Skip to main content

Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications

  • Chapter
  • First Online:
Mesenchymal Stem Cells - Basics and Clinical Application I

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 129))

Abstract

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

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  1. Cinti S (1999) The adipose organ. Editrice Kurtis, Milan

    Google Scholar 

  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–E452

    Article  CAS  Google Scholar 

  3. Celi FS (2009) Brown adipose tissue—when it pays to be inefficient. N Engl J Med 360:1553

    Article  CAS  Google Scholar 

  4. “Adipocyte Function” Laboratory of Translational Nutritional Biology, Swiss Federal Institute of Technology Zurich; 11 Aug 2011. http://www.ifnh.ethz.ch/ftn/research/AdipFunct. Accessed 6 Feb 2012

  5. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89(6):2548–2566

    Article  CAS  Google Scholar 

  6. Greenberg AS, Obin MS (2006) Obesity and the role of adipose tissue in inflammation and metabolism. Am J Clin Nutr 83(Suppl):461S–465S

    CAS  Google Scholar 

  7. Freedman MR, Horwitz BA, Stern JS (1986) Effect of adrenalectomy and glucocorticoid replacement on development of obesity. Am J Phys 250:R595–R607

    CAS  Google Scholar 

  8. Picon L, Levacher C (1979) Thyroid hormones and adipose tissue development. J Phys 75:539–543

    CAS  Google Scholar 

  9. Hausman GJ, Wright JT, Dean R, Richardson RL (1993) Cellular and molecular aspects of the regulation of adipogenesis. J Anim Sci 71:33–55

    CAS  Google Scholar 

  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 49–73

    Google Scholar 

  11. Hausman GJ, Wright JT, Jewell DJ, Ramsay TG (1990) Fetal adipose tissue development. Int J Obes 14:177–185

    Google Scholar 

  12. Anderson KM, Kannel WB (1992) Obesity and disease. In: Bjorntorp P, Brodoff BN (eds) Obesity. J.B Lippincott Co, Philadelphia, pp 465–473

    Google Scholar 

  13. Matsuzawa Y, Fujioka S, Tokunaga K, Seichiro T (1992) Classification of obesity with respect to morbidity. Proc Soc Exp Biol Med 200:197–201

    CAS  Google Scholar 

  14. Montague CT, O-Rahilly S (2000) The perils of portliness. Diabetes 49:883–888

    Article  CAS  Google Scholar 

  15. Pi-Sunyer FX (1993) Health hazards of obesity. Ann Intern Med 119:655–660

    Article  CAS  Google Scholar 

  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 289:76–79

    Article  Google Scholar 

  17. “U.S. Obesity Trends” Centers for Disease Control and Prevention; 21 July 2011. http://www.cdc.gov/obesity/data/trends.HTML. Accessed 12 Feb 2012

  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–E1152

    CAS  Google Scholar 

  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–E284

    CAS  Google Scholar 

  20. Ouchi N, Parker JL, Lugus JL, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85–97

    Article  CAS  Google Scholar 

  21. “Metabolic Syndrome” Penn State University, Milton S. Hershey Medical Center; 13 May 2010. http://pennstatehershey.adam.com/content.aspx?productId=28&pid=28&gid=000284. Accessed 12 Feb 2012

  22. “Cytori | Restoring Lives” 6 February 2012. http://www.cytori.com. Accessed 12 Feb 2012

  23. Hollenberg CH, Vost A (1968) Regulation of DNA synthesis in fat cells and stromal elements from rat adipose tissue. J Clin Invest 47:2485–2498

    Article  CAS  Google Scholar 

  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):1561–1568

    CAS  Google Scholar 

  25. Dardick I, Poznanski WJ, Waheed I, Steerfield G (1976) Ultrastructural observations on differentiating human preadipocytes cultured in vitro. Tissue Cell 8(3):561–571

    Article  CAS  Google Scholar 

  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):211–228

    Article  CAS  Google Scholar 

  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):2853–2862

    Article  CAS  Google Scholar 

  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):22–30

    Google Scholar 

  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 94:223–229

    Article  Google Scholar 

  30. Brayfield C, Marra K, Rubin JP (2010) Adipose stem cells for soft tissue regeneration. Plast Chir 42:124–128

    CAS  Google Scholar 

  31. Bunnell BA, Estes BT, Guilak F, Gimble JM (2008) Differentiation of adipose stem cells. Met Mol Biol 456:155–171

    Article  Google Scholar 

  32. Frye CA, Patrick CW (2006) Three-dimensional adipose tissue model using low shear bioreactor. In Vitro Cell Dev Biol 42(5):109–114

    Article  CAS  Google Scholar 

  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):54–61

    Article  CAS  Google Scholar 

  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):4279–4295

    Article  CAS  Google Scholar 

  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):882–888

    Article  CAS  Google Scholar 

  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):12167–12172

    Article  CAS  Google Scholar 

  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):420–427

    Article  CAS  Google Scholar 

  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 110:349–355

    Article  CAS  Google Scholar 

  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):631–637

    Article  CAS  Google Scholar 

  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):69–78

    CAS  Google Scholar 

  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):510–518

    Article  CAS  Google Scholar 

  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):645–658

    Article  CAS  Google Scholar 

  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):2945–2952

    Article  Google Scholar 

  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):459–465

    Article  CAS  Google Scholar 

  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):132–141

    Article  CAS  Google Scholar 

  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):5631–5636

    Article  CAS  Google Scholar 

  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):355–366

    Article  CAS  Google Scholar 

  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):2624–2635

    Article  CAS  Google Scholar 

  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):142–150

    Article  CAS  Google Scholar 

  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):5834–5845

    Google Scholar 

  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):258–264

    Article  CAS  Google Scholar 

  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):1941–1953

    Article  CAS  Google Scholar 

  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):699–705

    Article  CAS  Google Scholar 

  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):538–544

    Article  CAS  Google Scholar 

  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):306–320

    Article  Google Scholar 

  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):19–27

    Article  CAS  Google Scholar 

  57. Rubin JP, Marra KG (2011) Soft tissue reconstruction. Methods Mol Bio 702:395–400

    Article  CAS  Google Scholar 

  58. Brayfield CA, Marra KG, Rubin JP (2010) Adipose stem cells for soft tissue regeneration. Handchir Mikrochir Plast Chir 42:124–128

    Article  CAS  Google Scholar 

  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 345:631–637

    Article  CAS  Google Scholar 

  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 24:2513–2521

    Article  CAS  Google Scholar 

  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 345:588

    Article  CAS  Google Scholar 

  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):454–462

    Article  Google Scholar 

  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–S123

    Article  Google Scholar 

  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 118:1132

    Article  CAS  Google Scholar 

  65. Patrick C, Uthamanthil R, Beahm E, Frye C (2008) Animal models for adipose tissue engineering. Tissue Eng Part B Rev 14:167–178

    Article  CAS  Google Scholar 

  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 2011

    Google Scholar 

  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):663–672

    Article  CAS  Google Scholar 

  68. Philips BJ, Marra KG, Rubin JP (2012) Adipose stem cell-based soft tissue regeneration. Expert Opin Biol Ther 12(2):155–163

    Article  CAS  Google Scholar 

  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):1053–1060

    Article  CAS  Google Scholar 

  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 Review

    Article  CAS  Google Scholar 

  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):173–180

    Article  Google Scholar 

  72. Rubin JP, Marra KG (2011) Soft tissue reconstruction. Methods Mol Biol 702:395–400

    Article  CAS  Google Scholar 

  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):93–106

    Article  CAS  Google Scholar 

  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):1612–1623

    Article  CAS  Google Scholar 

  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):1153–1164

    Article  CAS  Google Scholar 

  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 1143−4

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Peter Rubin .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Minteer, D., Marra, K.G., Rubin, J.P. (2012). Adipose-Derived Mesenchymal Stem Cells: Biology and Potential Applications. In: Weyand, B., Dominici, M., Hass, R., Jacobs, R., Kasper, C. (eds) Mesenchymal Stem Cells - Basics and Clinical Application I. Advances in Biochemical Engineering/Biotechnology, vol 129. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2012_146

Download citation

Publish with us

Policies and ethics