Adipose-Derived Mesenchymal Stem Cells
The evidence that MSCs (mesenchymal stem cells) could be isolated from adipose tissue has resulted in the shared idea that subcutaneous adipose tissue can be regarded as the ideal source of MSCs and as a viable alternative to bone marrow. Indeed, subcutaneous adipose deposits are accessible, abundant, and can be collected in large quantities, thus providing a potential adult stem cell reservoir for each individual.
History of (ADSCs)
Adipose-derived Stem Cells (ADSCs) came under the spotlight in 2001, when first harvesting technique described by Zuk et al, they demonstrated that autologous adipose tissue could be processed to obtain a fibroblast-like cells, also termed processed lipoaspirate (PLA) cells (multi-lineage stem cells population which is isolated from the stromal vascular fraction SVF of adipose tissue, processed from lipoaspirate). These PLA cells, or stem cells, now known as ADSCs. Since that study, thousands of articles have been issued on processed lipoaspirate (PLA) cells using a variety of terminology including; Adipose-Derived Stem Cells (ADSCs), Adipose-Derived Adult Stem Cells(ADAS), Adipose-Derived Mesenchymal Stem Cells (ADMSCs), and Adipose Stroma-Stem Cells (ASCs).
The evidence that MSCs could be isolated from adipose tissue has resulted in the shared idea that subcutaneous adipose tissue can be regarded as the ideal source of MSCs and as a viable alternative to bone marrow.
The subcutaneous adipose deposits are accessible, abundant, and can be collected without harm in large quantities, thus providing a potential adult stem cell reservoir for each individual. Adipocytes constitute almost 90% of adipose tissue volume and nearly 65% of the total cell number.
Advantages of Stem Cells from Fat Tissue
To date, we have obtained stem cells from virtually all over the body, in the hopes of finding ways to avoid the ethical issues associated with embryonic stem cells.
Newer research studies have now looked at the potential to use stem cells sourced from fat as they share many characteristics of bone marrow derived mesenchymal stem cells (Bm-SCs), Adipose-derived stem cells (ADSCs) are mesenchymal stem cells (MSCs) within the stromal vascular fraction (SVF) of subcutaneous adipose tissue.
- Fat is very rich source of stem cells and can obtained more easily with a 100-1000 times greater stem cells than BMSCs which mean, 1 stem cell for every 50-normal fat cell compared to bone marrow is 1 for 10,000. For that;
- For that each:
1 gram of fat tissue gives 5000- 1 million of stem cells, but even the 5000 is 500 folds greater than 1 gam of bone marrow.
- Possesses extensive proliferative capacity, about 40- folds greater than Bm-SCs.
May give 100–1000 times greater cellular yield.
- Easy to get with minimal morbidity compared to some of the other methods of stem cells sourcing and, in our practice, many of patients are eager for the harvest of unwanted fat, but, the fat that we get from excised block of fat tissue is much higher than the one in lipoaspirate
- ADSCs are a plastic-adherent, multipotent stem cell population, which display a similar differentiation potential to other MSCs, and the ability to differentiate into cells of several lineages from all three germinal layers.
The discovery that ASCs can readily be expanded and have the capacity to undergo adipogenic, osteogenic, chondrogenic, neurogenic and myogenic differentiation in vitro was a significant milestone in ADSC therapeutic applicability.
2. Safety & efficacy of ADSCs have been established… more genetically stable.
3. In long-term culture,possesses extensive proliferative capacity, about 40- folds greater than bone marrow derived stem cells(Bm-SCs). May give 100–1000 times greater cellular yield.
The ability to isolate, purify, and store ADSCs as well as grow them & differentiate them in culture makes ADSCs the potential therapeutic “magic bullet”, but, has to be used strictly in an autologous manner (from same person body), unlike bone marrow-DSCs.
Factors Influencing ADSCs Characteristics
Identifying the patient characteristics that may influence adipocyte & ADSCs viability and behavior in order to have a greater understanding of how to improve fat graft retention rates. No clinical studies have yet set out to address associations between gender, menopausal status and hormone replacement therapies and ADSC yield. But, Laboratory studies reveal some important data.
Adipose Tissue Type & Donor Anatomical Locations: The search for the ideal donor site for fat harvest is ongoing. Of the ten studies of human ADSCs, only three found any difference in adipocyte behaviour between different sites. Padoin et al. showed that fat from the lower abdomen and medial thighs has higher ADSC yield compared to the upper abdomen, trochanteric region, knees and flanks. Jurgens et al. also reported significantly higher ADSC yield from abdominal aspirate with NO significant differences in differentiation capacity. Geissler et al. reported greater adipocyte viability in lipoaspirates from lower abdomen compared to from flanks and inner thighs, evident only in a subset of younger women (<45 years). There is some evidence to suggest higher ADSC yields from abdominal tissue compared to back and knee among men. However, this difference was not seen among women. This is in agreement with previous studies suggesting that the choice of donor site has little effect on fat graft outcomes. Within the abdomen, fat superficial to the Scarpas layer displays increased multipotency and stem cells features compared to a deep abdominal depot (<45) There is some evidence to suggest higher ADSC yields from abdominal tissue compared to back & knee among men. However, this difference was not seen among women. This is in agreement with previous studies suggesting that the choice of donor site has little effect on fat graft outcomes. Within the abdomen, fat superficial to the Scarpa’s layer displays increased multipotency and stem cells features compared to a deep abdominal depot.
Age: The younger patients demonstrated significantly higher cell proliferation rates & higher lipolysis activity. With an aging population, fat transfer procedures, particularly for regenerative properties, are becoming more relevant. Age-related changes in fat tissue inflammatory profiles resemble those in obesity, in which senescent stem cells & endothelial cells accumulate along with an increase in circulating pro-inflammatory cytokines, including. This increased cytokine release by ADSCs activates adjacent cells into a pro-inflammatory state, impeding adipogenesis & promoting fat cell lipolysis. Advanced age is known to have detrimental effects on blood & BM-MSCs. However, it is reassuring to know that ADSC yield appears relatively stable across age groups. Although the absolute yield of precursor cells per gram of adipose tissue was reduced in some studies, this can be explained by the initial increase in adipocyte size seen with weight gain. These findings demonstrate the reproducibility of adipose tissue as a consistent & abundant source of ADSCs across a spectrum of ages & BMI values. Unsurprisingly there is evidence to support reduced proliferative and differentiation capacities with increasing age, which is likely related to the decreased susceptibility of precursor cells to respond to extracellular signals. Similarly, increasing BMI, particularly within the obese category (BMI >30 kg/m2), was observed to negatively impact ADSC functional capacities, with implications for their use in cellular therapies & reconstructive surgery.
There is still controversy with regards to what causes aging of mesenchymal stem cells, whether it is related to intrinsic or extrinsic factors, but in all likelihood, both.
Gender: studies of human ADSCs, have so far not shown any difference in ADSC yield and proliferation by gender. Faustini et al.studied 37 males and 88 females and reported that the best donor site among men in terms of yield was the abdomen. Aksu et al. studied abdominoplasty tissue from three males and three females and reported that ADSCs from males showed more effective osteogenic differentiation compared to those from females.
Menopausal status :Geissler et al. reported increased adipocyte viability using lower abdominal fat from younger, presumably pre-menopausal women (<45 years) compared to from older women, suggesting a modulatory role of circulating oestrogen levels. However, information regarding hormonal status or supplements was not gathered.
In contrast No age related or gender significant differences in cell surface marker expression (CD34, CD44, CD54. CD73, CD80, CD90, CD105, CD106, CD166, & STRO-1) and there is little difference between genders in related to surface markers except for STRO-1 which was expressing at higher levels in female relative to male patients. Based on fact that oestrogens upregulate receptor expression on embryonic stem cells and the previously suggested notion that androgens have inhibitory effects and oestrogens a stimulatory effect on MSCs, the possibility was suggested that gender may account for the variability observed (Fossett et al. (2011); Ray et al. (2008).
Read More- References:
- A.A. Salibian, A.D. Widgerow, M. Abrouk, et al., Stem cells in plastic surgery: a review of current clinical and translational applications, Arch. Plast. Surg. 40 (2013) 666e675. Click Here for PDF
- Alt EU, Senst C, Murthy SN, Slakey DP, Dupin CL, Chaffin AE, et al. Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res. 2012;8:215–25. Click here for PDF
- Aksu AE, Rubin JP, Dudas JR, Marra KG. Role of gender and anatomical region on induction of osteogenic differentiation of human adipose-derived stem cells. Ann Plast Surg. 2008;60:306–22 Click here for PDF
- Bills JD, Derderian C, Barker J, Lowe A, Lavery LA, Davis KE. The role of estrogen in the modulation of autologous fat graft outcomes. Plast Reconstr Surg. 2015;135:103e–13e. 62.
- B. Lindroos, R. Suuronen, S. Miettinen, (2011) The potential of adipose stem cells in Regenerative medicine, Stem Cell. Click Here for PDF
- Banyard, A.A. Salibian, A.D. Widgerow, G.R. Evans, (2015) Implications for human adipose-derived stem cells in plastic surgery, J. Cell Mol. Med. 19, 21-30. Click Here for PDF
- Choudhery MS, Badowski M, Muise A, Pierce J, Harris DT. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. J Transl Med. 2014;12:8. Click here for PDF
- Di TG, Cicione C, Visconti G, Isgro MA, Barba M, Di SE, et al. Qualitative and quantitative differences of adipose-derived stromal cells from superficial and deep subcutaneous lipoaspirates: a matter of fat. Cytotherapy. 2015;17:1076–89. Click here for PDF
- D’Ippolito G, Schiller PC, Ricordi C, Roos BA, Howard GA. Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res. 1999;14:1115–22. Click here for PDF
- E. Gonzalez-Rey, M.A. Gonzalez, N. Varela, 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 241e248. Click Here for PDF
- Faustini M, Bucco M, Chlapanidas T, Lucconi G, Marazzi M, Tosca MC, et al. Nonexpanded mesenchymal stem cells for regenerative medicine: yield in stromal vascular fraction from adipose tissues. Tissue Eng Part C Methods. 2010;16:1515–21. Click here for PDF
- Faust IM, Johnson PR, Stern JS, Hirsch J. Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol. 1978;235:E279–86. Click here for PDF
- Fraser JK, Wulur I, Alfonso Z, Hedrick MH (2006) Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 24:150–154 Click Here for PDF
- Geissler PJ, Davis K, Roostaeian J, Unger J, Huang J, Rohrich RJ. Improving fat transfer viability: the role of aging, body mass index, and harvest site. Plast Reconstr Surg. 2014;134:227–32 Click here for PDF
- Harris LJ, Zhang P, Abdollahi H, Tarola NA, DiMatteo C, McIlhenny SE, et al. Availability of adipose-derived stem cells in patients undergoing vascular surgical procedures. J Surg Res. 2010;163:e105–12. Click here for PDF
- Hirsch J, Batchelor B. Adipose tissue cellularity in human obesity. Clin Endocrinol Metab. 1976;5:299–311. Click here for PDF
- H. Mizuno, M. Tobita, A.C. Uysal, (2012) Concise review: adipose-derived stem cells as a novel tool for future regenerative medicine, Stem Cell 30 804e810. Click Here for PDF
- K. Yoshimura, T. Shiguera, D. Matsumoto, et al., (2006) Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates, J. Cell Physiol. 208 Click Here for PDF
Kretlow JD, Jin YQ, Liu W, Zhang WJ, Hong TH, Zhou G, Baggett LS, Mikos AG, Cao Y Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells. BMC Cell Biol.(2008) 9:60 Click here for PDF
- Justesen J, Stenderup K, Eriksen EF, Kassem M. Maintenance of osteoblastic and adipocytic differentiation potential with age and osteoporosis in human marrow stromal cell cultures. Calcif Tissue Int. 2002;71:36–44. Click here for PDF
- Jurgens WJ, Oedayrajsingh-Varma MJ, Helder MN, Zandiehdoulabi B, Schouten TE, Kuik DJ, et al. Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies. Cell Tissue Res. 2008;332:415–26. Click here for PDF
- Karastergiou K, Fried SK, Xie H, Lee MJ, Divoux A, Rosencrantz MA, et al. Distinct developmental signatures of human abdominal and gluteal subcutaneous adipose tissue depots. J Clin Endocrinol Metab. 2013;98:362–71 Click here for PDF
- Li K, Gao J, Zhang Z, Li J, Cha P, Liao Y, et al. Selection of donor site for fat grafting and cell isolation. Aesthetic Plast Surg. 2013;37:153–8.
- Luo S, Hao L, Li X, Yu D, Diao Z, Ren L, et al. Adipose tissue-derived stem cells treated with estradiol enhance survival of autologous fat transplants. Tohoku J Exp Med. 2013;231:101–10. 63. Click here for PDF
- Jian‑Huang Wu, M. L., Yan Liang, Tao Lu, Chun‑Yue Duan. (2016). . Chinese Medical Journal, 129 (13 ), 1592-1599. doi: 10.4103/0366‑184464 Click Here for PDF
- J. Gimble, F. Guilak, (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential, Cytotherapy 5 Click Here for PDF
- L. A. Meza-Zepeda, A. Noer, J.A. Dahl, et al., High-resolution analysis of genetic stability of human adipose tissue stem cells cultured to senescence, J. Cel. Mol. Med. 12 (2008) 553e563. Click Here for PDF
- L. E. Kokai, K. Marra, J.P. Rubin, (2014) Adipose stem cells: biology and clinical applications for tissue repair and regeneration, Trans. Click Here for PDF
- P. A. Zuk, M. Zhu, H. Mizuno, et al., (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies, Tissue Eng. Click Here for PDF
- Mojallal A, Lequeux C, Shipkov C, Duclos A, Braye F, Rohrich R, et al. Influence of age and body mass index on the yield and proliferation capacity of adipose-derived stem cells. Aesthetic Plast Surg. 2011;35:1097–105. Click here for PDF
- Moseley TA, Zhu M, Hedrick MH. Adipose-derived stem and progenitor cells as fillers in plastic and reconstructive surgery. Plast Reconstr Surg. 2006;118:121S–8S. Click here for PDF
- Morin CL, Pagliassotti MJ, Windmiller D, Eckel RH. Adipose tissue-derived tumor necrosis factor-alpha activity is elevated in older rats. J Gerontol A Biol Sci Med Sci. 1997;52:B190–5. 85. Click here for PDF
- Oedayrajsingh-Varma MJ, van Ham SM, Knippenberg M, Helder MN, KleinNulend J, Schouten TE, et al. Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy. 2006;8:166–77 Click here for PDF
- Padoin AV, Braga-Silva J, Martins P, Rezende K, Rezende AR, Grechi B, et al. Sources of processed lipoaspirate cells: influence of donor site on cell concentration. Plast Reconstr Surg. 2008;122:614–8. Click here for PDF
- Rohrich RJ, Sorokin ES, Brown SA. In search of improved fat transfer viability: a quantitative analysis of the role of centrifugation and harvest site. Plast Reconstr Surg. 2004;113:391–5. Click here for PDF
- P. A. Zuk, M. Zhu, P. Ashjian, et al., Human adipose tissue is a source of multipotent stem cells, Mol. Biol. Cell 13 (2002) 4279e4295. Click Here for PDF
- P. A. Zuk, (2008) Tissue engineering craniofacial defects with adult stem cells? Are we ready yet? Pediatr. Res. 63 Click Here for PDF
- P. C. Sachs, M.P. Francis, M. Zhao, et al., (2012) Defining essential stem cell characteristics in adipose-derived stromal cells extracted from distint anatomical sites, Cell Tissue Res. 349 Click Here for PDF
- S. R. Daher, B.H. Johnstone, D.G. Phinney, et al., (2008) Adipose stromal/stem cells: basic and translational advances: the IFATS collection, Stem Cell 26 Click Here for PDF
- Sethe S, Scutt A, Stolzing A. Aging of mesenchymal stem cells. Ageing Res Rev. 2006;5:91–116. 83. Click here for PDF
- Schipper BM, Marra KG, Zhang W, Donnenberg AD, Rubin JP. Regional anatomic and age effects on cell function of human adipose-derived stem cells. Ann Plast Surg. 2008;60:538–44. Click here for PDF
- Starr ME, Evers BM, Saito H. Age-associated increase in cytokine production during systemic inflammation: adipose tissue as a major source of IL-6. J Gerontol A Biol Sci Med Sci. 2009;64:723–30 Click here for PDF
- Trojahn Kolle SF, Oliveri RS, Glovinski PV, Elberg JJ, Fischer-Nielsen A, Drzewiecki KT. Importance of mesenchymal stem cells in autologous fat grafting: a systematic review of existing studies. J Plast Surg Hand Surg. 2012;46:59–68. Click here for PDF
- Ullmann Y, Shoshani O, Fodor A, Ramon Y, Carmi N, Eldor L, et al. Searching for the favorable donor site for fat injection: in vivo study using the nude mice model. Dermatol Surg. 2005;31:1304–7. Click here for PDF
- van Harmelen V, Skurk T, Rohrig K, Lee YM, Halbleib M, Aprath-Husmann I, et al. Effect of BMI and age on adipose tissue cellularity and differentiation capacity in women. Int J Obes Relat Metab Disord. 2003;27:889–95. Click here for PDF
- Van Harmelen V, Rohrig K, Hauner H. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects. Metabolism. 2004;53:632–7 Click here for PDF
- Van Harmelen V, Rohrig K, Hauner H. Comparison of proliferation and differentiation capacity of human adipocyte precursor cells from the omental and subcutaneous adipose tissue depot of obese subjects. Metabolism. 2004;53:632–7. Click here for PDF
- Yoshimura K, Sato K, Aoi N, Kurita M, Hirohi T, Harii K. Cell-assisted lipotransfer for cosmetic breast augmentation: supportive use of adiposederived stem/stromal cells. Aesthetic Plast Surg. 2008;32:48–55. Click here for PDF
- Zhou J, Lu P, Ren H, Zheng Z, Ji J, Liu H, et al. 17beta-estradiol protects human eyelid-derived adipose stem cells against cytotoxicity and increases transplanted cell survival in spinal cord injury. J Cell Mol Med. 2014;18:326–43. Click here for PDF
- Zhang L, Ebenezer PJ, Dasuri K, Fernandez-Kim SO, Francis J, Mariappan N, et al. Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function. Am J Physiol Endocrinol Metab. 2011;301:E599–607 Click here for PDF