Simvastatin improves the homing of BMSCs via the PI3K/AKT/miR‐9 pathway

Abstract

Bone marrow‐derived mesenchymal stem cells (BMSCs) have great therapeutic potential for many diseases. However, the homing of BMSCs to injury sites remains a difficult problem. Recent evidence indicates that simvastatin stimulates AKT phosphorylation, and p‐AKT affects the expression of chemokine (CXC motif) receptor‐4 (CXCR4). Therefore, simvastatin may improve the expression of CXCR4 in BMSCs, and microRNAs (miRs) may participate in this process. In this study, we demonstrated that simvastatin increased both the total and the surface expression of CXCR4 in BMSCs. Stromal cell‐derived factor‐1α (SDF‑1α)‐induced migration of BMSCs was also enhanced by simvastatin, and this action was inhibited by AMD 3100(a chemokine receptor antagonist for CXCR4). The PI3K/AKT pathway was activated by simvastatin in this process, and LY294002 reversed the overexpression of CXCR4 caused by simvastatin. MiR‐9 directly targeted CXCR4 in rat BMSCs, and simvastatin decreased miR‐9 expression. P‐AKT affected the expression of miR‐9; as the phosphorylation of AKT increased, miR‐9 expression decreased. In addition, LY294002 increased miR‐9 expression. Taken together, our results indicated that simvastatin improved the migration of BMSCs via the PI3K/AKT pathway. MiR‐9 also participated in this process, and the phosphorylation of AKT affected miR‐9 expression, suggesting that simvastatin might have beneficial effects in stem cell therapy.

Troxerutin attenuates myocardial cell apoptosis following myocardial ischemia‐reperfusion injury through inhibition of miR‐146a‐5p expression

“…For example, Y. Liu et al () showed that blocking the PI3K–Akt signaling pathway with specific inhibitor LY294002 could decrease the osteogenic inhibitory effect of vaspin as well as the expression level of miR‐34c. Bing et al () suggested that the phosphorylation of AKT affected the expression of miR‐9 expression, while LY294002 increased miR‐9 expression in bone marrow‐derived mesenchymal stem cells. However, our previous study demonstrated that incubating with troxerutin led to the activation of the PI3K–Akt signaling pathway in rat cardiomyocytes.…”

Exosomes derived from human umbilical cord mesenchymal stem cells inhibit vein graft intimal hyperplasia and accelerate reendothelialization by enhancing endothelial function

“…In our previous study, we have found that MSC transplantation after vein grafting can prevent intimal hyperplasia by accelerating reendothelialization in a rat vein graft model [13,14]. This effect was, in part, attributable to MSCs homed to the site of injury and differentiated into an endothelial phenotype to re-establish the endothelial layer.…”

“…All experimental procedures were approved by the Animal Care and Use Committees at Qilu Hospital of Shandong University. The model was carried out using the anastomotic cuff technique as we have described [13,14,17,18]. Briefly, adult Wistar rats were prepared and made intraperitoneal anaesthesia with chloral hydrate.…”

“…The images were recorded at 0 and 24 h after the monolayers were scratched. Cell migration was further assessed using a Boyden chamber as we described previously [13]. HUVECs were seeded in serum-free ECM in Transwell inserts, wherein the bottom chambers contained complete ECM and different concentrations of exosomes.…”

The effects of conditioned media generated by polarized macrophages on the cellular behaviours of bone marrow mesenchymal stem cells

“…Translation of stem cells and other regenerative paradigms from bench to bedside requires an understanding of host responses to outside cellular and/or material transplants [1]. Both in vitro and in vivo conditions can influence the cellular behaviours of cellular materials as well as their therapeutic potential following transplantation [2][3][4]. In particular, innate immune responses to transplant-based strategies, especially those arising from macrophages (Mφs), have received much attention in recent years in fields ranging from tissue engineering to in situ tissue regeneration [5,6].…”