn SD, Jones SJ, Marra MA, Lansdorp PM. Effect of TERT and ATM on gene expression profiles in human fibroblasts. Genes Chromosomes Cancer. 2004;39:298–310
  87. Beauchamp NJ, van Achterberg TA, Engelse MA, Pannekoek H, de Vries CJ. Gene expression profiling of resting and activated vascular smooth muscle cells by serial analysis of gene expression and clustering analysis. Genomics. 2003;82:288–299
  88. Welle S, Bhatt K, Thornton CA. High-abundance mRNAs in human muscle: comparison between young and old. J Appl Physiol. 2000;89:297–304

PII: S0301-472X(08)00005-2

doi: 10.1016/j.exphem.2007.12.015

Experimental Hematology
Volume 36, Issue 5 , Pages 642-654 , May 2008