Bone Marrow–Derived Mesenchymal Stem Cells Enhanced Diabetic Wound Healing through Recruitment of Tissue Regeneration in a Rat Model of Streptozotocin-Induced Diabetes

2011 ◽  
Vol 128 (4) ◽  
pp. 872-880 ◽  
Author(s):  
Yur-Ren Kuo ◽  
Chun-Ting Wang ◽  
Jiin-Tsuey Cheng ◽  
Feng-Sheng Wang ◽  
Yuan-Cheng Chiang ◽  
...  
2018 ◽  
Vol 315 (6) ◽  
pp. C885-C896 ◽  
Author(s):  
Jianming Guo ◽  
Haidi Hu ◽  
Jolanta Gorecka ◽  
Hualong Bai ◽  
Hao He ◽  
...  

We have previously shown that bone marrow-derived mesenchymal stem cells (BMSC) accelerate wound healing in a diabetic mouse model. In this study, we hypothesized that adipose tissue-derived stem cells (ADSC), cells of greater translational potential to human therapy, improve diabetic wound healing to a similar extent as BMSC. In vitro, the characterization and function of murine ADSC and BMSC as well as human diabetic and nondiabetic ADSC were evaluated by flow cytometry, cell viability, and VEGF expression. In vivo, biomimetic collagen scaffolds containing murine ADSC or BMSC were used to treat splinted full-thickness excisional back wounds on diabetic C57BL/6 mice, and human healthy and diabetic ADSC were used to treat back wounds on nude mice. Wound healing was evaluated by wound area, local VEGF-A expression, and count of CD31-positive cells. Delivery of murine ADSC or BMSC accelerated wound healing in diabetic mice to a similar extent, compared with acellular controls ( P < 0.0001). Histological analysis showed similarly increased cellular proliferation ( P < 0.0001), VEGF-A expression ( P = 0.0002), endothelial cell density ( P < 0.0001), numbers of macrophages ( P < 0.0001), and smooth muscle cells ( P < 0.0001) with ADSC and BMSC treatment, compared with controls. Cell survival and migration of ADSC and BMSC within the scaffolds were similar ( P = 0.781). Notch signaling was upregulated to a similar degree by both ADSC and BMSC. Diabetic and nondiabetic human ADSC expressed similar levels of VEGF-A ( P = 0.836) in vitro, as well as in scaffolds ( P = 1.000). Delivery of human diabetic and nondiabetic ADSC enhanced wound healing to a similar extent in a nude mouse wound model. Murine ADSC and BMSC delivered in a biomimetic-collagen scaffold are equivalent at enhancing diabetic wound healing. Human diabetic ADSC are not inferior to nondiabetic ADSC at accelerating wound healing in a nude mouse model. This data suggests that ADSC are a reasonable choice to evaluate for translational therapy in the treatment of human diabetic wounds.


2019 ◽  
Vol 312 (5) ◽  
pp. 325-336 ◽  
Author(s):  
Mona Saheli ◽  
Mohammad Bayat ◽  
Rasoul Ganji ◽  
Farzane Hendudari ◽  
Raziyeh Kheirjou ◽  
...  

2017 ◽  
Vol 49 (10) ◽  
pp. 541-548 ◽  
Author(s):  
Junwang Xu ◽  
Carlos Zgheib ◽  
Maggie M. Hodges ◽  
Robert C. Caskey ◽  
Junyi Hu ◽  
...  

Impaired diabetic wound healing is associated with a dermal extracellular matrix protein profile favoring proteolysis; within the healing diabetic wound, this is represented by an increase in activated matrix metalloproteinase (MMPs). Treatment of diabetic wounds with mesenchymal stem cells (MSCs) has been shown to improve wound healing; however, there has not yet been an assessment of their ability to correct dysregulation of MMPs in diabetic wounds. Furthermore, there has been no prior assessment of the role of microRNA29b (miR-29b), an inhibitory regulatory molecule that targets MMP-9 mRNA. Using in vitro models of fibroblast coculture with MSCs and in vivo murine wound healing models, we tested the hypothesis that MSCs correct dysregulation of MMPs in a microRNA-29b-dependent mechanism. In this study, we first demonstrated that collagen I and III protein content is significantly reduced in diabetic wounds, and treatment with MSCs significantly improves collagen I content in both nondiabetic and diabetic wounds. We then found that MMP-9 gene expression and protein content were significantly upregulated in diabetic wounds, indicating elevated proteolysis. Treatment with MSCs resulted in a decrease in MMP-9 gene expression and protein content level in diabetic wounds 3 and 7 days after wounding. Zymographic analysis indicated that MSC treatment also decreased the amount of activated MMP-9 present in diabetic wounds. Furthermore, miR-29b expression was inversely associated with MMP-9 gene expression; miR-29b expression was decreased in diabetic wounds and diabetic fibroblast. Following treatment of diabetic wounds with MSCs, as well as in diabetic fibroblasts cocultured with MSCs, miR-29b was significantly increased. These findings suggest a potential mechanism through which MSCs enhance diabetic wound healing by improving collagen I content in diabetic wounds through decreasing MMP-9 expression and increasing miR-29b expression.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 639-P
Author(s):  
LE QI ◽  
ALI REZA AHMADI ◽  
JINNY HUANG ◽  
QING LIN ◽  
MELISSA CHEN ◽  
...  

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