Skip to main content

Challenges and Status of Adipose Cell Therapies: Translation and Commercialization

  • Living reference work entry
  • First Online:
Cell Engineering and Regeneration

Part of the book series: Reference Series in Biomedical Engineering ((TIENRE))

  • 368 Accesses

1 Introduction

Adipose tissue as a bio-resource. Previously perceived as dormant, adipose tissue has emerged over the last 16 years as a premier source of cells for evolving tissue engineering and regenerative therapies (Kapur et al. 2015). Because of their origin, adipose-derived cells (ADCs) do not carry the ethical overhead often present in the heated debates involving embryonic stem cells. They are one of several cell types garnered from several differing sources collectively known as adult stem cells. Recently, the idea that these cells are indeed true stem cells has come into question. Although they may not have the developmental flexibility and extended differentiation capacity seen in embryonic stem cells, their human application in the clinic is more likely in the near future. Indeed adipose tissue is now a widely studied tissue in the context of regenerative medicine and has been the subject of preclinical studies and clinical studies directed toward numerous applications...

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

Access this chapter

Institutional subscriptions

References

  • Akita S, Akino K, Hirano A, Ohtsuru A, Yamashita S (2010a) Mesenchymal stem cell therapy for cutaneous radiation syndrome. Health Phys 98(6):858–862

    Article  Google Scholar 

  • Akita S, Akino K, Hirano A, Ohtsuru A, Yamashita S (2010b) Noncultured autologous adipose-derived stem cells therapy for chronic radiation injury. Stem Cells Int 2010:532704

    Article  Google Scholar 

  • Alvarez PD, Garcia-Arranz M, Georgiev-Hristov T, Garcia-Olmo D (2008) A new bronchoscopic treatment of tracheomediastinal fistula using autologous adipose-derived stem cells. Thorax 63(4):374–376

    Article  Google Scholar 

  • Arnold F, West D, Kumar S (1987) Wound healing: the effect of macrophage and tumour derived angiogenesis factors on skin graft vascularization. Br J Exp Pathol 68(4):569–574

    Google Scholar 

  • Aronowitz JA, Lockhart RA, Hakakian CS (2015) Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue. Springerplus 4:713

    Article  Google Scholar 

  • Badylak SF, Valentin JE, Ravindra AK, McCabe GP, Stewart-Akers AM (2008) Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng A 14(11):1835–1842

    Article  Google Scholar 

  • Bajek A, Gurtowska N, Olkowska J, Kazmierski L, Maj M, Drewa T (2016) Adipose-derived stem cells as a tool in cell-based therapies. Arch Immunol Ther Exp 64:443

    Article  Google Scholar 

  • Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM (2013) Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy 15(6):641–648

    Article  Google Scholar 

  • Corliss BA, Azimi MS, Munson JM, Peirce SM, Murfee WL (2016) Macrophages: an inflammatory link between angiogenesis and lymphangiogenesis. Microcirculation 23(2):95–121

    Article  Google Scholar 

  • Dromard C, Bourin P, Andre M, De Barros S, Casteilla L, Planat-Benard V (2011) Human adipose derived stroma/stem cells grow in serum-free medium as floating spheres. Exp Cell Res 317(6):770–780

    Article  Google Scholar 

  • Fang B, Song Y, Liao L, Zhang Y, Zhao RC (2007a) Favorable response to human adipose tissue-derived mesenchymal stem cells in steroid-refractory acute graft-versus-host disease. Transplant Proc 39(10):3358–3362

    Article  Google Scholar 

  • Fang B, Song Y, Zhao RC, Han Q, Lin Q (2007b) Using human adipose tissue-derived mesenchymal stem cells as salvage therapy for hepatic graft-versus-host disease resembling acute hepatitis. Transplant Proc 39(5):1710–1713

    Article  Google Scholar 

  • Fang B, Song Y, Li N, Li J, Han Q, Zhao RC (2009a) Mesenchymal stem cells for the treatment of refractory pure red cell aplasia after major ABO-incompatible hematopoietic stem cell transplantation. Ann Hematol 88(3):261–266

    Article  Google Scholar 

  • Fang B, Song YP, Li N, Li J, Han Q, Zhao RC (2009b) Resolution of refractory chronic autoimmune thrombocytopenic purpura following mesenchymal stem cell transplantation: a case report. Transplant Proc 41(5):1827–1830

    Article  Google Scholar 

  • Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic transplants of bone marrow. Transplantation 6(2):230–247

    Google Scholar 

  • Frye CA, Wu X, Patrick CW (2005) Microvascular endothelial cells sustain preadipocyte viability under hypoxic conditions. Vitro Cell Dev Biol Anim 41(5–6):160–164

    Article  Google Scholar 

  • Garcia-Arranz M, Dolores Herreros M, Gonzalez-Gomez C, de la Quintana P, Guadalajara H, Georgiev-Hristov T, Trebol J, Garcia-Olmo D (2016) Treatment of Crohn’s-related rectovaginal fistula with allogeneic expanded-adipose derived stem cells: a phase I–IIa clinical trial. Stem Cells Transl Med 5:1441

    Article  Google Scholar 

  • Garcia-Olmo D, Garcia-Arranz M, Garcia LG, Cuellar ES, Blanco IF, Prianes LA, Montes JA, Pinto FL, Marcos DH, Garcia-Sancho L (2003) Autologous stem cell transplantation for treatment of rectovaginal fistula in perianal Crohn’s disease: a new cell-based therapy. Int J Color Dis 18(5):451–454

    Article  Google Scholar 

  • 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):1416–1423

    Article  Google Scholar 

  • Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M (2009) Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum 52(1):79–86

    Article  Google Scholar 

  • Garcia-Olmo D, Herreros D, De-La-Quintana P, Guadalajara H, Trebol J, Georgiev-Hristov T, Garcia-Arranz M (2010) Adipose-derived stem cells in Crohn’s rectovaginal fistula. Case Rep Med 2010:961758

    Article  Google Scholar 

  • Gimble JM, Guilak F, Bunnell BA (2010) Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells. Stem Cell Res Ther 1(2):19

    Article  Google Scholar 

  • Gimble JM, Bunnell BA, Guilak F (2012) Human adipose-derived cells: an update on the transition to clinical translation. Regen Med 7(2):225–235

    Article  Google Scholar 

  • Gir P, Oni G, Brown SA, Mojallal A, Rohrich RJ (2012) Human adipose stem cells: current clinical applications. Plast Reconstr Surg 129(6):1277–1290

    Article  Google Scholar 

  • 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):54–63

    Article  Google Scholar 

  • 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–S44

    Article  Google Scholar 

  • Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19(10):1252–1263

    Article  Google Scholar 

  • Junqueira LCUA, Carneiro J (2005) Basic histology: text & atlas. New York, McGraw-Hill Medical Pub. Division

    Book  Google Scholar 

  • Jurgens WJ, Kroeze RJ, Zandieh-Doulabi B, van Dijk A, Renders GA, Smit TH, van Milligen FJ, Ritt MJ, Helder MN (2013) One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect: a pilot study. Biores Open Access 2(4):315–325

    Article  Google Scholar 

  • Kapur SK, Dos-Anjos Vilaboa S, Llull R, Katz AJ (2015) Adipose tissue and stem/progenitor cells: discovery and development. Clin Plast Surg 42(2):155–167

    Article  Google Scholar 

  • Katz AJ, Llull R, Hedrick MH, Futrell JW (1999) Emerging approaches to the tissue engineering of fat. Clin Plast Surg 26(4):587–603. viii

    Google Scholar 

  • Katz AJ, Tholpady A, Tholpady SS, Shang H, Ogle RC (2005) Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. Stem Cells 23(3):412–423

    Article  Google Scholar 

  • Kebriaei P, Robinson S (2011) Treatment of graft-versus-host-disease with mesenchymal stromal cells. Cytotherapy 13(3):262–268

    Article  Google Scholar 

  • Kim M, Kim I, Lee SK, Bang SI, Lim SY (2011) Clinical trial of autologous differentiated adipocytes from stem cells derived from human adipose tissue. Dermatol Surg 37(6):750–759

    Article  Google Scholar 

  • 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. Biomaterials 24(14):2513–2521

    Article  Google Scholar 

  • Kokai LE, Marra K, Rubin JP (2014) Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Transl Res 163(4):399–408

    Article  Google Scholar 

  • Ledford H (2011) Stem-cell scientists grapple with clinics. Nature 474(7353):550

    Article  Google Scholar 

  • Ledford H (2016) Boom in unproven cell therapies intensifies regulatory debate. Nature 537(7619):148

    Article  Google Scholar 

  • Li MD, Atkins H, Bubela T (2014) The global landscape of stem cell clinical trials. Regen Med 9(1):27–39

    Article  Google Scholar 

  • Lindroos B, Suuronen R, Miettinen S (2011) The potential of adipose stem cells in regenerative medicine. Stem Cell Rev and Rep 7(2):269–291

    Google Scholar 

  • Loffler G, Hauner H (1987) Adipose tissue development: the role of precursor cells and adipogenic factors. Part II: the regulation of the adipogenic conversion by hormones and serum factors. Klin Wochenschr 65(17):812–817

    Article  Google Scholar 

  • Mailey B, Saba S, Baker J, Tokin C, Hickey S, Wong R, Wallace AM, Cohen SR (2013) A comparison of cell-enriched fat transfer to conventional fat grafting after aesthetic procedures using a patient satisfaction survey. Ann Plast Surg 70(4):410–415

    Article  Google Scholar 

  • Marx C, Silveira MD, Selbach I, da Silva AS, Braga LM, Camassola M, Nardi NB (2014) Acupoint injection of autologous stromal vascular fraction and allogeneic adipose-derived stem cells to treat hip dysplasia in dogs. Stem Cells Int 2014:391274

    Article  Google Scholar 

  • Matsumoto D, Sato K, Gonda K, Takaki Y, Shigeura T, Sato T, Aiba-Kojima E, Iizuka F, Inoue K, Suga H, Yoshimura K (2006) Cell-assisted lipotransfer: supportive use of human adipose-derived cells for soft tissue augmentation with lipoinjection. Tissue Eng 12(12):3375–3382

    Article  Google Scholar 

  • Minteer DM, Marra KG, Rubin JP (2015) Adipose stem cells: biology, safety, regulation, and regenerative potential. Clin Plast Surg 42(2):169–179

    Article  Google Scholar 

  • Mitchell JB, McIntosh K, Zvonic S, Garrett S, Floyd ZE, Kloster A, Di Halvorsen Y, Storms RW, Goh B, Kilroy G, Wu X, Gimble JM (2006) Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers. Stem Cells 24(2):376–385

    Article  Google Scholar 

  • Nunes SS, Maijub JG, Krishnan L, Ramakrishnan VM, Clayton LR, Williams SK, Hoying JB, Boyd NL (2013) Generation of a functional liver tissue mimic using adipose stromal vascular fraction cell-derived vasculatures. Sci Rep 3:2141

    Article  Google Scholar 

  • Pak J, Lee JH, Park KS, Jeong BC, Lee SH (2016) Regeneration of cartilage in human knee osteoarthritis with autologous adipose tissue-derived stem cells and autologous extracellular matrix. Biores Open Access 5(1):192–200

    Article  Google Scholar 

  • Patrick CW Jr, Chauvin PB, Hobley J, Reece GP (1999) Preadipocyte seeded PLGA scaffolds for adipose tissue engineering. Tissue Eng 5(2):139–151

    Article  Google Scholar 

  • Peltoniemi HH, Salmi A, Miettinen S, Mannerstrom B, Saariniemi K, Mikkonen R, Kuokkanen H, Herold C (2013) Stem cell enrichment does not warrant a higher graft survival in lipofilling of the breast: a prospective comparative study. J Plast Reconstr Aesthet Surg 66(11):1494–1503

    Article  Google Scholar 

  • Petruschke T, Hauner H (1993) Tumor necrosis factor-alpha prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells. J Clin Endocrinol Metab 76(3):742–747

    Google Scholar 

  • Prins HJ, Schulten EA, Ten Bruggenkate CM, Klein-Nulend J, Helder MN (2016) Bone regeneration using the freshly isolated autologous stromal vascular fraction of adipose tissue in combination with calcium phosphate ceramics. Stem Cells Transl Med 5(10):1362–1374

    Article  Google Scholar 

  • Rigotti G, Marchi A, Galie M, Baroni G, Benati D, Krampera M, Pasini A, Sbarbati A (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 1423–1404

    Article  Google Scholar 

  • Riordan NH, Ichim TE, Min WP, Wang H, Solano F, Lara F, Alfaro M, Rodriguez JP, Harman RJ, Patel AN, Murphy MP, Lee RR, Minev B (2009) Non-expanded adipose stromal vascular fraction cell therapy for multiple sclerosis. J Transl Med 7:29

    Article  Google Scholar 

  • Rodbell M (1964) Localization of lipoprotein lipase in fat cells of rat adipose tissue. J Biol Chem 239:753–755

    Google Scholar 

  • Saxer F, Scherberich A, Todorov A, Studer P, Miot S, Schreiner S, Guven S, Tchang LA, Haug M, Heberer M, Schaefer DJ, Rikli D, Martin I, Jakob M (2016) Implantation of stromal vascular fraction progenitors at bone fracture sites: from a rat model to a first-in-man study. Stem Cells 34(12):2956–2966

    Article  Google Scholar 

  • Semon JA, Maness C, Zhang X, Sharkey SA, Beuttler MM, Shah FS, Pandey AC, Gimble JM, Zhang S, Scruggs BA, Strong AL, Strong TA, Bunnell BA (2014) Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis. Stem Cell Res Ther 5(1):2

    Article  Google Scholar 

  • Sterodimas A, Huanquipaco JC, de Souza Filho S, Bornia FA, Pitanguy I (2009) Autologous fat transplantation for the treatment of Parry-Romberg syndrome. J Plast Reconstr Aesthet Surg 62(11):e424–e426

    Article  Google Scholar 

  • Tanikawa DY, Aguena M, Bueno DF, Passos-Bueno MR, Alonso N (2013) Fat grafts supplemented with adipose-derived stromal cells in the rehabilitation of patients with craniofacial microsomia. Plast Reconstr Surg 132(1):141–152

    Article  Google Scholar 

  • Teichert-Kuliszewska K, Hamilton BS, Deitel M, Roncari DA (1992) Augmented production of heparin-binding mitogenic proteins by preadipocytes from massively obese persons. J Clin Invest 90(4):1226–1231

    Article  Google Scholar 

  • Thesleff T, Lehtimaki K, Niskakangas T, Mannerstrom B, Miettinen S, Suuronen R, Ohman J (2011) Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction. Neurosurgery 68(6):1535–1540

    Article  Google Scholar 

  • Turner L, Knoepfler P (2016) Selling stem cells in the USA: assessing the direct-to-consumer industry. Cell Stem Cell 19(2):154–157

    Article  Google Scholar 

  • von Heimburg D, Kuberka M, Rendchen R, Hemmrich K, Rau G, Pallua N (2003) Preadipocyte-loaded collagen scaffolds with enlarged pore size for improved soft tissue engineering. Int J Artif Organs 26(12):1064–1076

    Article  Google Scholar 

  • Weissman IL, Shizuru JA (2008) The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood 112(9):3543–3553

    Article  Google Scholar 

  • 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):2582–2591

    Article  Google Scholar 

  • 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. Aesthet Plast Surg 32(1):48–55. discussion 56–47

    Article  Google Scholar 

  • Yoshimura K, Asano Y, Aoi N, Kurita M, Oshima Y, Sato K, Inoue K, Suga H, Eto H, Kato H, Harii K (2010) Progenitor-enriched adipose tissue transplantation as rescue for breast implant complications. Breast J 16(2):169–175

    Article  Google Scholar 

  • Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Adam J. Katz MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

E. Ehanire, T., Katz, A.J. (2018). Challenges and Status of Adipose Cell Therapies: Translation and Commercialization. In: Gimble, J., Marolt, D., Oreffo, R., Redl, H., Wolbank, S. (eds) Cell Engineering and Regeneration. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-319-37076-7_56-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-37076-7_56-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-37076-7

  • Online ISBN: 978-3-319-37076-7

  • eBook Packages: Springer Reference EngineeringReference Module Computer Science and Engineering

Publish with us

Policies and ethics