Adipose Tissue-Derived MSCs: Moving to the Clinic

  • Pedro P. Carvalho
  • Manuela E. Gomes
  • Rui L. Reis
  • Jeffrey M. Gimble
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Adipose tissue-derived stromal/stem cells (ASCs) are an abundant source of adult tissue stem cells for tissue engineering and regenerative medicine therapeutic applications. Unlike other sources of mesenchymal stromal/stem cells (MSCs), ASCs can be retrieved from liposuction aspirates or subcutaneous adipose tissue fragments in high numbers with minimal ethical considerations and can be easily expanded in vitro. The ASC have the ability to differentiate in vitro along endodermal, ectodermal, and mesodermal lineage pathways. Similar to other MSCs, ASCs display immunomodulatory and immunosuppressive properties, making them suitable for both autologous and allogeneic approaches. Furthermore, ASCs are genetically stable in short-term, although possibly not long term, culture. Due to these characteristics, ASCs are poised for clinical trials treating a broad range of conditions. Despite their tremendous promise, adipose tissue stem cell-based regenerative strategies may require additional preclinical evidence to support advancement to clinical trials. This chapter summarizes current preclinical and clinical data on the use of ASCs and discusses the future regenerative medical applications.

References

  1. 1.
    Nnodim JO (1987) Development of adipose tissues. Anat Rec 219(4):331–337PubMedCrossRefGoogle Scholar
  2. 2.
    Pansky A, Roitzheim B, Tobiasch E (2007) Differentiation potential of adult human mesenchymal stem cells. Clin Lab 53(1–2):81–84PubMedGoogle Scholar
  3. 3.
    Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5(5):362–369PubMedCrossRefGoogle Scholar
  4. 4.
    Halberstadt C, Austin C, Rowley J, Culberson C, Loebsack A, Wyatt S et al (2002) A hydrogel material for plastic and reconstructive applications injected into the subcutaneous space of a sheep. Tissue Eng 8(2):309–319PubMedCrossRefGoogle Scholar
  5. 5.
    Kral JG, Crandall DL (1999) Development of a human adipocyte synthetic polymer scaffold. Plast Reconstr Surg 104(6):1732–1738PubMedCrossRefGoogle Scholar
  6. 6.
    Patrick CW Jr, Zheng B, Johnston C, Reece GP (2002) Long-term implantation of preadipocyte-seeded PLGA scaffolds. Tissue Eng 8(2):283–293PubMedCrossRefGoogle Scholar
  7. 7.
    Gronthos S, Franklin DM, Leddy HA, Robey PG, Storms RW, Gimble JM (2001) Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol 189(1):54–63PubMedCrossRefGoogle Scholar
  8. 8.
    Williams SK, Wang TF, Castrillo R, Jarrell BE (1994) Liposuction-derived human fat used for vascular graft sodding contains endothelial cells and not mesothelial cells as the major cell type. J Vasc Surg 19(5):916–923PubMedGoogle Scholar
  9. 9.
    Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228PubMedCrossRefGoogle Scholar
  10. 10.
    Erickson GR, Gimble JM, Franklin DM, Rice HE, Awad H, Guilak F (2002) Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem Biophys Res Commun 290(2):763–769PubMedCrossRefGoogle Scholar
  11. 11.
    Awad HA, Halvorsen YD, Gimble JM, Guilak F (2003) Effects of transforming growth factor beta1 and dexamethasone on the growth and chondrogenic differentiation of adipose-derived stromal cells. Tissue Eng 9(6):1301–1312PubMedCrossRefGoogle Scholar
  12. 12.
    Hicok KC, Du Laney TV, Zhou YS, Halvorsen YD, Hitt DC, Cooper LF et al (2004) Human adipose-derived adult stem cells produce osteoid in vivo. Tissue Eng 10(3–4):371–380PubMedCrossRefGoogle Scholar
  13. 13.
    Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G et al (2007) Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 46(1):219–228PubMedCrossRefGoogle Scholar
  14. 14.
    Ruiz JC, Ludlow JW, Sherwood S, Yu G, Wu X, Gimble JM (2010) Differentiated human adipose-derived stem cells exhibit hepatogenic capability in vitro and in vivo. J Cell Physiol 225(2):429–436 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  15. 15.
    Brzoska M, Geiger H, Gauer S, Baer P (2005) Epithelial differentiation of human adipose tissue-derived adult stem cells. Biochem Biophys Res Commun 330(1):142–150PubMedCrossRefGoogle Scholar
  16. 16.
    Baer PC, Brzoska M, Geiger H (2011) Epithelial differentiation of human adipose-derived stem cells. Methods Mol Biol 702:289–298PubMedCrossRefGoogle Scholar
  17. 17.
    Franco Lambert AP, Fraga Zandonai A, Bonatto D, Cantarelli Machado D, Pegas Henriques JA (2009) Differentiation of human adipose-derived adult stem cells into neuronal tissue: does it work? Differentiation 77(3):221–228 [Journal Article Research Support, Non-U.S. Gov’t Review]PubMedCrossRefGoogle Scholar
  18. 18.
    Kokai LE, Rubin JP, Marra KG (2005) The potential of adipose-derived adult stem cells as a source of neuronal progenitor cells. Plast Reconstr Surg 116(5):1453–1460PubMedCrossRefGoogle Scholar
  19. 19.
    Safford KM, Hicok KC, Safford SD, Halvorsen YD, Wilkison WO, Gimble JM et al (2002) Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun 294(2):371–379PubMedCrossRefGoogle Scholar
  20. 20.
    Ashjian PH, Elbarbary AS, Edmonds B, DeUgarte D, Zhu M, Zuk PA et al (2003) In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. Plast Reconstr Surg 111(6):1922–1931PubMedCrossRefGoogle Scholar
  21. 21.
    Yu G, Floyd ZE, Wu X, Halvorsen YD, Gimble JM (2011) Isolation of human adipose-derived stem cells from lipoaspirates. Methods Mol Biol 702:17–27PubMedCrossRefGoogle Scholar
  22. 22.
    Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100(9):1249–1260PubMedCrossRefGoogle Scholar
  23. 23.
    Yu G, Wu X, Dietrich MA, Polk P, Scott LK, Ptitsyn AA, Gimble JM (2010) Yield and characterization of subcutaneous human adipose-derived stem cells by flow cytometric and adipogenic mRNA analyze. Cytotherapy 12:538–546PubMedCrossRefGoogle Scholar
  24. 24.
    Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13(12):4279–4295 [Journal Article Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.]PubMedCrossRefGoogle Scholar
  25. 25.
    McIntosh K, Zvonic S, Garrett S, Mitchell JB, Floyd ZE, Hammill L et al (2006) The immunogenicity of human adipose derived cells: temporal changes in vitro. Stem Cells 24:1245–1253CrossRefGoogle Scholar
  26. 26.
    Mitchell JB, McIntosh k, Zvonic S, Garrett S, Floyd ZE, Kloster A, Halvorsen YD, Storms RW, Goh B, Kilroy GS, Wu X, Gimble JM (2006) The immunophenotype of human adipose derived cells: temporal changes in stromal- and stem cell-associated markers. Stem Cells 24:376–385PubMedCrossRefGoogle Scholar
  27. 27.
    Zimmerlin L, Donnenberg VS, Pfeifer ME, Meyer EM, Peault B, Rubin JP et al (2010) Stromal vascular progenitors in adult human adipose tissue. Cytometry A 77(1):22–30 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]PubMedGoogle Scholar
  28. 28.
    Pachon-Pena G, Yu G, Tucker A, Wu X, Vendrell J, Bunnell B (2011) Stromal stem cells from adipose tissue and bone marrow of age matched female donors display distinct immunophenotypic profiles. J Cell Physiol 226(3):843–851PubMedCrossRefGoogle Scholar
  29. 29.
    Rada T, Reis RL, Gomes ME (2011) Distinct stem cells subpopulations isolated from human adipose tissue exhibit different chondrogenic and osteogenic differentiation potential. Stem Cell Rev 7(1):64–76PubMedCrossRefGoogle Scholar
  30. 30.
    Lin CS, Xin ZC, Deng CH, Ning H, Lin G, Lue TF (2010) Defining adipose tissue-derived stem cells in tissue and in culture. Histol Histopathol 25(6):807–815 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]PubMedGoogle Scholar
  31. 31.
    Riekstina U, Cakstina I, Parfejevs V, Hoogduijn M, Jankovskis G, Muiznieks I et al (2009) Embryonic stem cell marker expression pattern in human mesenchymal stem cells derived from bone marrow, adipose tissue, heart and dermis. Stem Cell Rev 5(4):378–386 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  32. 32.
    Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3(3):301–313 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.]PubMedCrossRefGoogle Scholar
  33. 33.
    Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R et al (2008) A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res 102(1):77–85, Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, Non-P.H.SPubMedCrossRefGoogle Scholar
  34. 34.
    Zannettino ACW, Paton S, Khor F, Itescu S, Gimble JM, Gronthos S (2008) Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J Cell Physiol 214:413–421PubMedCrossRefGoogle Scholar
  35. 35.
    Amos PJ, Shang H, Bailey AM, Taylor A, Katz AJ, Peirce SM (2008) IFATS collection: the role of human adipose-derived stromal cells in inflammatory microvascular remodeling and evidence of a perivascular phenotype. Stem Cells 26(10):2682–2690PubMedCrossRefGoogle Scholar
  36. 36.
    Lin G, Garcia M, Ning H, Banie L, Guo YL, Lue TF et al (2008) Defining stem and progenitor cells within adipose tissue. Stem Cells Dev 17(6):1053–1063 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  37. 37.
    Schaffler A, Buchler C (2007) Concise review: adipose tissue-derived stromal cells–basic and clinical implications for novel cell-based therapies. Stem Cells 25(4):818–827PubMedCrossRefGoogle Scholar
  38. 38.
    Salgado AJ, Reis RL, Sousa NJ, Gimble JM (2010) Adipose tissue derived stem cells secretome: soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther 5(2):103–110PubMedCrossRefGoogle Scholar
  39. 39.
    Halvorsen YD, Bond A, Sen A, Franklin DM, Lea-Currie YR, Sujkowski D et al (2001) Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: biochemical, cellular, and molecular analysis. Metabolism 50(4):407–413PubMedCrossRefGoogle Scholar
  40. 40.
    Palpant NJ, Metzger JM (2010) Aesthetic cardiology: adipose-derived stem cells for myocardial repair. Curr Stem Cell Res Ther 5(2):145–152PubMedCrossRefGoogle Scholar
  41. 41.
    Planat-Benard V, Menard C, Andre M, Puceat M, Perez A, Garcia-Verdugo JM et al (2004) Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 94(2):223–229PubMedCrossRefGoogle Scholar
  42. 42.
    Rangappa S, Fen C, Lee EH, Bongso A, Sim EK (2003) Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg 75(3):775–779PubMedCrossRefGoogle Scholar
  43. 43.
    Gwak SJ, Bhang SH, Yang HS, Kim SS, Lee DH, Lee SH et al (2009) In vitro cardiomyogenic differentiation of adipose-derived stromal cells using transforming growth factor-beta1. Cell Biochem Funct 27(3):148–154 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  44. 44.
    van Dijk A, Niessen HW, Zandieh Doulabi B, Visser FC, van Milligen FJ (2008) Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin. Cell Tissue Res 334(3):457–467 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  45. 45.
    Song YH, Gehmert S, Sadat S, Pinkernell K, Bai X, Matthias N et al (2007) VEGF is critical for spontaneous differentiation of stem cells into cardiomyocytes. Biochem Biophys Res Commun 354(4):999–1003PubMedCrossRefGoogle Scholar
  46. 46.
    Palpant NJ, Yasuda S, MacDougald O, Metzger JM (2007) Non-canonical Wnt signaling enhances differentiation of Sca1+/c-kit+adipose-derived murine stromal vascular cells into spontaneously beating cardiac myocytes. J Mol Cell Cardiol 43(3):362–370 [Journal Article Research Support, N.I.H., Extramural]PubMedCrossRefGoogle Scholar
  47. 47.
    Estes BT, Diekman BO, Gimble JM, Guilak F (2010) Isolation of adipose derived stem cells and their induction to a chondrogenic phenotype. Nat Protoc 5 7:1294–1311CrossRefGoogle Scholar
  48. 48.
    Casteilla L, Planat-Benard V, Cousin B, Laharrague P, Bourin P (2010) Vascular and endothelial regeneration. Curr Stem Cell Res Ther 5(2):141–144PubMedCrossRefGoogle Scholar
  49. 49.
    Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE et al (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109(10):1292–1298PubMedCrossRefGoogle Scholar
  50. 50.
    Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A (2004) Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110(3):349–355PubMedCrossRefGoogle Scholar
  51. 51.
    Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, Tamarat R et al (2004) Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 109(5):656–663PubMedCrossRefGoogle Scholar
  52. 52.
    Kilroy GE, Foster S, Wu X, Ruiz J, Sherwood S, Heifetz A, Ludlow JW, Stricker DM, Potiny S, Green P, Halvorsen YDC, Cheatham B, Storms RW, Gimble JM (2007) Cytokine profile of human adipose-derived stem cells: expression of angiogenic, hematopoietic, and Pro-inflammatory factors. J Cell Physiol 212(3):702–709PubMedCrossRefGoogle Scholar
  53. 53.
    Kim SJ, Cho HH, Kim YJ, Seo SY, Kim HN, Lee JB et al (2005) Human adipose stromal cells expanded in human serum promote engraftment of human peripheral blood hematopoietic stem cells in NOD/SCID mice. Biochem Biophys Res Commun 329(1):25–31PubMedCrossRefGoogle Scholar
  54. 54.
    Cousin B, Andre M, Arnaud E, Penicaud L, Casteilla L (2003) Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochem Biophys Res Commun 301(4):1016–1022PubMedCrossRefGoogle Scholar
  55. 55.
    Corre J, Barreau C, Cousin B, Chavoin JP, Caton D, Fournial G et al (2006) Human subcutaneous adipose cells support complete differentiation but not self-renewal of hematopoietic progenitors. J Cell Physiol 208(2):282–288PubMedCrossRefGoogle Scholar
  56. 56.
    Nakao N, Nakayama T, Yahata T, Muguruma Y, Saito S, Miyata Y et al (2010) Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo: advantages over bone marrow-derived mesenchymal stem cells. Am J Pathol 177(2):547–554 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  57. 57.
    Han J, Koh YJ, Moon HR, Ryoo HG, Cho CH, Kim I et al (2010) Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood 115(5):957–964 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  58. 58.
    Ishikawa T, Banas A, Hagiwara K, Iwaguro H, Ochiya T (2010) Stem cells for hepatic regeneration: the role of adipose tissue derived mesenchymal stem cells. Curr Stem Cell Res Ther 5(2):182–189PubMedCrossRefGoogle Scholar
  59. 59.
    Talens-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV et al (2006) Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol 12(36):5834–5845PubMedGoogle Scholar
  60. 60.
    Sgodda M, Aurich H, Kleist S, Aurich I, Konig S, Dollinger MM et al (2007) Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo. Exp Cell Res 313(13):2875–2886PubMedCrossRefGoogle Scholar
  61. 61.
    Mizuno H (2010) The potential for treatment of skeletal muscle disorders with adipose-derived stem cells. Curr Stem Cell Res Ther 5(2):133–136 [Journal Article Review]PubMedCrossRefGoogle Scholar
  62. 62.
    Mizuno H, Zuk PA, Zhu M, Lorenz HP, Benhaim P, Hedrick MH (2002) Myogenic differentiation by human processed lipoaspirate cells. Plast Reconstr Surg 109(1):199–209; discussion 10–11PubMedCrossRefGoogle Scholar
  63. 63.
    Erba P, Terenghi G, Kingham PJ (2010) Neural differentiation and therapeutic potential of adipose tissue derived stem cells. Curr Stem Cell Res Ther 5(2):153–160PubMedCrossRefGoogle Scholar
  64. 64.
    Safford KM, Safford SD, Gimble JM, Shetty AK, Rice HE (2004) Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells. Exp Neurol 187(2):319–328PubMedCrossRefGoogle Scholar
  65. 65.
    Kang SK, Putnam LA, Ylostalo J, Popescu IR, Dufour J, Belousov A et al (2004) Neurogenesis of rhesus adipose stromal cells. J Cell Sci 117(Pt 18):4289–4299PubMedCrossRefGoogle Scholar
  66. 66.
    Halvorsen YD, Franklin D, Bond AL, Hitt DC, Auchter C, Boskey AL et al (2001) Extracellular matrix mineralization and osteoblast gene expression by human adipose tissue-derived stromal cells. Tissue Eng 7(6):729–741PubMedCrossRefGoogle Scholar
  67. 67.
    Halvorsen YC, Wilkison WO, Gimble JM (2000) Adipose-derived stromal cells – their utility and potential in bone formation. Int J Obes Relat Metab Disord 24(Suppl 4):S41–S44PubMedCrossRefGoogle Scholar
  68. 68.
    Kim SC, Han DJ, Lee JY (2010) Adipose tissue derived stem cells for regeneration and differentiation into insulin-producing cells. Curr Stem Cell Res Ther 5(2):190–194PubMedCrossRefGoogle Scholar
  69. 69.
    Lin G, Wang G, Liu G, Yang LJ, Chang LJ, Lue TF et al (2009) Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1. Stem Cells Dev 18(10):1399–1406 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  70. 70.
    Timper K, Seboek D, Eberhardt M, Linscheid P, Christ-Crain M, Keller U et al (2006) Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun 341(4):1135–1140PubMedCrossRefGoogle Scholar
  71. 71.
    Lee J, Han DJ, Kim SC (2008) In vitro differentiation of human adipose tissue-derived stem cells into cells with pancreatic phenotype by regenerating pancreas extract. Biochem Biophys Res Commun 375(4):547–551 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  72. 72.
    Brayfield C, Marra K, Rubin JP (2010) Adipose stem cells for soft tissue regeneration. Handchir Mikrochir Plast Chir 42(2):124–128PubMedCrossRefGoogle Scholar
  73. 73.
    Eilertsen KJ, Floyd Z, Gimble JM (2008) The epigenetics of adult (somatic) stem cells. Critical Reviews in Eukaryotic Gene Expression. 18(3):189–206PubMedCrossRefGoogle Scholar
  74. 74.
    Guilak F, Lott KE, Awad HA, Cao Q, Hicok KC, Fermor B et al (2006) Clonal analysis of the differentiation potential of human adipose-derived adult stem cells. J Cell Physiol 206(1): 229–237PubMedCrossRefGoogle Scholar
  75. 75.
    Tanzi MC, Fare S (2009) Adipose tissue engineering: state of the art, recent advances and innovative approaches. Expert Rev Med Devices 6(5):533–551 [Journal Article Review]PubMedCrossRefGoogle Scholar
  76. 76.
    Uysal AC, Mizuno H (2010) Tendon regeneration and repair with adipose derived stem cells. Curr Stem Cell Res Ther 5(2):161–167 [Journal Article Review]PubMedCrossRefGoogle Scholar
  77. 77.
    Ochiya T, Yamamoto Y, Banas A (2010) Commitment of stem cells into functional hepatocytes. Differentiation 79(2):65–73 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  78. 78.
    de Villiers JA, Houreld N, Abrahamse H (2009) Adipose derived stem cells and smooth muscle cells: implications for regenerative medicine. Stem Cell Rev 5(3):256–265 [Journal Article Review]PubMedCrossRefGoogle Scholar
  79. 79.
    De Miguel MP, Alio JL, Arnalich-Montiel F, Fuentes-Julian S, de Benito-Llopis L, Amparo F et al (2010) Cornea and ocular surface treatment. Curr Stem Cell Res Ther 5(2):195–204PubMedCrossRefGoogle Scholar
  80. 80.
    Graf T (2011) Historical origins of transdifferentiation and reprogramming. Cell Stem Cell 9(6):504–516 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  81. 81.
    Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89(6):2548–2556PubMedCrossRefGoogle Scholar
  82. 82.
    Trayhurn P (2005) Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 184(4):285–293PubMedCrossRefGoogle Scholar
  83. 83.
    Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95(5):2409–2415PubMedCrossRefGoogle Scholar
  84. 84.
    Laharrague P, Casteilla L (2010) The emergence of adipocytes. Endocr Dev 19:21–30 [Journal Article Review]PubMedCrossRefGoogle Scholar
  85. 85.
    Hoffmann J, Glassford AJ, Doyle TC, Robbins RC, Schrepfer S, Pelletier MP (2010) Angiogenic effects despite limited cell survival of bone marrow-derived mesenchymal stem cells under ischemia. Thorac Cardiovasc Surg 58(3):136–142 [Comparative Study Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  86. 86.
    Samudio I, Fiegl M, McQueen T, Clise-Dwyer K, Andreeff M (2008) The warburg effect in leukemia-stroma cocultures is mediated by mitochondrial uncoupling associated with uncoupling protein 2 activation. Cancer Res 68(13):5198–5205 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  87. 87.
    Koc ON, Lazarus HM (2001) Mesenchymal stem cells: heading into the clinic. Bone Marrow Transplant 27(3):235–239PubMedCrossRefGoogle Scholar
  88. 88.
    Yanez R, Lamana ML, Garcia-Castro J, Colmenero I, Ramirez M, Bueren JA (2006) Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells 24(11):2582–2591PubMedCrossRefGoogle Scholar
  89. 89.
    Lindroos B, Suuronen R, Miettinen S (2011) The potential of adipose stem cells in regenerative medicine. Stem Cell Rev 7(2):269–291PubMedCrossRefGoogle Scholar
  90. 90.
    Mosna F, Sensebe L, Krampera M (2010) Human bone marrow and adipose tissue mesenchymal stem cells: a user’s guide. Stem Cells Dev 19(10):1449–1470 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  91. 91.
    Mizuno H (2010) Adipose-derived stem and stromal cells for cell-based therapy: current status of preclinical studies and clinical trials. Curr Opin Mol Ther 12(4):442–449 [Journal Article Review]PubMedGoogle Scholar
  92. 92.
    Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S et al (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30(1):42–48PubMedCrossRefGoogle Scholar
  93. 93.
    Puissant B, Barreau C, Bourin P, Clavel C, Corre J, Bousquet C et al (2005) Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol 129(1):118–129PubMedCrossRefGoogle Scholar
  94. 94.
    Cui L, Yin S, Liu W, Li N, Zhang W, Cao Y (2007) Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2. Tissue Eng 13:1185–1195PubMedCrossRefGoogle Scholar
  95. 95.
    Crop MJ, Baan CC, Korevaar SS, Ijzermans JN, Weimar W, Hoogduijn MJ (2010) Human adipose tissue-derived mesenchymal stem cells induce explosive T-cell proliferation. Stem Cells Dev 19(12):1843–1853PubMedCrossRefGoogle Scholar
  96. 96.
    McIntosh KR, Lopez MJ, Borneman JN, Spencer ND, Anderson PA, Gimble JM (2009) Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model. Tissue Eng Part A 15(9):2677–2686 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  97. 97.
    Yoo KH, Jang IK, Lee MW, Kim HE, Yang MS, Eom Y et al (2009) Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues. Cell Immunol 259(2):150–156 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  98. 98.
    Crop MJ, Baan CC, Korevaar SS, Ijzermans JN, Pescatori M, Stubbs AP et al (2010) Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clin Exp Immunol 162(3):474–486PubMedCrossRefGoogle Scholar
  99. 99.
    Cho KS, Roh HJ (2010) Immunomodulatory effects of adipose-derived stem cells in airway allergic diseases. Curr Stem Cell Res Ther 5(2):111–115PubMedCrossRefGoogle Scholar
  100. 100.
    Wang M, Crisostomo P, Herring C, Meldrum KK, Meldrum DR (2006) Human progenitor cells from bone marrow or adipose tissue produce vegf, hgf and igf-1 in response to tnf by a p38 mitogen acivated protein kinase dependent mechanism. Am J Physiol Regul Integr Comp Physiol 291(4):R880–R884PubMedCrossRefGoogle Scholar
  101. 101.
    Prichard HL, Reichert W, Klitzman B (2008) IFATS collection: adipose-derived stromal cells improve the foreign body response. Stem Cells 26(10):2691–2695 [Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  102. 102.
    Sterodimas A, de Faria J, Nicaretta B, Pitanguy I (2010) Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. J Plast Reconstr Aesthet Surg 63(11):1886–1892 [Journal Article Review]PubMedCrossRefGoogle Scholar
  103. 103.
    Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K et al (2010) Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J 16: 169–175PubMedCrossRefGoogle Scholar
  104. 104.
    Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K (2008) Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adipose-derived stem/stromal cells. Aesthetic Plast Surg 32(1):48–55; discussion 6–7PubMedCrossRefGoogle Scholar
  105. 105.
    Billings E Jr, May JW Jr (1989) Historical review and present status of free fat graft autotransplantation in plastic and reconstructive surgery. Plast Reconstr Surg 83(2):368–381PubMedCrossRefGoogle Scholar
  106. 106.
    Yoshimura K, Sato K, Aoi N, Kurita M, Inoue K, Suga H, Eto H, Kato H, Hirohi T, Harii K (2008) Cell-assisted lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived stem cells. Dermatol Surg 34:1178–1185PubMedCrossRefGoogle Scholar
  107. 107.
    Rigotti G, Marchi A, Galie M, Baroni G, Benati D, Krampera M et al (2007) Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg 119(5):1409–1422; discussion 23–24PubMedCrossRefGoogle Scholar
  108. 108.
    Jeong JH (2010) Adipose stem cells and skin repair. Curr Stem Cell Res Ther 5(2):137–140PubMedCrossRefGoogle Scholar
  109. 109.
    Brayfield CA, Marra KG, Rubin JP (2010) Adipose tissue regeneration. Curr Stem Cell Res Ther 5(2):116–121 [Journal Article Research Support, N.I.H., Extramural Review]PubMedCrossRefGoogle Scholar
  110. 110.
    Hyakusoku H, Ogawa R, Ono S, Ishii N, Hirakawa K (2009) Complications after autologous fat injection to the breast. Plast Reconstr Surg 123(1):360–370; discussion 71–72PubMedCrossRefGoogle Scholar
  111. 111.
    Zimmerlin L, Donnenberg AD, Rubin JP, Basse P, Landreneau RJ, Donnenberg VS (2011) Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates. Tissue Eng Part A 17(1–2):93–106PubMedCrossRefGoogle Scholar
  112. 112.
    Donnenberg VS, Zimmerlin L, Rubin JP, Donnenberg AD (2010) Regenerative therapy after cancer: what are the risks? Tissue Eng Part B Rev 16(6):567–575 [ournal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.]PubMedCrossRefGoogle Scholar
  113. 113.
    Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME (2006) Playing with bone and fat. J Cell Biochem 98(2):251–266PubMedCrossRefGoogle Scholar
  114. 114.
    Panetta NJ, Gupta DM, Longaker MT (2010) Bone regeneration and repair. Curr Stem Cell Res Ther 5(2):122–128PubMedCrossRefGoogle Scholar
  115. 115.
    Mesimaki K, Lindroos B, Tornwall J, Mauno J, Lindqvist C, Kontio R et al (2009) Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg 38(3):201–209 [Case Reports Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  116. 116.
    Thesleff T, Lehtimaki K, Niskakangas T, Mannerstrom B, Miettinen S, Suuronen R et al (2011) Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction. Neurosurgery 68(6):1535–1540PubMedCrossRefGoogle Scholar
  117. 117.
    Garcia-Olmo D, Garcia-Arranz M, Garcia LG, Cuellar ES, Blanco IF, Prianes LA et al (2003) Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn’s disease: a new cell-based therapy. Int J Colorectal Dis 18(5):451–454PubMedCrossRefGoogle Scholar
  118. 118.
    Garcia-Olmo D, Garcia-Arranz M, Herreros D (2008) Expanded adipose-derived stem cells for the treatment of complex perianal fistula including Crohn’s disease. Expert Opin Biol Ther 8(9):1417–1423PubMedCrossRefGoogle Scholar
  119. 119.
    Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA (2005) A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 48(7):1416–1423PubMedCrossRefGoogle Scholar
  120. 120.
    Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J et al (2009) Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum 52(1):79–86PubMedCrossRefGoogle Scholar
  121. 121.
    Garcia-Olmo D, Herreros D, Pascual M, Pascual I, De-La-Quintana P, Trebol J et al (2009) Treatment of enterocutaneous fistula in Crohn’s disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion. Int J Colorectal Dis 24(1):27–30PubMedCrossRefGoogle Scholar
  122. 122.
    Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M (2009) Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology 136(3):978–989 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  123. 123.
    Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E et al (2009) Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 27(10):2624–2635 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  124. 124.
    Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F et al (2009) Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med 7:29PubMedCrossRefGoogle Scholar
  125. 125.
    Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M (2009) Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 60(4):1006–1019 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  126. 126.
    Gonzalez-Rey E, Gonzalez MA, Varela N, O’Valle F, Hernandez-Cortes P, Rico L et al (2010) Human adipose-derived mesenchymal stem cells reduce inflammatory and T-cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann Rheum Dis 69(1):241–248PubMedCrossRefGoogle Scholar
  127. 127.
    Nakagami H, Morishita R, Maeda K, Kikuchi Y, Ogihara T, Kaneda Y (2006) Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J Atheroscler Thromb 13(2):77–81PubMedCrossRefGoogle Scholar
  128. 128.
    Bhang SH, Cho SW, Lim JM, Kang JM, Lee TJ, Yang HS et al (2009) Locally delivered growth factor enhances the angiogenic efficacy of adipose-derived stromal cells transplanted to ischemic limbs. Stem Cells 27(8):1976–1986PubMedCrossRefGoogle Scholar
  129. 129.
    Moon MH, Kim SY, Kim YJ, Kim SJ, Lee JB, Bae YC et al (2006) Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia. Cell Physiol Biochem 17(5–6):279–290PubMedCrossRefGoogle Scholar
  130. 130.
    Ii M, Horii M, Yokoyama A, Shoji T, Mifune Y, Kawamoto A et al (2011) Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart. Lab Invest 91(4):539–552PubMedCrossRefGoogle Scholar
  131. 131.
    Cai L, Johnstone BH, Cook TG, Tan J, Fishbein MC, Chen PS et al (2009) IFATS collection: human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells 27(1):230–237 [Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, Non-P.H.S.]PubMedCrossRefGoogle Scholar
  132. 132.
    Bai X, Yan Y, Song YH, Seidensticker M, Rabinovich B, Metzele R et al (2010) Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial infarction. Eur Heart J 31(4):489–501 [Journal Article Research Support, Non-U.S. Gov’t]PubMedCrossRefGoogle Scholar
  133. 133.
    Kim JM, Lee ST, Chu K, Jung KH, Song EC, Kim SJ et al (2007) Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model. Brain Res 1183:43–50PubMedCrossRefGoogle Scholar
  134. 134.
    Kim Y, Kim H, Cho H, Bae Y, Suh K, Jung J (2007) Direct comparison of human mesenchymal stem cells derived from adipose tissues and bone marrow in mediating neovascularization in response to vascular ischemia. Cell Physiol Biochem 20(6):867–876PubMedCrossRefGoogle Scholar
  135. 135.
    Kang SK, Lee DH, Bae YC, Kim HK, Baik SY, Jung JS (2003) Improvement of neurological deficits by intracerebral transplantation of human adipose tissue-derived stromal cells after cerebral ischemia in rats. Exp Neurol 183(2):355–366PubMedCrossRefGoogle Scholar
  136. 136.
    Kang SK, Shin MJ, Jung JS, Kim YG, Kim CH (2006) Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury. Stem Cells Dev 15(4):583–594PubMedCrossRefGoogle Scholar
  137. 137.
    Mosna F, Annunziato F, Pizzolo G, Krampera M (2010) Cell therapy for cardiac regeneration after myocardial infarct: which cell is the best? Cardiovasc Hematol Agents Med Chem 8(4):227–243PubMedCrossRefGoogle Scholar
  138. 138.
    Madonna R, De Caterina R (2010) Adipose tissue: a new source for cardiovascular repair. J Cardiovasc Med (Hagerstown) 11(2):71–80 [Journal Article Research Support, Non-U.S. Gov’t Review]CrossRefGoogle Scholar
  139. 139.
    Rubio D, Garcia-Castro J, Martin MC, de la Fuente R, Cigudosa JC, Lloyd AC et al (2005) Spontaneous human adult stem cell transformation. Cancer Res 65(8):3035–3039PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Pedro P. Carvalho
    • 1
  • Manuela E. Gomes
    • 1
  • Rui L. Reis
    • 1
  • Jeffrey M. Gimble
    • 2
  1. 1.3B’s Research Group, Biomaterials, Biodegradables and Biomimetics, Department of Polymer EngineeringUniversity of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineGuimarãesPortugal
  2. 2.Stem Cell Biology Laboratory, Pennington Biomedical Research CenterLouisiana State University SystemBaton RougeUSA

Personalised recommendations