Adipose-Derived Mesenchymal Stem Cells Reprogram M1 Macrophage Metabolism via PHD2/HIF-1α Pathway in Colitis Mice

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease worldwide. Infiltration of pro-inflammatory macrophages (M1 macrophages) contributes to the occurrence of bowel inflammation. Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic strategy for UC, but the exact mechanism remains unknow yet. Here, we treated DSS-induced colitis mice with adipose‐derived mesenchymal stem cells (ADMSCs) and revealed that ADMSCs alleviated colon inflammation by reducing the infiltration of M1 macrophages. Moreover, ADMSCs exerted this therapeutic effect by inhibiting succinate accumulation, increasing PHD2 to prevent M1 macrophages from overexpressing HIF-1α and thereby reprogramming the glycolytic pathway of M1 macrophages. Meanwhile, the succinate secreted by M1 macrophages triggered ADMSCs to secrete PGE2 in return, which could also shift macrophages from M1 phenotype to M2. Our work demonstrated an immunomodulatory effect of ADMSCs and provided a novel perspective on UC therapy.

NLRP3‐Dependent Crosstalk between Pyroptotic Macrophage and Senescent Cell Orchestrates Trauma‐Induced Heterotopic Ossification During Aberrant Wound Healing

“…However, from literature, we could find that SASP released by senescent cells was capable of educating the non‐committed macrophages to the pro‐inflammatory subtype resembling the classical M1 polarization. [ 40 ] Besides, a previous report also suggested that senescent cells could disable the efferocytosis function of macrophages to enable their coexistence within the tissue milieu. [ 41 ] Therefore, we could propose that crosstalk between senescent cells and pyroptotic macrophages might result in positive feedback and thereby led to delayed and persistent inflammation in the injured wound, which caused an aberrant healing response.…”

Novel potential therapeutic targets of alopecia areata

“…Therefore, injecting autologous fat into the scalp before hair transplantation can enhance blood vessel distribution in the scalp and stimulate hair development ( 94 ). In addition to their potential applications in tissue repair and regeneration, ADSCs have substantial immunomodulatory properties, such as regulating inflammatory or autoimmune diseases, such as arthritis, colitis, and other autoimmune disorders ( 95 – 97 ). Several studies have demonstrated that their internal extracellular vesicles (EVs) play an essential role.…”

“Adipose-derived mesenchymal stem cell therapy for the management of female sexual dysfunction: Literature reviews and study design of a clinical trial”

“…Yang et al, 2021;R. Li et al, 2022;Yuan et al, 2022). M2 macrophages secrete immunosuppressive and anti-inflammatory cytokines IL-10 and TSG-6 to modulate immune reactions and activate tissue repair (Kim and Hematti 2009;Heo, Choi, and Kim 2019;R.…”

“…ASCs can shift macrophages from the M1 phenotype to the M2 phenotype via their secretomes, such as PGE2, IL6, TSG-6, and miR-451 ( Song et al, 2017 ; C.-Y. Yang et al, 2021 ; R. Li et al, 2022 ; Yuan et al, 2022 ). M2 macrophages secrete immunosuppressive and anti-inflammatory cytokines IL-10 and TSG-6 to modulate immune reactions and activate tissue repair ( Kim and Hematti 2009 ; Heo, Choi, and Kim 2019 ; R. Li et al, 2022 ).…”