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

Chronic wounds complicated by diabetes are a significant clinical issue, and their occurrence is expected to continue to rise due to an increased prevalence of diabetes mellitus, especially type 2 diabetes. Diabetic wounds frequently lead to nonhealing ulcers, and often eventually result in limb amputation due to the high risk of infection of the chronic wound. Here, we present a tissue-engineered treatment that combines a novel electrochemically deposited collagen wound matrix and human adipose-derived stem cells. The matrix fabrication process is optimized for voltage and time, and the final collagen biomaterial is thoroughly characterized. This collagen material possesses high tensile strength, high porosity, and excellent biocompatibility and cellular proliferation capabilities. Human adipose-derived stem cells were seeded onto the collagen wound matrix and this construct is investigated in a full thickness excisional wound in a mouse model of type 2 diabetes. This novel treatment is shown to stimulate excellent healing and tissue regeneration, resulting in increased granulation tissue formation, epidermal thickness, and overall higher quality tissue reformation. Both the collagen wound matrix alone and collagen wound matrix in combination with adipose derived stem cells appeared to be excellent treatments for diabetic skin wounds, and in the future can also be optimized to treat other injuries such as burns, blast injuries, surgical incisions, and other traumatic injuries.

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Adipose-derived stem cells and their microenvironment (Niche) in type 2 diabetes mellitus

Stem Cell Investigation ◽

10.21037/sci.2019.12.02 ◽

2020 ◽

Vol 7 ◽

pp. 2-2

Author(s):

Karina ◽

Jeanne A. Pawitan ◽

Imam Rosadi

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Stem Cells ◽

Type 2 Diabetes Mellitus ◽

Adipose Derived Stem Cells

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A gelatin/collagen/polycaprolactone scaffold for skin regeneration

PeerJ ◽

10.7717/peerj.6358 ◽

2019 ◽

Vol 7 ◽

pp. e6358 ◽

Cited By ~ 3

Author(s):

Lin-Gwei Wei ◽

Hsin-I Chang ◽

Yiwei Wang ◽

Shan-hui Hsu ◽

Lien-Guo Dai ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Dermal Fibroblasts ◽

Skin Regeneration ◽

Collagen Content ◽

Wound Dressings ◽

Skin Substitute ◽

Epidermal Keratinocytes ◽

Adipose Derived Stem Cells

Background A tissue-engineered skin substitute, based on gelatin (“G”), collagen (“C”), and poly(ε-caprolactone) (PCL; “P”), was developed. Method G/C/P biocomposites were fabricated by impregnation of lyophilized gelatin/collagen (GC) mats with PCL solutions, followed by solvent evaporation. Two different GC:PCL ratios (1:8 and 1:20) were used. Results Differential scanning calorimetry revealed that all G/C/P biocomposites had characteristic melting point of PCL at around 60 °C. Scanning electron microscopy showed that all biocomposites had similar fibrous structures. Good cytocompatibility was present in all G/C/P biocomposites when incubated with primary human epidermal keratinocytes (PHEK), human dermal fibroblasts (PHDF) and human adipose-derived stem cells (ASCs) in vitro. All G/C/P biocomposites exhibited similar cell growth and mechanical characteristics in comparison with C/P biocomposites. G/C/P biocomposites with a lower collagen content showed better cell proliferation than those with a higher collagen content in vitro. Due to reasonable mechanical strength and biocompatibility in vitro, G/C/P with a lower content of collagen and a higher content of PCL (GCLPH) was selected for animal wound healing studies. According to our data, a significant promotion in wound healing and skin regeneration could be observed in GCLPH seeded with adipose-derived stem cells by Gomori’s trichrome staining. Conclusion This study may provide an effective and low-cost wound dressings to assist skin regeneration for clinical use.

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ID: 1080 Adipose-derived stem cells alleviate glucose tolerance in type 2 diabetic mouse

Biomedical Research and Therapy ◽

10.15419/bmrat.v4is.354 ◽

2017 ◽

Vol 4 (S) ◽

pp. 166

Author(s):

Anh Nguyen Tu Bui ◽

Cong Le Thanh Nguyen ◽

Anh Thi Minh Nguyen ◽

Nhat Chau Truong ◽

Ngoc Kim Phan ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Stem Cells ◽

Blood Glucose ◽

Glucose Tolerance ◽

Adipose Derived Stem Cells ◽

Diabetic Mice ◽

Human Ascs ◽

Type 2 Diabetic

Background: Type 2 diabetes (T2D) is the most common form of diabetes and accounts for 90-95% of all existing diabetic cases. The main etiologies of T2D include insulin resistance in target tissues, insufficient secretion of insulin and subsequent decline of pancreatic β-cell function. Recently, many studies have suggested that adipose – derived stem cells (ASCs) were potential to alleviate insulin resistance and hyperglycemia and promote the islets repair. In this study, ASCs were hypothesized that they could have ameliorative effects on type 2 diabetic mice. Methods: Type 2 diabetic mice were induced by a combination of high-fat diet and injection of STZ 100 mg/kg and NA 120 mg/kg. Thereafter, two doses of 106 human ASCs were transplanted 2 week interval into each mouse via the tail vein. The mice were monitored health condition, rate of mortaity, body weight, consumption of food and water, blood glucose level, serum insulin level and histological structure of pancreatic islets. Results: Our results indicated that the ASC-treated mice expressed improved condition in comparision with non-treated diabetic mice. The consumption of food and water as well as the blood glucose level decreased. Simultaneously, ASC transplantation improved the impaired glucose tolerance and insulin tolerance in T2D mice. Besides, the total cholesterol have significantly decreased. Conclusion: it is suggested that human ASCs infusion is safe and effective for type 2 diabetes mellitus in mice regarding the improved glucose metabolism and insulin resistance.

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Dermal fibroblasts cultured from donors with type 2 diabetes mellitus retain an epigenetic memory associated with poor wound healing responses

Scientific Reports ◽

10.1038/s41598-020-80072-z ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Aaiad H. A. Al-Rikabi ◽

Desmond J. Tobin ◽

Kirsten Riches-Suman ◽

M. Julie Thornton

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Wound Healing ◽

Type 2 Diabetes Mellitus ◽

Chronic Wounds ◽

Dermal Fibroblasts ◽

Necrosis Factor Alpha ◽

Tnf Α

AbstractThe prevalence of Type 2 diabetes mellitus (T2DM) is escalating globally. Patients suffer from multiple complications including the development of chronic wounds that can lead to amputation. These wounds are characterised by an inflammatory environment including elevated tumour necrosis factor alpha (TNF-α). Dermal fibroblasts (DF) are critical for effective wound healing, so we sought to establish whether there were any differences in DF cultured from T2DM donors or those without diabetes (ND-DF). ND- and T2DM-DF when cultured similarly in vitro secreted comparable concentrations of TNF-α. Functionally, pre-treatment with TNF-α reduced the proliferation of ND-DF and transiently altered ND-DF morphology; however, T2DM-DF were resistant to these TNF-α induced changes. In contrast, TNF-α inhibited ND- and T2DM-DF migration and matrix metalloprotease expression to the same degree, although T2DM-DF expressed significantly higher levels of tissue inhibitor of metalloproteases (TIMP)-2. Finally, TNF-α significantly increased the secretion of pro-inflammatory cytokines (including CCL2, CXCL1 and SERPINE1) in ND-DF, whilst this effect in T2DM-DF was blunted, presumably due to the tendency to higher baseline pro-inflammatory cytokine expression observed in this cell type. Collectively, these data demonstrate that T2DM-DF exhibit a selective loss of responsiveness to TNF-α, particularly regarding proliferative and secretory functions. This highlights important phenotypic changes in T2DM-DF that may explain the susceptibility to chronic wounds in these patients.

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