Adipose-Derived Mesenchymal Stem Cells
(ADSCs)

     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.

Availability:

  • 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

Characteristic:

  1. 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 therapeuticmagic 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).

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