miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4.

BACKGROUND: Aging is one of the key factors that regulate the function of human bone marrow mesenchymal stem cells (hBM-MSCs) and related changes in microRNA (miRNA) expression. However, data reported on aging-related miRNA changes in hBM-MSCs are limited. METHODS: We demonstrated previously that miR-10a is significantly decreased in aged hBM-MSCs and restoration of the miR-10a level attenuated cell senescence and increased the differentiation capacity of aged hBM-MSCs by repressing Krüpple-like factor 4 (KLF4). In the present study, miR-10a was overexpressed or KLF4 was downregulated in old hBM-MSCs by lentiviral transduction. The hypoxia-induced apoptosis, cell survival, and cell paracrine function of aged hBM-MSCs were investigated in vitro. In vivo, miR-10a-overexpressed or KLF4-downregulated old hBM-MSCs were implanted into infarcted mouse hearts after myocardial infarction (MI). The mouse cardiac function of cardiac angiogenesis was measured and cell survival of aged hBM-MSCs was investigated. RESULTS: Through lentivirus-mediated upregulation of miR-10a and downregulation of KLF4 in aged hBM-MSCs in vitro, we revealed that miR-10a decreased hypoxia-induced cell apoptosis and increased cell survival of aged hBM-MSCs by repressing the KLF4-BAX/BCL2 pathway. In vivo, transplantation of miR-10a-overexpressed aged hBM-MSCs promoted implanted stem cell survival and improved cardiac function after MI. Mechanistic studies revealed that overexpression of miR-10a in aged hBM-MSCs activated Akt and stimulated the expression of angiogenic factors, thus increasing angiogenesis in ischemic mouse hearts. CONCLUSIONS: miR-10a rejuvenated aged hBM-MSCs which improved angiogenesis and cardiac function in injured mouse hearts.

[A clinical study on laser peripheral iridoplasty for primary angle-closure glaucoma with positive provocative tests after iridectomy].

OBJECTIVE: To evaluate the therapeutic effects of laser peripheral iridoplasty for primary angle closure glaucoma with positive dark room and prone test after laser peripheral iridectomy. METHODS: A long-term prospective study of 56 eyes (34 cases) with primary angle-closure glaucoma was carried out. The patients presented with positive dark room and prone provocative test after laser peripheral iridectomy, and laser peripheral iridoplasty by Double-Frequency Nd:YAG laser was performed on them. Their extent of goniosynechia was less than 1/2 circumference of the anterior chamber angle. Forty-nine eyes (27 cases) of all those studied were acute angle-closure glaucoma and the other 7 eyes (7 cases) were chronic angle-closure glaucoma. The inferior peripheral anterior chamber depth, anterior chamber angle, the configuration of peripheral iris and intraocular pressure were observed carefully, and the dark room, prone and mydriatic provocative tests were performed. The postoperative follow-up ranged from 1 year to 4 years. RESULTS: The results showed that in all these cases, the peripheral anterior chamber depth was increased, the anterior chamber angle was widened on goniscope and the trabecular meshwork could be visualized widely in static state. All patients did not have ocular hypertension and damage of visual field in the follow up. Mydriatic, dark room and prone provocative tests following laser peripheral iridoplasty were negative. CONCLUSIONS: In some acute angle-closure glaucoma and chronic angle-closure glaucoma patients, the pupillary block is relieved by laser peripheral iridectomy, but provocative tests can also be positive because of the abnormal configuration of the peripheral iris. Pupillary dilation results in peripheral iris bunching, and the surface of the trabecular meshwork can be blocked, hypertension then occurs. But the laser peripheral iridoplasty can improve the shape of the peripheral iris effectively and it can prevent the disease from deteriorating. The goniscopic examination and provocative tests following laser peripheral iridectomy are very important and also effective in detecting this kind of glaucoma.