Endothelial differentiation of diabetic adipose-derived stem cells

Policha, Aleksandra; Zhang, Ping; Chang, Lily; Lamb, Kathleen M.; Tulenko, Thomas N.; DiMuzio, Paul

doi:10.1016/j.jss.2014.06.041

Cited by 25 publications

(26 citation statements)

References 28 publications

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“…In the present study, we investigated the isolation of ASC from diabetic patients and the subsequent ability of these cells to survive and proliferate in stress conditions such as hypoxia and hyperglycemia. Our data suggest that diabetes does not significantly affect ASC isolation efficiency and proliferation, as found by Policha et al [37]. Cellular senescence, found in diabetic adipose tissue, did not influence ASC isolation because passage 1 was obtained during the exact same range of time as non-diabetic ASC [20,21].…”

Section: Discussionsupporting

confidence: 73%

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

et al. 2016

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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.

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Section: Discussionsupporting

confidence: 73%

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

et al. 2016

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“…Indeed, our previous lineage tracing suggest that part of the ASCs may be derived from the white adipocytes (Jumabay et al, ). Therefore it is not surprising that the ASCs also have been shown to have altered viability and differentiation potential in diabetes (Ferrer‐Lorente et al, ,), including angiogenic potential (Koci et al, ; Policha et al, ; Rennert et al, ). These reports together with our findings in DFAT cells have implications for pathological changes in WAT due to diabetes, and for the behavior of stem cells prepared from or delivered to diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

“…The reservoir of stem cells in subcutaneous adipose tissue is known to change in diabetes. Adipose‐derived stem cells (ASCs), derived from the stromal vascular fraction, exhibit impaired viability, and differentiation (Ferrer‐Lorente et al, ,), including endothelial cell (EC), and angiogenic differentiation potential (Koci et al, ; Policha et al, ; Rennert et al, ). Diabetes is also known to limit the therapeutic potential of endothelial progenitor cells (EPCs) and bone marrow‐derived progenitor cells (BMPCs) (Tepper et al, ; Fadini et al, ; Li et al, ), and has been proposed to have deleterious effects on stem cells due to oxidative stress (Saki et al, ).…”

mentioning

confidence: 99%

Effect of Diabetes Mellitus on Adipocyte‐Derived Stem Cells in Rat

Jumabay

Moon

Yeerna

et al. 2015

Journal Cellular Physiology

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Diabetes mellitus affects the adipose tissue and mesenchymal stem cells derived from the adipose stroma and other tissues. Previous reports suggest that bone morphogenetic protein (BMP)4 is involved in diabetic complications, at the same time playing an important role in the maintenance of stem cells. In this study, we used rats transgenic for human islet amyloid polypeptide (HIP rats), a model of type 2 diabetes, to study the effect of diabetes on adipocyte-derived stem cells, referred to as dedifferentiated fat (DFAT) cells. Our results show that BMP4 expression in inguinal adipose tissue is significantly increased in HIP rats compared to controls, whereas matrix Gla protein (MGP), an inhibitor of BMP4 is decreased as determined by quantitative PCR and immunofluorescence. In addition, adipose vascularity and expression of multiple endothelial cell markers was increased in the diabetic tissue, visualized by immunofluorescence for endothelial markers. The endothelial markers co-localized with the enhanced BMP4 expression, suggesting that vascular cells play a role BMP4 induction. The DFAT cells are multipotent stem cells derived from white mature adipocytes that undergo endothelial and adipogenic differentiation. DFAT cells prepared from the inguinal adipose tissue in HIP rats exhibited enhanced proliferative capacity compared to wild type. In addition, their ability to undergo both endothelial cell and adipogenic lineage differentiation was enhanced, as well as their response to BMP4, as assessed by lineage marker expression. We conclude that the DFAT cells are affected by diabetic changes and may contribute to the adipose dysfunction in diabetes.

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“…ASC were chosen as cell source because of their stemness, ease of harvest and pro-angiogenic and anti-inflammatory properties [33]. Like other groups [18,22,24,25], we first considered the differentiation of ASC into SMC and EC to reconstruct the three layers of a blood vessel. However, complete and stable differentiation of ASC in vitro is hard to achieve and, in opposition to our goal, it would increase the production time of the substitutes.…”

Section: Discussionmentioning

confidence: 99%

“…This tissue is easily obtained and the extracted stromal vascular fraction contains a large proportion of stem/stromal cells, even in elderly patients with vascular diseases [14]. Many studies have confirmed the adipose-derived stromal cells (ASC) potential for multilineage differentiation as well as their low immunogenicity [15][16][17][18][19]. More recently, ASC have also been investigated in the context of vascular tissue engineering [16,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%