Sotagliflozin (LX4211) Alleviates Lower Limb Ischemic Reperfusion by Inhibiting Paracrine of Bone Marrow Mesenchymal Stem Cells

2021 ◽  
Vol 11 (12) ◽  
pp. 2357-2366
Author(s):  
Xiaopeng Guo ◽  
Yingsong Liu ◽  
Mingzhu Wei

We aimed to explore the mechanism by how LX4211 affects bone marrow mesenchymal stem cells (BMSCs) during ischemia-reperfusion (I/R). BMSCs were extracted and treated with LX4211 followed by analysis of cell proliferation and migration by CCK-8, Transwell assay and wound healing tests, cell apoptosis and cycle by flow cytometry, exosomes and VEGFA secretion by immunoenzyme-linked adsorption. BMSCs treated with LX4211 or DMSO were administrated into mice with blood perfusion and capillary or arteriolar density was detected. Treatment with LX4211 significantly inhibited BMSCs proliferation, increased apoptosis and activated AMPK/ACC signaling along with reduced the number of exosomes and VEGFA level and impaired physiological functions. In vivo experiments determined that LX4211 alleviated I/R of lower limbs by inhibiting the muscle retention of BMSCs and paracrine. In conclusion, LX4211 treatment can delay the blood recovery of ischemic non-diabetic mice by reducing the proliferation, migration and impairing paracrine of BMSCs.

2022 ◽  
Vol 12 (3) ◽  
pp. 581-587
Author(s):  
Wenxu Rao ◽  
Kang Yin

This study aims at investigating the mechanism underlying bone marrow mesenchymal stem cells (BMSC) function in glioma. Glioma cells were administered with plasmids loading NF-κB siRNA, microRNA (miRNA)-189 inhibitor, or miR-189 mimics for transfection followed by analysis of miR-189 expression by RT-qPCR, cell apoptosis by flow cytometry, cell proliferation by MTT assay,invasion and migration by Transwell assay, inflammatory factors secretion by ELISA as well as proteins expression by western blot. A mouse model of glioma was established to detect the in vivo effect of BMSCs. miR-189 was lowly expressed in glioma cell lines but enriched in BMSCs. When miR-189 was silenced, cell proliferation, invasion and migration were potentiated and apoptosis was decreased, along with enhancement of N-cadherin, Vimentin, MMP-2 and and MMP-9, and decline in Bax, cleaved casepase-3 and cleaved PARP. Silencing of NF-κB reversed the effect of miR-189 inhibitor on cell progression, accompanied with reduction of inflammatory factors. BMSCs treatment effectively promoted miR-189 expression in glioma and inactivated TNF-α/NF-κB signaling, thereby suppressing tumor growth. In conclusion, miR-189 derived from BMSC inhibits glioma progression through regulation of TNF-α/NF-κB signaling pathway.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Bagher Pourheydar ◽  
Sara Soleimani Asl ◽  
Mostafa Azimzadeh ◽  
Adel Rezaei Moghadam ◽  
Asghar Marzban ◽  
...  

Cell therapy is the most advanced treatment of the cerebral ischemia, nowadays. Herein, we discuss the neuroprotective effects of bone marrow mesenchymal stem cells (BMSCs) on rat hippocampal cells following intravenous injection of these cells in an ischemia-reperfusion model. Adult male Wistar rats were divided into 5 groups: control, sham (surgery without blockage of common carotid arteries), ischemia (common carotid arteries were blocked for 30 min prior to reperfusion), vehicle (7 days after ischemia PBS was injected via the tail vein), and treatment (injections of BMSC into the tail veins 7 days after ischemia). We performed neuromuscular and vestibulomotor function tests to assess behavioral function and, finally, brains were subjected to hematoxylin and eosin (H&E), anti-Brdu immunohistochemistry, and TUNEL staining. The ischemia group had severe apoptosis. The group treated with BMSCs had a lower mortality rate and also had significant improvement in functional recovery (P<0.001). Ischemia-reperfusion for 30 min causes damage and extensive neuronal death in the hippocampus, especially in CA1 and CA3 regions, leading to several functional and neurological deficits. In conclusion, intravenous injection of BMSCs can significantly decrease the number of apoptotic neurons and significantly improve functional recovery, which may be a beneficial treatment method for ischemic injuries.


2019 ◽  
Vol 7 (1) ◽  
pp. 362-372 ◽  
Author(s):  
Shuhao Liu ◽  
Yang Liu ◽  
Libo Jiang ◽  
Zheng Li ◽  
Soomin Lee ◽  
...  

BMP-2-induced migration of BMSCs can be inhibited by silencing CDC42 in vitro and in vivo.


2021 ◽  
Author(s):  
meng li ◽  
ning yang ◽  
li hao ◽  
wei zhou ◽  
lei li ◽  
...  

Abstract ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. ConclusionOur research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.


2012 ◽  
Vol 315 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Wei Zhu ◽  
Ling Huang ◽  
Yahong Li ◽  
Xu Zhang ◽  
Jianmei Gu ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tong Wang ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Min-shan Tsai ◽  
Max Harry Weil

Background: In settings of heart failure, infusion of bone marrow mesenchymal stem cells (MSCs) improves myocardial function both in experimental and clinical studies. The mechanism by which MSCs improve myocardial function remains unknown. Hypothesis: MSCs may differentiate into beating myocytes in vivo. The contractility of these cells is comparable with those of myocytes. Methods: A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 350 – 450g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD). One week later, animals were randomized to receive 5×10 6 MSCs marked with PKH26 in phosphate buffer solution (PBS) or as a PBS bolus injection into local infarcted myocardium. Six weeks after the MSCs or PBS injection, the hearts were harvested and digested with collagease type II and single cardiomyocytes were obtained. PKH26 labeled myocytes differentiating from MSCs were observed with a microscope Olympus I×71. The contractility of labeled and unlabeled beating cells in MSCs-treated animals was compared. The contractility of unlabeled myocytes was compared between MSCs-treated and control groups. Result: The beating fluorescent labeled myocytes can be found in MSCs-treated animals [(1.2±0.4) ×10 6 ] and contractility of these cells were the same as that of unlabeled beating myocytes (Table 1 ). The contractility of unlabeled myocytes, however, was significantly better in MSCs-treated animals. Conclusion: MSCs could differentiate into the beating myocytes. However, this may not be the sole mechanism of improved myocardial function. Table 1 Cells contractility (%)


2020 ◽  
Vol 8 (21) ◽  
pp. 4680-4693
Author(s):  
Jirong Yang ◽  
Yumei Xiao ◽  
Zizhao Tang ◽  
Zhaocong Luo ◽  
Dongxiao Li ◽  
...  

The different negatively charged microenvironments of collagen hydrogels affect the protein adsorption, cell morphology, and chondrogenic differentiation of BMSCs in vitro and in vivo.


Sign in / Sign up

Export Citation Format

Share Document