AB-08

Psoriasis, a chronic inflammatory skin disease, is a refractory disorder. Previous studies have shown that the imbalance of the T‐helper (Th)17/regulatory T cells (Treg) results in the immune imbalance of T cells in psoriatic patients, and that mesenchymal stem cells display an immunosuppressive role by promoting the differentiation of T cells into Treg, leading to a reduction in the proportion of Th17/Treg. Utility of mesenchymal stem cells is becoming a new approach for the treatment of immune disorders. Following co‐culture of dermal mesenchymal stromal cells (DMSC) and CD3+ T cells with or without transforming growth factor (TGF)‐β receptor inhibitor, the biological function and relative signal pathway of CD3+ T cells were assessed by flow cytometry, transwell, real‐time polymerase chain reaction and western blotting, respectively. Normal DMSC were more potent than psoriatic DMSC in inhibition of CD3+ T‐cell proliferation, and stimulation of CD3+ T‐cell apoptosis than psoriasis DMSC. Moreover, normal DMSC decreased the ratio of Th17/Treg, while enhancing the immunosuppressive effect of Tregs on effector T cells. However, TGF‐β receptor (TGF‐βR) inhibitor attenuated the effect of normal DMSC on CD3+ T cells and Th17/Treg ratio. Additionally, the normal DMSC were more potent than the psoriatic DMSC in increasing TGF‐β receptors and activation of TGF‐β/SMAD pathway in psoriatic CD3+ T cells. In conclusion, normal DMSC can partially improve the biological function and immunosuppressive ability of psoriatic CD3+ T cells, possibly via upregulating the TGF‐β receptors.

Fibroblasts are crucial for supporting normal wound healing. However, the functional state of these cells is impaired in diabetics because of a high-glucose (HG) microenvironment. Small extracellular vesicles (sEVs) have emerged as a promising tool for skin wound treatment. The aim of this study was to investigate the effects of sEVs derived from human decidua-derived mesenchymal stem cells (dMSC-sEVs) on HG-induced human dermal fibroblast (HDF) senescence and diabetic wound healing and explore the underlying mechanism.

We first created a HDF senescent model induced by HG in vitro. dMSC-conditioned medium (dMSC-CM) and dMSC-sEVs were collected and applied to treat the HG-induced HDFs. We then examined the proliferation, migration, differentiation, and senescence of these fibroblasts. At the same time, the expressions of RAGE, p21 RAS, Smad2/3, and pSmad2/3 were also analyzed. Furthermore, pSmad2/3 inhibitor (SB431542) was used to block the expression of pSmad2/3 to determine whether dMSC-sEVs improved HDF senescence by activating Smad pathway. Finally, we assessed the effect of dMSC-sEVs on diabetic wound healing.

The HG microenvironment impaired the proliferation, migration, and differentiation abilities of the HDFs and accelerated their senescence. dMSC-CM containing sEVs improved the proliferation and migration abilities of the HG-induced fibroblasts. dMSC-sEVs internalized by HG-induced HDFs not only significantly promoted HDF proliferation, migration, and differentiation, but also improved the senescent state. Furthermore, dMSC-sEVs inhibited the expression of RAGE and stimulated the activation of Smad signaling pathway in these cells. However, SB431542 (pSmad2/3 inhibitor) could partially alleviate the anti-senescent effects of dMSC-sEVs on HG-induced HDFs. Moreover, the local application of dMSC-sEVs accelerated collagen deposition and led to enhanced wound healing in diabetic mice. The detection of PCNA, CXCR4, α-SMA, and p21 showed that dMSC-sEVs could enhance HDF proliferation, migration, and differentiation abilities and improve HDF senescent state in vivo.

dMSC-sEVs have regenerative and protective effects on HG-induced senescent fibroblasts by suppressing RAGE pathway and activating Smad pathway, thereby accelerating diabetic wound healing. This indicates that dMSC-sEVs may be a promising candidate for diabetic wound treatment.