Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications

  • Danielle Minteer
  • Kacey G. Marra
  • J. Peter RubinEmail author
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 129)


Adipose tissue is derived from the mesoderm during embryonic development and is present in every mammalian species, located throughout the body. Adipose tissue serves as an endocrine organ, functioning to maintain energy metabolism through the storage of lipids. While two types of adipose tissue exist (brown and white), white adipose yields the commonly studied adipose-derived stem cells (ASCs). Adipose-derived stem cells provide a promising future in the field of tissue engineering and regenerative medicine. Due to their wide availability and ability to differentiate into other tissue types of the mesoderm—including bone, cartilage, muscle, and adipose—ASCs may serve a wide variety of applications. Adipose stem cells have been utilized in studies addressing osteoarthritis, diabetes mellitus, heart disease, and soft tissue regeneration and reconstruction after mastectomy and facial repair. Various delivery systems and scaffolds to incorporate adipose stem cells have also been established. Adipose stem cells have been studied in vitro and in vivo. Much information in vitro has been obtained on adipose stem cell potency and biology as a function of donor gender, body mass index, and anatomical location. Further in vitro studies have examined the various cell populations within the heterogeneous population within the stromal vascular fraction (SVF) from which ASCs are obtained. While many animal models are used to investigate adipose tissue, preclinical in vivo experiments are most widely conducted in the mouse model. Common analyses of animal studies utilizing ASCs include pre-labeling cells and immunostaining cells.

Graphical Abstract


Adipose tissue biology Mesenchymal stem cells Adipose stem cells 


  1. 1.
    Cinti S (1999) The adipose organ. Editrice Kurtis, MilanGoogle Scholar
  2. 2.
    Nedergaard J, Bengtsson T, Cannon B (2007) Unexpected evidence for active brown adipose tissue in adult humans. Am J Phys Endocrinol Metab 293(2):E444–E452CrossRefGoogle Scholar
  3. 3.
    Celi FS (2009) Brown adipose tissue—when it pays to be inefficient. N Engl J Med 360:1553CrossRefGoogle Scholar
  4. 4.
    “Adipocyte Function” Laboratory of Translational Nutritional Biology, Swiss Federal Institute of Technology Zurich; 11 Aug 2011. Accessed 6 Feb 2012
  5. 5.
    Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89(6):2548–2566CrossRefGoogle Scholar
  6. 6.
    Greenberg AS, Obin MS (2006) Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 83(Suppl):461S–465SGoogle Scholar
  7. 7.
    Freedman MR, Horwitz BA, Stern JS (1986) Effect of adrenalectomy and glucocorticoid replacement on development of obesity. Am J Phys 250:R595–R607Google Scholar
  8. 8.
    Picon L, Levacher C (1979) Thyroid hormones and adipose tissue development. J Phys 75:539–543Google Scholar
  9. 9.
    Hausman GJ, Wright JT, Dean R, Richardson RL (1993) Cellular and molecular aspects of the regulation of adipogenesis. J Anim Sci 71:33–55Google Scholar
  10. 10.
    Hausman GJ, Hausman DB (1993) Endocrine regulation of porcine adipose tissue development: cellular and metabolic aspects. In: Hollis GR (ed) Growth of the pig. CAB International, London, pp 49–73Google Scholar
  11. 11.
    Hausman GJ, Wright JT, Jewell DJ, Ramsay TG (1990) Fetal adipose tissue development. Int J Obes 14:177–185Google Scholar
  12. 12.
    Anderson KM, Kannel WB (1992) Obesity and disease. In: Bjorntorp P, Brodoff BN (eds) Obesity. J.B Lippincott Co, Philadelphia, pp 465–473Google Scholar
  13. 13.
    Matsuzawa Y, Fujioka S, Tokunaga K, Seichiro T (1992) Classification of obesity with respect to morbidity. Proc Soc Exp Biol Med 200:197–201Google Scholar
  14. 14.
    Montague CT, O-Rahilly S (2000) The perils of portliness. Diabetes 49:883–888CrossRefGoogle Scholar
  15. 15.
    Pi-Sunyer FX (1993) Health hazards of obesity. Ann Intern Med 119:655–660CrossRefGoogle Scholar
  16. 16.
    Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS (2001) Prevalence of obesity, diabetes, and obesity-related health risk factors. J Am Med Assoc 289:76–79CrossRefGoogle Scholar
  17. 17.
    “U.S. Obesity Trends” Centers for Disease Control and Prevention; 21 July 2011. Accessed 12 Feb 2012
  18. 18.
    Horowitz JF, Klein S (2000) Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women. Am J Phys Endocrinol Metab 278:E1144–E1152Google Scholar
  19. 19.
    Horowitz JF, Coppack SW, Paramore D, Cryer PE, Zhao G, Klein S (1999) Effect of short-term fasting on lipid kinetics in lean and obese women. Am J Phys 276:E278–E284Google Scholar
  20. 20.
    Ouchi N, Parker JL, Lugus JL, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85–97CrossRefGoogle Scholar
  21. 21.
    “Metabolic Syndrome” Penn State University, Milton S. Hershey Medical Center; 13 May 2010. Accessed 12 Feb 2012
  22. 22.
    “Cytori | Restoring Lives” 6 February 2012. Accessed 12 Feb 2012
  23. 23.
    Hollenberg CH, Vost A (1968) Regulation of DNA synthesis in fat cells and stromal elements from rat adipose tissue. J Clin Invest 47:2485–2498CrossRefGoogle Scholar
  24. 24.
    Stiles JW, Francendese AA, Masoro EJ (1975) Influence of age on size and number of fat cells in the epididymal depot. Am J Phys 229(6):1561–1568Google Scholar
  25. 25.
    Dardick I, Poznanski WJ, Waheed I, Steerfield G (1976) Ultrastructural observations on differentiating human preadipocytes cultured in vitro. Tissue Cell 8(3):561–571CrossRefGoogle Scholar
  26. 26.
    Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human aipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228CrossRefGoogle Scholar
  27. 27.
    Mehlhorn AT, Niemeyer P, Kaiser S, Finkenzeller G, Stark GB, Sudkamp NP, Schmal H (2006) Differential expression pattern of extracellular matrix molecules during chrondrogenesis of mesenchymal stem cells from bone marrow and adipose tissue. Tissue Eng 12(10):2853–2862CrossRefGoogle Scholar
  28. 28.
    Zimmerlin L, Donnenberg VS, Pfeifer ME, Meyer EM, Peault B, Rubin JP, Donnenberg AD (2010) Stromal vascular progenitors in adult human adipose tissue. Cytometry A 77(1):22–30Google Scholar
  29. 29.
    Planat-Bénard V, Menard C, André C, Puceat P, Perez A, Garcia-Verdugo JM, Pénicaud L, Casteilla L (2004) Spontaneous cardiomyocyte differentiation from adipose tissue stroma cells. Circ Res 94:223–229CrossRefGoogle Scholar
  30. 30.
    Brayfield C, Marra K, Rubin JP (2010) Adipose stem cells for soft tissue regeneration. Plast Chir 42:124–128Google Scholar
  31. 31.
    Bunnell BA, Estes BT, Guilak F, Gimble JM (2008) Differentiation of adipose stem cells. Met Mol Biol 456:155–171CrossRefGoogle Scholar
  32. 32.
    Frye CA, Patrick CW (2006) Three-dimensional adipose tissue model using low shear bioreactor. In Vitro Cell Dev Biol 42(5):109–114CrossRefGoogle Scholar
  33. 33.
    Gerlach JC, Lin YC, Brayfield CA, Minteer DM, Li H, Rubin JP, Marra KG (2012) Adipogenesis of human adipose-derived stem cells within three-dimensional hollow fiber-based bioreactors. Tissue Eng C 18(1):54–61CrossRefGoogle Scholar
  34. 34.
    Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13(12):4279–4295CrossRefGoogle Scholar
  35. 35.
    Lee JH, Kemp DM (2006) Human adipose-derived stem cells display myogenic potential and perturbed function in hypoxic conditions. Biochem Biophys Res Commun 341(3):882–888CrossRefGoogle Scholar
  36. 36.
    Rodriguez LV, Alfonso ZC, Zhang R, Leung J, Wu B, Ignarro LJ (2006) Clonogenic multipotent stem cells in human adipose tissue differentiate in muscle cells. PNAS 103(32):12167–12172CrossRefGoogle Scholar
  37. 37.
    Gaustad KG, Boquest AC, Anderson BE, Gerdes AM, Collas P (2004) Differentiation of human adipose tissue stem cells using extracts of rat cardiomyocytes. Biochem Biophys Res Commun 314(2):420–427CrossRefGoogle Scholar
  38. 38.
    Miranville A, Heeschen C, Sengenés C, Curat CA, Busse R, Bouloumié A (2004) Development of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110:349–355CrossRefGoogle Scholar
  39. 39.
    Choi YS, Cha SM, Lee YY, Kwon SW, Park CJ, Kim M (2006) Adipogenic differentiation of adipose tissue derived adult stem cells in nude mouse. Biochem Biophys Res Commun 345(2):631–637CrossRefGoogle Scholar
  40. 40.
    Lin Y, Chen X, Yan Z, Liu L, Tang W, Zheng X, Zhiyong L, Qiao J, Li S, Tian W (2006) Multilineage differentiation of adipose-derived stromal cells from GFP transgenic mice. Mol Cell Biochem 285(1–2):69–78Google Scholar
  41. 41.
    Ning H, Lin G, Lue TF, Lin CS (2006) Neuron-like differentiation of adipose tissue-derived stromal cells and vascular smooth muscle cells. Differentiation 74(9–10):510–518CrossRefGoogle Scholar
  42. 42.
    Cowan CM, Aalami OO, Shi YY, Chou YF, Mari C, Thomas R, Quarto N, Nacamuli RP, Contag CH, Wu B, Longaker MT (2005) Bone morphogenetic protein 2 and retinoic acid accelerate in vivo bone formation, osteoclast recruitment, and bone turnover. Tissue Eng 11(3–4):645–658CrossRefGoogle Scholar
  43. 43.
    DiRocoo G, Iachininoto MG, Tritarelli A, Straino S, Zacheo A, Germani A, Crea F, Capogrossi MC (2006) Myogenic potential of adipose-tissue-derived cells. J Cell Sci 119(4):2945–2952CrossRefGoogle Scholar
  44. 44.
    Miyahara Y, Nagaya N, Kataoka K, Yanagawa B, Tanaka K, Hao H, Ishino K, Ishida H, Shimizu T, Kangawa K, Sano S, Okano T, Kitamura S, Mori H (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12(4):459–465CrossRefGoogle Scholar
  45. 45.
    Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso ZC, Schreiber RE, Fraser JK, Hedrick MH (2005) Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 54(3):132–141CrossRefGoogle Scholar
  46. 46.
    Ando H, Yanagihara H, Hayashi Y, Obi Y, Tsuruoka S, Takamura T, Kaneko S, Fujimura A (2005) Rhythmic messenger ribonucleic acid expression of clock genes and adipocytokines in mouse visceral adipose tissue. Endocrinology 146(12):5631–5636CrossRefGoogle Scholar
  47. 47.
    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):355–366CrossRefGoogle Scholar
  48. 48.
    Constantin G, Marcon S, Rossi B, Angiari S, Calderan L, Anghileri E, Gini B, Bach SD, Martinello M, Bifari F, Galie M, Turano E, Budui S, Sbarbati A, Krampera M, Bonetti B (2009) Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 27(10):2624–2635CrossRefGoogle Scholar
  49. 49.
    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):142–150CrossRefGoogle Scholar
  50. 50.
    Visconti RT, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gomez-Lechon MJ (2006) Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol 12(036):5834–5845Google Scholar
  51. 51.
    Seo MJ, Suh SY, Bae YC, Jung JS (2005) Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 328(1):258–264CrossRefGoogle Scholar
  52. 52.
    Chandra V, Swetha G, Phadnis S, Nair PD, Bhonde RR (2009) Generation of pancreatic hormone-expressing islet-like cell aggregates from murine adipose tissue-derived stem cells. Stem Cells 27(8):1941–1953CrossRefGoogle Scholar
  53. 53.
    Kajiyama H (2010) Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice. Int J Dev Biol 54(4):699–705CrossRefGoogle Scholar
  54. 54.
    Schipper BM, Marra KG, Zhang W, Donnenberg AD, Rubin JP (2008) Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plast Surg 60(5):538–544CrossRefGoogle Scholar
  55. 55.
    Emre Aksu A, Rubin JP, Dudas JR, Marra KG (2008) Role of gender and anatomical region on induction of osteogenic differentiation of human adipose-derived stem cells. Ann Plast Surg 60(3):306–320CrossRefGoogle Scholar
  56. 56.
    Green H, Kehinde O (1975) An established preadipose cell line and its differentiation in culture II. Factors affecting the adipose conversion. Cell 5(1):19–27CrossRefGoogle Scholar
  57. 57.
    Rubin JP, Marra KG (2011) Soft tissue reconstruction. Methods Mol Bio 702:395–400CrossRefGoogle Scholar
  58. 58.
    Brayfield CA, Marra KG, Rubin JP (2010) Adipose stem cells for soft tissue regeneration. Handchir Mikrochir Plast Chir 42:124–128CrossRefGoogle Scholar
  59. 59.
    Choi YS, Cha SM, Lee YY, Kwon SW, Park CJ, Kim M (2006) Adipogenic differentiation of adipose tissue derived adult stem cells in nude mouse. Biochem Biophys Res Commun 345:631–637CrossRefGoogle Scholar
  60. 60.
    Kimura Y, Ozeki M, Inamoto T, Tabata Y (2003) Adipose tissue engineering based on human preadipocytes combined with gelatin microspheres containing basic fibroblast growth factor. Biomat 24:2513–2521CrossRefGoogle Scholar
  61. 61.
    Cho SW, Kim I, Kim SH, Rhie JW, Choi CY, Kim BS (2006) Enhancement of adipose tissue formation by implantation of adipogenic-differentiated preadipocytes. Biochem Biophys Res Commun 345:588CrossRefGoogle Scholar
  62. 62.
    Mazo M, Planat-Benard V, Abizanda G, Pelacho B, Leobon B, Gavira JJ, Penuelas I, Cemborain A, Penicaud L, Laharrague P, Joffre C, Boisson M, Ecay M, Collantes M, Barba J, Casteilla L, Prosper F (2008) Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction. Eur J Heart Fail 10(5):454–462CrossRefGoogle Scholar
  63. 63.
    Bel A, Planat-Benard V, Ssaito A, Bonnevie L, Bellamy V, Sabbah L, Bellabas L, Brinon B, Vanneaux V, Pradeau P, Peyrard S, Larghero J, Pouly J, Binder P, Garcia S, Shimizu T, Sawa Y, Okano T, Bruneval P, Desnos M, Hagege AA, Casteilla L, Puceat M, Menasche P (2010) Composite cell sheets: a further step towards safe and effective myocardial regeneration by cardiac progenitors derived from embryonic stem cells. Circulation 122:S118–S123CrossRefGoogle Scholar
  64. 64.
    Clavijo-Alvarez JA, Rubin JP, Bennett J, Nguyen VT, Dudas J, Underwood C, Marra KG (2006) A novel perfluoroelastomer seeded with adipose-derived stem cells for soft-tissue repair. Plast Reconstr Surg 118:1132CrossRefGoogle Scholar
  65. 65.
    Patrick C, Uthamanthil R, Beahm E, Frye C (2008) Animal models for adipose tissue engineering. Tissue Eng Part B Rev 14:167–178CrossRefGoogle Scholar
  66. 66.
    Kelmendi-Doko A, Marra KG, Tan H, Rakers A, Rubin JP (2011) Adipogenic factors effect in adipose tissue retention. In: International Federation of Adipose Therapeutics and Science. Eden Roc Renaissance Hotel, Miami, Florida, 5 Nov 2011Google Scholar
  67. 67.
    Li H, Zimmerlin L, Marra KG, Donnenberg VS, Donnenberg AD, Rubin JP (2011) Adipogenic potential of adipose stem cell subpopulations. Plast Reconstr Surg 128(3):663–672CrossRefGoogle Scholar
  68. 68.
    Philips BJ, Marra KG, Rubin JP (2012) Adipose stem cell-based soft tissue regeneration. Expert Opin Biol Ther 12(2):155–163CrossRefGoogle Scholar
  69. 69.
    Smith DM, Cooper GM, Afifi AM, Mooney MP, Cray J, Rubin JP, Marra KG, Losee JE (2011) Regenerative surgery in cranioplasty revisited: the role of adipose-derived stem cells and BMP-2. Plast Reconstr Surg 128(5):1053–1060CrossRefGoogle Scholar
  70. 70.
    Cherubino M, Rubin JP, Miljkovic N, Kelmendi-Doko A, Marra KG (2011) Adipose-derived stem cells for wound healing applications. Ann Plast Surg 66(2):210–215 ReviewCrossRefGoogle Scholar
  71. 71.
    Tan H, Rubin JP, Marra KG (2010) Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels for adipose tissue regeneration. Organogenesis 6(3):173–180CrossRefGoogle Scholar
  72. 72.
    Rubin JP, Marra KG (2011) Soft tissue reconstruction. Methods Mol Biol 702:395–400CrossRefGoogle Scholar
  73. 73.
    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):93–106CrossRefGoogle Scholar
  74. 74.
    Wada T, Ihunnah CA, Gao J, Chai X, Zeng S, Philips BJ, Rubin JP, Marra KG, Xie W (2011) Estrogen sulfotransferase inhibits adipocyte differentiation. Mol Endocrinol 25(9):1612–1623CrossRefGoogle Scholar
  75. 75.
    Marra KG, Defail AJ, Clavijo-Alvarez JA, Badylak SF, Taieb A, Schipper B, Bennett J, Rubin JP (2008) FGF-2 enhances vascularization for adipose tissue engineering. Plast Reconstr Surg 121(4):1153–1164CrossRefGoogle Scholar
  76. 76.
    Clavijo-Alvarez JA, Rubin JP, Bennett J, Nguyen VT, Dudas J, Underwood C, Marra KG (2006) A novel perfluoroelastomer seeded with adipose-derived stem cells for soft-tissue repair. Plast Reconstr Surg 118(5):1132–1142 discussion 1143−4CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Danielle Minteer
    • 1
  • Kacey G. Marra
    • 1
    • 2
    • 3
  • J. Peter Rubin
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of BioengineeringUniversity of PittsburghPittsburghUSA
  2. 2.Department of Plastic SurgeryUniversity of PittsburghPittsburghUSA
  3. 3.McGowan Institute for Regenerative MedicineUniversity of PittsburghPittsburghUSA
  4. 4.Division of Plastic SurgeryPittsburghUSA

Personalised recommendations