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.

Microencapsulated VEGF gene-modified hUCMSCs can effectively improve the vascularization of TED and consequently the quality of wound healing.

Nowadays, wound healing delay due to diabetes is considered to be closely related to the accumulation of advanced glycation end products (AGEs). Although mesenchymal stem cells (MSCs) exhibit positive effects on diabetic wound healing, related mechanisms are still not fully elucidated. It has been reported that MSCs can improve the activity of autophagy in injured tissues, thereby playing an important role in wound healing. The autophagy induced by MSCs may be beneficial to diabetic wound healing via removing AGEs, which provide new ideas for clinical treatment of diabetic wounds with the potential of broad application prospects. In this study, the current research situation and application prospect of umbilical cord-derived MSCs on the clearance of AGEs in diabetic wound were reviewed.

The aim of this study was to investigate changes in regional homogeneity (ReHo) and the functional connectivity of the entorhinal cortex (EC) in vascular mild cognitive impairment (VaMCI) and to evaluate the relationships between such changes and neuropsychological measures in VaMCI individuals. In all, 31 patients with VaMCI and 32 normal controls (NCs) underwent rs-fMRI. Differences in whole-brain ReHo and seed-based bilateral EC functional connectivity (EC-FC) were determined. Pearson's correlation was used to evaluate the relationships between regions with significant group differences and different neuropsychological measures. Vascular mild cognitive impairment (VaMCI) patients had lower scores in Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) and higher ones in Activity of Daily Living (ADL) (p < 0.05). Vascular mild cognitive impairment (VaMCI) individuals had significantly lower ReHo in the left cerebellum and right lentiform nucleus than NCs (P < 0.05, TFCE FWE correction). Vascular mild cognitive impairment (VaMCI) subjects showed significant decreases in the FC of the right EC in the right inferior frontal gyrus, right middle frontal gyrus, bilateral pre-central gyrus, and right post-central/superior parietal lobules (P < 0.05, TFCE FWE correction). Significant positive correlations were found between ReHo and MoCA scores for the right lentiform nucleus (r = 0.37, P < 0.05). The right post-central/superior parietal lobules showed a significant positive correlation between right EC-FC and MoCA scores (r = 0.37, P < 0.05). Patterns in ReHo and EC-FC changes in VaMCI patients and their correlations with neuropsychological measures may be a pathophysiological foundation of cognitive impairment, which may aid the early diagnosis of VaMCI.

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