Regional Anatomic and Age Effects on Cell Function of Human Adipose-Derived Stem Cells

Abstract

Adipose tissue has been shown to contain adult mesenchymal stem cells that have therapeutic applications in regenerative medicine. There is evidence that the ability of adipose precursor cells to grow and differentiate varies among fat depots and changes with age. Defining these variations in cell function and molecular mechanisms of adipogenesis will facilitate the development of cellbased therapies. We compared cells harvested from 5 different subcutaneous (SC) adipose depots in 12 female patients classified into 3 age ranges (25-30, 40-45, and 55-60 years old). Capacity for differentiation of isolated adipose-derived stem cells (ASCs) with and without ciglitazone, a strong peroxisome proliferatoractivated receptors (PPAR)-γ agonist, was assessed in vitro. ASCs were also characterized by lipolytic function, proliferation, and sensitivity to apoptosis. Additionally, PPAR-γ-2 protein expression was determined. We observed a difference in the apoptotic susceptibility of ASCs from various SC depots, with the superficial abdominal depot (above Scarpas layer) significantly more resistant to apoptosis when compared with the 4 other depots. We have also demonstrated that a PPAR-γ agonist aids in the induction of differentiation in cells from all depots and ages. Although sensitivity to apoptosis was linked to anatomic depot, differences in cell proliferation were related primarily to age. Stimulated free glycerol release has been shown to be highest in the arm depot. The arm depot has also consistently shown expression of PPAR-γ-2 with and without a PPAR-γ agonist. Younger patients have increased PPAR-γ-2 expression in all depots, whereas the older patients have consistent elevated expression only in the arm and thigh depots. We have shown there is variability in function of ASCs that have been harvested from different SC depots. Additionally, we have shown age-related changes in function. These data will help select patients and cell harvest sites most suitable for tissue engineering therapies.

Comparison of the Viability and Yield of Adipose-Derived Stem Cells (ASCs) from Different Donor Areas

“…Adipose tissue from the abdomen, waist, thigh and inner knee revealed no significant differences with regard to the viability profile of cells. Superficial abdominal depot has also been shown to less susceptible to apoptosis compared to ASCs from other regions (20). However, we did not observe significant differences in viability profiles among donor areas.…”

“…It has been shown that ASCs from younger patients hold a greater proliferative capacity and are more efficient in differentiating into mature adipocytes than those from older patients (20), rendering younger patients more suitable for tissue engineering applications. In the present study, the mean age was 41.5 years, significantly less than the age group of 55-60 that displays the highest apoptotic rates (20).…”

Concise Review: Adipose-Derived Stromal Vascular Fraction Cells and Stem Cells: Let's Not Get Lost in Translation

“…While an analysis of breast tissues specimens from >180 women donors aged 16-73 did not observe an age dependent difference in stromal cell numbers or adipogenesis, increased body mass index correlated significantly with reduce cell numbers and differentiation [9]. Clinical studies examining subcutaneous adipose tissue from 12 to 52 donors have reported reduced ASC adipogenesis, angiogenesis, osteogenesis, and/or proliferative capacity as a function of advancing donor age [10][11][12]. Similarly, a detailed comparison of five different subcutaneous depots determined that ASC isolated from the arm and thigh best maintained adipogenic potential as a function of advancing age [12].…”

“…Clinical studies examining subcutaneous adipose tissue from 12 to 52 donors have reported reduced ASC adipogenesis, angiogenesis, osteogenesis, and/or proliferative capacity as a function of advancing donor age [10][11][12]. Similarly, a detailed comparison of five different subcutaneous depots determined that ASC isolated from the arm and thigh best maintained adipogenic potential as a function of advancing age [12]. Further studies in larger cohorts will be necessary before patient demographics can be used to predict the functionality and recovery of SVF cells and ASCs from donors as well as the relative utility of specific depot sites.…”

Adult Gland Derived Stem Cells (Gdscs); Potentials, Hurdles and Expectations

“…In contrast to HSCs, MSCs can be grown more easily and can differentiate into mesoderm-derived tissues, while HSCs can re-constitute the haemopoeitic system. MSCs can be selectively grown into bone cells (osteocytes) [8], fat cells (adipocytes) [9] and cartilage cells (chondrocytes) [10] which made them an attractive choice for bone and cartilage tissue engineering as autologous transplants [11,12]. Moreover, they are now considered a routine medical procedure in treating leukemia patients in addition to HSCs [13].…”