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Balance macrophage polarization via cell synthesis of apoptotic bodies in hydrogel microspheres

ABSTRACT: Maintaining the homeostasis of immune ecological niches such as macrophages is essential for skin regeneration. In this study, apoptotic bodies (ABs) with intact bioactive substances of ADSC were constructed by biosynthesis. Further, injectable apoptotic bodies-GelMA microspheres (ABs@GMS) were constructed by microfluidics to maintain the homeostasis of the immune ecological niche in trauma, and inhibit the secretion of argininosuccinate synthetase 1 (ASS1) by ABs-induced downregulated JAK/STAT1 signaling pathway. Consequently, the macrophages’ polarization and inflammatory response were balanced in the wound with promoted angiogenesis. This ABs-functionalized microsphere slowly released biosynthetic apoptotic vesicles that expressed C1q, C3b and other surface "eat me" signals. These vesicles can be directly recognized, phagocytosed and degraded by macrophages, and allow scavenger cells to give meaning to cell death. In vitro, ABs@GMS balanced the JAK/STAT signaling pathway in a form of positive communication from dead to living cells via apoptotic vesicles. In vivo, ABs@GMS balanced the polarization of macrophages and increased the expression of α-smooth muscle actin. In conclusion, ABs synthesized by ADSC can balance traumatic immune disorders and restore homeostasis of the wound immune microenvironment, which would be a highly promising material for macrophage-mediated wound repair.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237758 | GEO | 2023/11/30

REPOSITORIES: GEO

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Project description:OBJECTIVE: To assess the safety and efficacy as well as determination of the molecular mechanism of action of topical allogeneic ADSC therapy in the treatment of ulcers in patients with neuropathic diabetic foot. RESEARCH DESIGN AND METHODS: We examined a total of 57 patients with neuropathic diabetic foot in grades IA and IIA according to the University of Texas classification. Finally 23 patients received treatment with standard therapy and fibrin glue (fibrin gel group) and 23 received treatment with standard therapy and ADSC suspended in tissue glue (fibrin gel + ADSC group). The primary outcome was determining the time needed to reduce the wound size by 50% from the initial size in both groups by assessing the wound surface, the evaluation of treatment safety, expressed as the occurrence of any adverse events; the evaluation of symptoms improvement (e.g. pain, itching, etc.) assessed by Visual Analogue Scale (VAS) and analysis of the expression of selected pro-angiogenic and immunomodulatory factors in the wounds treated in both study groups. RESULTS:The ADSC group benefited from the use of stem cells in terms of accelerated wound healing and greater likelihood of complete healing of the wound. In a second week after administration of therapy, the difference between the groups was already statistically significant (p = 0,04). The time to the 50% reduction of the size of the wound in the fibrin gel + ADSC group was significantly shorter (18.9 +/- 2.2 days ) than in the group receiving fibrin gel (39.8 +/- 6.9 days ), p = 0.0035. CONCLUSIONS: The results of the preliminary analysis show that the use of allogeneic ADSCs in the treatment of neuropathic diabetic foot ulcers is a safe method of therapy, which allows to improve the effects of wound healing. Our study indicates also the association of higher expression of selected proteins expression intensifying the healing process through a faster transition to the proliferation phase with a faster reduction in wound area, and long-term efficacy of allogeneic ADSC cells.

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Balance macrophage polarization via cell synthesis of apoptotic bodies in hydrogel microspheres

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