Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway

Abstract

ObjectiveDifficulty in wound healing is one common complication of diabetes mellitus. The study explored whether the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic ulcer wound was enhanced by the activation of the Wnt signaling pathway.MethodsRat diabetic model was established by intraperitoneal injection of Streptozotocin (STZ). hUCMSCs were purified and seeded on the collagen–chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold, which was subsequently implanted into the cutaneous wound of normal and diabetic rats, followed by daily injection of Wnt signaling pathway agonist (Wnt3a) or antagonist (sFRP3) at the edge of the scaffold. Wound healing was checked on days 7, 14, and 21, and the fibrous tissue deposition, capillaries, and epidermal regeneration at the wound were examined by hematoxylin–eosin staining. The hUCMSCs-CCLDADM scaffold was cultured in vitro and treated with Wnt3a or sFRP3, followed by evaluation of cell proliferation, cell proliferation rate, survival status, and altered protein levels in the Wnt signaling pathway using BrdU staining, CCK-8 assay, live/dead staining, and Western blotting, respectively.ResultsOn days 7 and 14 postoperatively, the speed of wound healing was significantly lower in diabetic rats than that in normal control rats. This phenomenon was significantly improved by the activation of the Wnt signaling pathway that also elevated the fibrous protein deposition and the abundance of capillary in the granulation tissue. Conversely, blockade of Wnt signaling slowed the healing of skin wound in diabetic rats. The activation of Wnt signaling pathway promoted the proliferation and differentiation and decreased the apoptosis of hUCMSCs, thereby elevating the number of living hUCMSCs on the CCLDADM scaffold, while the suppression exerted a contrary effect.ConclusionThe activation of the Wnt signaling pathway promotes the healing of diabetic skin wound by the regulation of proliferation and differentiation of hUCMSCs on the CCLDADM scaffold.

Efficacy of alginate‐and chitosan‐based scaffolds on the healing of diabetic skin wounds in animal experimental models and cell studies: A systematic review

“…The articles were excluded because of study design, study topic (not diabetic wound), human studies, or studies not report wound healing as outcome measurements. Finally, 29 21,24‐51 studies that evaluated the effect of chitosan or alginate on diabetic wound healing were included. Figure 1 illustrated the trial selection process.…”

“…Table 1 presented the descriptive characteristics of the included articles. Overall, there were 23 trials 21,24‐30,32‐46 on chitosan, three trials on alginate, 31,47,48 and three trials on the combination of alginate and chitosan 49‐51 . The animal studies were conducted from 2002 and 2019.…”

“…Only one study provided detailed information about how randomization was carried out in the experiment group and control group and adequately reported on the assignment of samples 21 . Twenty‐three studies had insufficient information about how randomization was carried out in the experiment group and control group or provided inadequate report on the assignment of samples 21,24‐26,28‐37,42,44‐48,50,51 . Five studies did not give information about the randomization 27,38‐41 .…”

The effect of allogenic human Wharton's jelly stem cells seeded onto acellular dermal matrix in healing of rat burn wounds

“…Currently, WJSCs have clinical application for a broad scope of diseases . Human Wharton's jelly stem cells (hWJSCs) have properties such as robust proliferation and differentiation, and weak immunogenicity, thereby posing a great potential in the field of regenerative medicine . MSCs can be seeded onto several scaffolds providing a three‐dimensional environment for the MSCs to grow and improve the reconstruction of the injured tissues.…”

“…14 Human Wharton's jelly stem cells (hWJSCs) have properties such as robust proliferation and differentiation, and weak immunogenicity, thereby posing a great potential in the field of regenerative medicine. 15 MSCs can be seeded onto several scaffolds providing a three-dimensional environment for the MSCs to grow and improve the reconstruction of the injured tissues. These scaffolds were shown to possess properties such as porosity, cytocompatibility, biodegradability, surface physicochemical, and biomechanical activities.…”