RESUMO
Mesenchymal stromal cells (MSCs) are a heterogeneous population of adult stem cells, which are multipotent and possess the ability to differentiate/transdifferentiate into mesodermal and nonmesodermal cell lineages. MSCs display broad immunomodulatory properties since they are capable of secreting growth factors and chemotactic cytokines. Safety, accessibility, and isolation from patients without ethical concern make MSCs valuable sources for cell therapy approaches in autoimmune, inflammatory, and degenerative diseases. Many studies have been conducted on the application of MSCs as a new therapy, but it seems that a low percentage of them is related to clinical trials, especially completed clinical trials. Considering the importance of clinical trials to develop this type of therapy as a new treatment, the current paper is aimed at describing characteristics of MSCs and reviewing relevant clinical studies registered on the NIH database during 2016-2020 to discuss recent advances on MSC-based therapeutic approaches being used in different diseases.
RESUMO
BACKGROUND: Alzheimer's disease (AD) is one of the most common NDs leading to cognitive dysfunctions and dementia which are progressively worsen with age. Cell therapy is currently of particular interest in treatment of neurodegenerative disease (ND) such as AD. However, the effective treatment for AD is yet to be found. OBJECTIVE: In this study, the possible roles of human umbilical mesnchymal stromal cord (hUMSCs) and adipose mesenchymal stem cells (hAD-MSCs) in neurogenesis and synaptic function were investigated using a ß-amyloid 1-42 (ß A42)-induced AD rat model. METHODS: hUMSCs and hAD-MSCs were isolated from umbilical cord stroma and adipose tissue, respectively. The expression of Mesenchymal (CD73, CD90 and CD105) and hematopoietic (CD45 and CD133) markers of hUMSCs and hAD-MSCs were confirmed by flow cytometry. Alzheimer's rat model was created by ß-amyloid 1-42 injection into the hippocampus and confirmed by Morris Water Maze and immunohistochemical staining. hUMSCs and hAD-MSCs were injected in Alzheimer's rat model, intravenously. Deposition of ß-amyloid in the CA1 of hippocampus was assayed 3 months after cell administration. The expression of synaptophysin and GAP43 proteins was assessed by Western blot. Neural death was assessed by Nissl staining. RESULTS: The data obtained from flow cytometry showed that surface mesenchymal and hematopoteic markers of the fibroblastic like cells isolated from adipose tissue and umbilical cord were expressed highly in hUMSCs and mostly in hAD-SCs. Transplantation of MSCs reduced ß-amyloid deposition in the hippocampus of the AD rats compared to the ß-amyloid group. The rate of neuronal cell death in the hippocampus of the ß-amyloid-treated rats was significantly increased compared to that of the control group. The percentage of apoptotic cells in this group was 72.98 ± 1.25, which was significantly increased compared to the control group. Transplantation of either hUMSCs or hAD-SCs, respectively, resulted in a significant reduction in the apoptotic rate of the neuronal cells in the hippocampus by 39.47 ± 0.01 (p = 0.0001) and 43.23 ± 0.577 (p = 0.001) compared to the ß-amyloid group. MSC transplantation resulted in a significant up-regulation in the expression levels of both synaptogenic (synaptophysin) and neurogenic markers (GAP43) by 1.289 ± 0.112 (P = 0.02) and 1.112 ± 0.106 (P = 0.005) fold in the hUMSCs-treated group and 1.174 ± 0.105 (P = 0.04) and 0.978 ± 0.167 (P = 0.008) fold in the hAD-SCs-treated group, respectively. CONCLUSION: Intravenous injection of hUMSCs and hAD-MSCs is a safe approach that improves synaptic function and neurogenesis via up-regulation of synaptophysin and GAP43 protein expression levels, respectively, in Alzheimer's model. Intravenous injection of both applied SCs could improve learning and cognitive impairment induced by ß A42 injection.
RESUMO
Background: A wide variety of cytokines are released from human amniotic membrane cells (hAMCs), which can increase the rate of differentiation of mesenchymal stem cells into the neurons. We studied the effect of Retinoic Acid (RA) on the differentiation rate of human Umbilical Cord Mesenchymal Stem Cells (hUMSCs) which were co-cultured with hAMCs. Methods: In this experimental study, both hUMSCs and hAMCs were isolated from postpartum human umbilical cords and placenta respectively. The expression of mesenchymal (CD73, CD90 and CD105), hematopoietic and endothelial (CD34 and CD45) markers in hUMSCs were confirmed by flow cytometry. The hUMSCs were cultured in four distinct groups: group 1) Control, group 2) Co-culture with hAMCs, group 3) RA treatment and group 4) Co-culture with hAMCs treated by RA. Twelve days after culturing, the expression of NSE, MAP2 and ChAT differentiation genes and their related proteins were examined by real-time PCR and immunocytochemistry respectively. Results: The flow-cytometry analysis indicated increased expression of mesenchymal markers and a low expression of both hematopoietic and endothelial markers (CD73:98.24%, CD90: 97.32%, CD105: 90.75%, CD34: 2.96%, and CD45:1.74%). Moreover, the expression of both NSE and MAP2 markers was increased significantly in all studied groups in comparison to the control group On the other hand, the expression of ChAT had a significant increase in the group 2 and 4 (RA and RA+ co-culture). Conclusion: RA can be used as an effective inducer to differentiate hUMSCs into cholinergic-like cells, and hAMCs could increase the number of differentiated cells as an effective factor.
RESUMO
Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks) used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR), vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract). Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (P<0.0001). Our results also revealed that the number of dark neurons significantly increases in ischemia group compared to control group (P<0.0001). Following treatment with Rosa damascene extract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.