Effects of Streptozotocin-Induced Diabetes on Proliferation and Differentiation Abilities of Mesenchymal Stem Cells Derived from Subcutaneous and Visceral Adipose Tissues

Abstract

Accumulated evidence indicates that there are intrinsic differences between adipose tissue-derived stem cells (ASCs) obtained from different body fat depots. Here, we compared the proliferation and multipotency of subcutaneous ASCs (SC-ASCs) and epididymal ASCs (ED-ASCs) before and after induction of diabetes by streptozotocin. The adipogenic and osteogenic abilities of rat SC-ASCs and ED-ASCs were evaluated using Oil Red O and Alizarin Red staining, respectively. The expression of adipocyte (PPAR-γ, LPL) and osteoblast (ALP, SPP1) specific mRNAs was evaluated by quantitative real-time PCR. MTT test was used for determination of cell proliferation capacity. The proliferation of SC-ASCs was higher than ED-ASCs, both before and after diabetes induction (P<0.05). Diabetes increased the proliferative capability of SC-ASCs (P<0.05) but not ED-ASCs. Before diabetes, both adipogenic and osteogenic differentiation of SC-ASCs were higher than ED-ASCs (P<0.05). After diabetes, both SC-ASCs and ED-ASCs were able to differentiate into adipocyte and osteoblast, but the levels of differentiation were higher in SC-ASCs than in ED-ASCs (P<0.05). Diabetes decreased the expression of PPAR-γ and LPL, but increased the SPP1 and ALP expression in both SC-ASCs and ED-ASCs. Our data suggested that diabetes increases the proliferation of ASCs but decreases their adipogenic differentiation. Also, SC-ASCs have higher proliferation and differentiation abilities than ED-ASCs in normal and diabetic conditions so can be more preferable for cell therapy.

Preclinical Assessment of the Proliferation Capacity of Gingival and Periodontal Ligament Stem Cells from Diabetic Patients

“…This was in contrast to multiple reports that showed GMSCs to have a higher proliferation compared to PDLSCs [ 29 ][ 32 ][ 33 ][ 34 ]. This pattern of proliferation described in the diabetic patient was in contrast to previous reports that demonstrated that early after the induction of diabetes with streptozotocin, the proliferative capacity of bone marrow-derived stem cells increased [ 23 ]. The inclusion of a greater number of diabetics enrolled in our study in contrast to using diabetes-induced models may help explain this result.…”

“…This is especially true for a disease like diabetes. The majority of mesenchymal stem cells previously studied for therapeutic purposes have been from sources like bone marrow and adipose tissue [ 23 ][ 28 ]. Both, PDLSCs and GSCs demonstrated promising potential for use in tissue regeneration [ 29 ][ 30 ][ 31 ].…”

“…Diabetes-induced in mice was found to alter the intrinsic properties of stem cells and impair their function and their regenerative ability [ 19 ][ 20 ]. Stem cells investigated in these reports were isolated from tissues other than dental tissues like adipose and bone marrow and has provided accumulating evidence that implies differences in proliferation and differentiation abilities between different sources of stem cells [ 18 ][ 20 ][ 21 ][ 22 ][ 23 ]. However, most of these reports have either investigated stem cells from healthy individuals without comparing the results to diabetic individuals or has used diabetic induced models.…”

Adipocyte biology: It is time to upgrade to a new model

“…Clinical treatment of diabetes with insulin is associated with weight gain and increased adiposity (Purnell & Weyer, ), and insulin promotes adipogenesis and lipogenesis in cell culture. However, similar to ASCs from insulin‐resistant individuals, cultured scASCs from rats with streptozotocin‐induced Type 1 (insulin‐dependent) diabetes exhibited a blunted adipogenic response in culture (Ghorbani et al, ), demonstrating that Type 1 diabetes or chronic hyperglycemia may induce fundamental changes in the insulin signaling of ASCs. Of note, the modified insulin analog detemir, which does not affect body weight, was also correspondingly shown to be less adipogenic than standard insulin when added to cultures of human scASCs and omASCs (Cignarelli et al, ).…”

Human periodontal ligament stem cells (hPDLSCs) spontaneously differentiated into myofibroblast to repairer diabetic wounds

“…Myo broblasts derived from other cells have been shown to produce more contractile activity than proto-myo broblasts in the absence of changes in the expression of other contractile proteins [10] .Therefore, a number of studies have attempted to use MSC and other cells as the therapeutic options for diabetic wound repair. Most mesenchymal stem cells used in previous studies for therapeutic purposes were derived from bone marrow and adipose tissue [11] [12] ,However, the di culty of sampling and the degree of damage to the host greatly limit its clinical application. Thus, it makes sense to nd a better source of suitable cells.…”