Impact of Hyperglycemia and Low Oxygen Tension on Adipose-Derived Stem Cells Compared with Dermal Fibroblasts and Keratinocytes: Importance for Wound Healing in Type 2 Diabetes

Abstract

AimAdipose-derived stem cells (ASC) are currently proposed for wound healing in those with type 2 diabetes mellitus (T2DM). Therefore, this study investigated the impact of diabetes on adipose tissue in relation to ASC isolation, proliferation, and growth factor release and the impact of hyperglycemia and low oxygen tension (found in diabetic wounds) on dermal fibroblasts, keratinocytes, and ASC in vitro.MethodsDifferent sequences of hypoxia and hyperglycemia were applied in vitro to ASC from nondiabetic (n = 8) or T2DM patients (n = 4) to study cell survival, proliferation, and growth factor release. Comparisons of dermal fibroblasts (n = 8) and keratinocytes (primary lineage) were made.ResultsNo significant difference of isolation and proliferation capacities was found in ASC from nondiabetic and diabetic humans. Hypoxia and hyperglycemia did not impact cell viability and proliferation. Keratinocyte Growth Factor release was significantly lower in diabetic ASC than in nondiabetic ASC group in each condition, while Vascular Endothelial Growth Factor release was not affected by the diabetic origin. Nondiabetic ASC exposition to hypoxia (0.1% oxygen) combined with hyperglycemia (25mM glucose), resulted in a significant increase in VEGF secretion (+64%, p<0.05) with no deleterious impact on KGF release in comparison to physiological conditions (5% oxygen and 5 mM glucose). Stromal cell-Derived Factor-1α (-93%, p<0.001) and KGF (-20%, p<0.05) secretion by DF decreased in these conditions.ConclusionsA better profile of growth factor secretion (regarding wound healing) was found in vitro for ASC in hyperglycemia coupled with hypoxia in comparison to dermal fibroblasts and keratinocytes. Interestingly, ASC from T2DM donors demonstrated cellular growth rates and survival (in hypoxia and hyperglycemic conditions) similar to those of healthy ASC (from normoglycemic donors); however, KGF secretion was significantly depleted in ASC obtained from T2DM patients. This study demonstrated the impact of diabetes on ASC for regenerative medicine and wound healing.

Factors associated with complex surgical wounds in breast and abdomen: a case-control observational study

“…Fasting glycemia of less than 99 mg/dL, found in this study as a risk factor for complex surgical wound, contradicts the literature where hyperglycemia appears as a factor that induces complications of complex wounds 11 , 33 . However, hyperglycemia is present in as a response to surgical trauma.…”

The dual delivery of KGF and bFGF by collagen membrane to promote skin wound healing

“…Re‐epithelialization is initiated within hours of injury, and bFGF and KGF promote the proliferation of the related cells. KGF directly stimulates keratinocyte migration (Lafosse, Dufeys, Beauloye, Horman, & Dufrane, ; Peplow & Chatterjee, ), whereas bFGF promotes the migration of fibroblasts and stimulates them to produce collagenase (Barrientos, Stojadinovic, Golinko, Brem, & Tomic‐Canic, ), suggesting their complementary roles in accelerating wound closure. Together, bFGF and KGF can also contribute to the rapid accumulation of the desired cells involved in vascularization.…”

Differences in the neovascular potential of thymus versus subcutaneous adipose‐derived stem cells from patients with myocardial ischaemia

“…Although experiments carried out in murine models have corroborated that ASCs from diabetic mice are compromised in their proliferative potential, migration, secretion of angiogenic cytokines, and ability to establish a vascular network (Cianfarani et al, ; Cronk et al, ; Rennert et al, ), subASCs from diabetic patients have shown secretion of VEGF, growth rates, and tubule formation similar to those of subASCs from healthy subjects (Gu, Lee, Kim, Yoon, & Dhong, ; Lafosse, Dufeys, Beauloye, Horman, & Dufrane, ; Policha et al, ). Our results agree with those of these authors, as we similarly observed no significant differences between the subASCs from T2DM patients and the subASCs from the other patients.…”