چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| هانیه صالحی پورمهر | دوم |
| سکینه حاج ابراهیمی | اول |
| لیلا روشنگر | چهارم |
| رضا رهبرقاضی | سوم |
| جواد محمودی | پنجم |
| کریستوفر چپل | ششم |
| نسرین ابوالحسن پور | هفتم |
| عنوان | متن |
|---|---|
| کلمات کلیدی | |
| خلاصه مقاله | Introduction Employment of mesenchymal stem cells (MSCs) therapy represents an emergent strategy in neuro-urology field. Although this approach holds promise for management of neurogenic bladder (NGB), issues such as suitable sources and administration route of these cells as well as possible unknown side effects need more investigations. Here, we aimed to investigate whether intra bladder wall autologous bone marrow mesenchymal SC (BM-MSCs) transplantation, as a minimally invasive method, could able to improve NGB following SCI model in female rats. Study design, materials and methods Experiments were approved by the local ethical committee of animal care and use (IR.TBZMED.REC.1395.24). A total of adult 42 female Wistar rats (weighing 220-260 g) were divided into 6 groups (n = 7 in each) as below; control, sham operated (sham), complete transection SCI (cSCI), hemisection SCI (hSCI), cSCI + BM-MSCs (cSCI + MSCs) and hSCI + BM-MSCs (hSCI + MSCs) groups. Control group didn’t receive any intervention, rats in sham group underwent T9 laminectomy by a posterior midline approach without spinal cord damage; cSCI and hSCI rats underwent T9 transection and hemisection of the spinal cord, respectively and then received a single injection of normal saline into bladder wall 4 weeks post injury. Animals in cSCI + MSCs and hSCI + MSCs groups received 1×106/120µl injection of BM - MSCs into bladder wall, 4 weeks post injury. Urodynamics study was used to evaluate changes in bladder function in study groups 4 weeks post cell transplantation (Fig.1.). Also, molecular assessments including apoptotic cell death monitoring and differentiation of the injected BM-MSCs to smooth muscle were done at the end of experiment. Results As urodynamics study findings showed cSCI and hSCI resulted in hyperreflexic bladders, while BM-MSCs transplantation only was able to reduce the amplitude of the uninhibited contraction cSCI + MSC. Furthermore, the compliance and residual volume only were recovered in the hSCI + MSCs group. Data showed that collagen deposition was markedly increased in the SCI group compared to the control or sham groups. These changes were decreased post-treatment in the hSCI group (p<0.05) (Fig.2.). The number of apoptotic (TUNEL positive cells) was increased after SCI induction in bladder tissue. In contrast, transplantation of the BM-MSCs decreased the number of TUNEL-positive cells in the SCI-induced rats. However, only in hSCI-MSC group it was statistically significant (Fig.3.). In the present study, c-Fos expression was increased after SCI in the bladder and spinal cord. It can be inferred that dysfunction of the nerve connection caused by SCI might strongly stimulate the micturition-related neuronal voiding centers in the brain. Expressions of c-Fos was suppressed by transplantation of the BM-MSCs. In our study, endogenous BDNF levels in the spinal cord were unchanged after BM-MSCs transplantation (Fig.4.). Increment of Ki67 expression represented enhancement of proliferating cells, which is relevant to the facilitation of tissue repair. In the present study, we evaluated the expression of Ki67 in the bladder tissues. The results of our study showed that after SCI induction Ki67 expression was increased significantly in bladder tissue. However, after cell transplantation it decreased. In the treated groups with BM-MSCs, transplanted cells expressing immunoreactivity against SMA were found, indicating that BM-MSCs differentiated into smooth muscle cells. The merged cells expressing yellow fluorescence was doubly positive for human mitochondria antigen and SMA, indicating that they were from BM-MSCs Conclusion Neuro-regeneration in stem cell therapy to correct bladder dysfunction is a logical and promising strategy. According to the data from our study, the administration of stem cells could repair SCI-induced NGB by engaging various cellular mechanisms such as the promotion of cellular dynamics and differentiation into various lineages. Our study added a notion that urinary dysfunction associated with SCI was improved following direct injection of autologous BM-MSC transplantation to bladder wall in the chronic phase of SCI injury. |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| 11.1.pdf | 1399/05/31 | 219823 | دانلود |
| 11.pdf | 1399/05/31 | 1158886 | دانلود |
