Paracrine effects of adipose-derived stem cells in cutaneous wound healing in streptozotocin-induced diabetic rats

Abstract

Objective: The purpose of this study was to explore the paracrine effects of adipose-derived stem cells (ASCs) on cutaneous wound healing in diabetic rats Method: The ASCs were isolated and identified by immunofluorescent staining. The ASCs-conditioned medium (ASCs-CM) was harvested. Cell counting kit (CCK)-8 assay, scratch experiments, western blot and quantitative polymerase chain reaction (qPCR) were performed to observe the effects of ASCs-CM on fibroblasts. A full-thickness skin wound diabetic rat model was prepared, using 34 male, Sprague Dawley rats. ASCs-CM or negative-control medium (N-CM) was injected around the wound surface. The existing wound area was measured on days 4, 8, 12 and 16 after the postoperative day, and the wound tissues were collected for immunohistochemical staining and qPCR quantitative study. Results: In this experiment, the isolated cells were characterised as ASCs. The results of CCK-8 assay, cell scratch test, western blot and qPCR showed ASCs-CM could significantly promote the proliferation, migration and differentiation of fibroblasts. Simultaneously, the healing rate of full-thickness skin wounds in diabetic rats was significantly higher in the ASCs-CM group than the N-CM group on days 4, 8, 12 and 16. Immunohistochemical staining and qPCR results showed that the expression of vascular endothelial growth factor (VEGF, days 4 and 8), α-smooth muscle actin (SMA) (days 4 and 16), transforming growth factor (TGF)-β1 (days 4, 8 and 12) were higher in the ASCs-CM group than that of the N-CM group (p<0.05). Conclusion: This experiment demonstrated that ASCs-CM may accelerate wound healing in diabetic rats by promoting the secretion of TGF-β1, VEGF and the proliferation, migration and differentiation of fibroblasts.

Dual CXCR4/IL-10 Gene-Edited Human Amniotic Mesenchymal Stem Cells Exhibit Robust Therapeutic Properties in Chronic Wound Healing

“…Recent findings demonstrate that stem cells have therapeutic capacity in healing chronic wounds [ 2 ]. Mesenchymal stem cells (MSCs), endothelial progenitor cells, and hematopoietic stem cells are involved in the wound healing process via direct or indirect mechanisms, such as transdifferentiation, re-epithelialization, paracrine actions, and remodeling of the extracellular matrix [ 3 , 4 , 5 ]. However, there are some controversies regarding the efficacy of stem cells in clinical trials [ 6 ].…”

Sodium alginate/gelatin hydrogels loaded with adipose‐derived mesenchymal stem cells promote wound healing in diabetic rats

“…32 ASC-conditioned medium can promote diabetic wound healing through increasing TGF-β1 secretion. 29 Consistently, TGF-β1, a key wound healing growth factor, is upregulated in wounds treated with ASCs loaded in Pluronic F-127 hydrogels. 21 We found that IL-6 levels decreased, macrophage polarization and promote angiogenesis to accelerate diabetic wound healing.…”

“…The combination of acupuncture and stem cell‐seeded cryogel/hydrogel biomaterials on wounds produces immunomodulatory effects, partially mediated by the reduced expression of proinflammatory cytokines (IL‐1β and TNF‐α) 32 . ASC‐conditioned medium can promote diabetic wound healing through increasing TGF‐β1 secretion 29 . Consistently, TGF‐β1, a key wound healing growth factor, is upregulated in wounds treated with ASCs loaded in Pluronic F‐127 hydrogels 21 .…”

“…28 ASC-conditioned medium could promote the secretion of VEGF to facilitate wound healing in diabetic rats. 29 Moreover, key angiogenesis growth factors, including VEGF were upregulated in wounds treated with ASCs loaded in Pluronic F-127 hydrogels. 21 Here, VEGF, PDGF and EGF levels increased in both the Gel-Al/ASCs combination and Gel-Al alone groups, most notably in the Gel-Al/ASCs combination group.…”

“…Co‐cultures of ASCs and DAT increased the secretion of local growth factors, including platelet‐derived growth factor (PDGF), VEGF, and EGF, 27 all of which are involved in angiogenesis 28 . ASC‐conditioned medium could promote the secretion of VEGF to facilitate wound healing in diabetic rats 29 . Moreover, key angiogenesis growth factors, including VEGF were upregulated in wounds treated with ASCs loaded in Pluronic F‐127 hydrogels 21 .…”