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Diabetic cutaneous ulcers often pose considerable challenges in the healing process. These challenges stem from factors including inadequate perfusion of the ulcer's surrounding environment, persistent inflammation, tissue damage and microbial proliferation. The existing standard treatment modalities prove insufficient in fully addressing the complex pathogenesis of these ulcers. As a novel approach, researchers are exploring cellular therapies employing mesenchymal stem cells (MSCs) for the treatment of diabetic skin ulcers. MSCs are readily found in various tissues, including bone marrow, adipose tissue, placenta, amniotic membrane, amniotic fluid and umbilical cord. However, the optimal source of MSCs for effectively treating diabetic skin ulcers remains a topic of ongoing discussion.
We conducted a comprehensive search of Embase, PubMed and Web of Science databases, spanning from their inception to November 2022. Subsequently, we rigorously screened the literature following predetermined inclusion and exclusion criteria and evaluated the quality of the selected studies using the SYRCLE scale. Finally, the included literature underwent analysis, employing the Bayesian school of thought-based R language. To ensure transparency and accountability, we registered this study with PROSPERO's International Systematic Review Prospective Registry, with the Registration ID: CRD42023387421.
We included a total of 11 articles in our analysis, all of which were randomized controlled studies involving 218 animal models. Among these studies, two utilized adipose-derived MSCs, six employed bone marrow-derived MSCs, one utilized amniotic membrane-derived MSCs and three utilized umbilical cord-derived MSCs. Our network meta-analysis results revealed that there were no statistically significant differences in the healing rates of diabetic skin ulcers among MSCs derived from amniotic membrane, adipose tissue, umbilical cord and bone marrow on days 7–8, 10–12 and 12–14. Notably, according to the probability ranking table, the most effective treatment for diabetic wounds was found to be amniotic membrane-derived MSCs.
There was no statistically significant difference in the efficacy of MSCs derived from amniotic membrane, adipose, umbilical cord and bone marrow in the treatment of diabetic skin ulcers during the short-term observation period, and the probability ranking graphs indicate that amniotic membrane-derived MSCs may be the best choice for the treatment of diabetic skin ulcers.
Aimed to clarify the effect of quercetin and its derivatives on wound healing in animal experiments. PubMed, Embase, Science Direct, Web of Science, SinoMed, Vip Journal Integration Platform, China National Knowledge Infrastructure and WanFang databases were searched for animal experiments investigating the effect of quercetin and its derivatives on wound healing to April 2023. The Review Manager 5.4 software was used to conduct meta-analysis. Eighteen studies were enrolled in this article. According to the SYRCLE's RoB tool assessment, these studies exposed relatively low methodological quality. It was shown that animals with cutaneous wound receiving quercetin had faster wound healing in wound closure (%) than the control group. Moreover, the difference in efficacy gradually emerged after third day (WMD = 7.13 [5.52, 8.74]), with a peak reached on the tenth day after wounding (WMD = 19.78 [17.82, 21.74]). Subgroup analysis revealed that quercetin for wound closure (%) was independent of the types of rats and mice, wound area and with or without diabetes. Clear conclusion was also shown regarding the external application of quercetin for wound healing (WMD = 17.77 [11.11, 24.43]). A significant reduction in the distribution of inflammatory cells occurred in the quercetin group. Quercetin could increase blood vessel density (WMD = 1.85 [0.68, −3.02]), fibroblast distribution and collagen fraction. Biochemical indicators, including IL-1β, IL-10, TNF-α, TGF-β, vascular endothelial growth factor (VEGF), hydroxyproline and alpha-smooth muscle actin (α-SMA), had the consistent results. Quercetin and its derivatives could promote the recovery of cutaneous wound in animals, through inhibiting inflammatory response and accelerating angiogenesis, proliferation of fibroblast and collagen deposition.
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