ABSTRACT
The immune system, functioning as the body's "defense army", plays a role in surveillance, defense. Any disruptions in immune system can lead to the development of immune-related diseases. Extensive researches have demonstrated the crucial immunoregulatory role of mesenchymal stem cells (MSCs) in these diseases. Of particular interest is the ability to induce somatic cells under specific conditions, generating a new cell type with stem cell characteristics known as induced pluripotent stem cell (iPSC). The differentiation of iPSCs into MSCs, specifically induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), hold promise as a potential solution to the challenges of MSCs, potentially serving as an alternative to traditional drug therapies. Moreover, the products of iMSCs, termed induced pluripotent stem cell-derived mesenchymal stem cell-derived extracellular vesicles (iMSC-EVs), may exhibit functions similar to iMSCs. With the biological advantages of EVs, they have become the focus of "cell-free therapy". Here, we provided a comprehensive summary of the biological impact of iMSCs on immune cells, explored the applications of iMSCs and iMSC-EVs in diseases, and briefly discussed the fundamental characteristics of EVs. Finally, we overviewed the current advantages and challenges associated with iMSCs and iMSC-EVs. It is our hope that this review related to iMSCs and iMSC-EVs will contribute to the development of new approaches for the treatment of diseases.
ABSTRACT
BACKGROUND: Human umbilical cord mesenchymal stem cells-derived extracellular vesicles (hUCMSC-EVs) have potent immunomodulatory properties similar to parent cells. This study investigated the therapeutic effects and immunomodulatory mechanisms of hUCMSC-EVs in an experimental lupus nephritis model. METHODS: The hUCMSC-EVs were isolated by using differential ultracentrifugation. In vivo, the therapeutic effects of hUCMSC-EVs in lupus-prone MRL/lpr mice were investigated, and the mechanisms of treatment were explored according to the abnormal T and B cell responses among both the spleen and kidney. RESULTS: MRL/lpr mice treated with hUCMSC-EVs reduced proteinuria extent, serum creatinine and renal pathological damage; decreased splenic index and serum anti-dsDNA IgG level; and improved survival rate. hUCMSC-EVs lowered the percentage of T helper (Th)1 cells, double-negative T (DNT) cells, and plasma cells among splenocytes; inhibited the infiltration of Th17 cells but promoted regulatory T (Treg) cells in the kidney, followed by a reduction in pro-inflammatory cytokine levels(IFN-γ, IL-2, IL-6, IL-21, and IL-17 A). In addition, hUCMSC-EVs inhibited the activation of STAT3 and down-regulated IL-17 A protein levels in the kidney. CONCLUSION: The results of this study demonstrated that hUCMSC-EVs had therapeutic effects on experimental lupus nephritis (LN) by regulating Th1/Th17/Treg imbalance and inhibiting DNT and plasma cells. Additionally, hUCMSC-EVs inhibited Th17 cell differentiation in kidney by regulating the IL-6/STAT3/IL-17 signal pathway, which might be an important mechanism for alleviating renal injury. Taken together, we demonstrated that hUCMSC-EVs regulating T and B cell immune responses might represent a novel mechanism of hUCMSCs in treating LN, thus providing a new strategy for treating LN.