scholarly journals Evaluation of Clinical and Histological Outcomes of Adipose-Derived Mesenchymal Stem Cells in a Rabbit Corneal Alkali Burn Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Diamantis Almaliotis ◽  
Angelos Thomas ◽  
Anastasia Komnenou ◽  
Eleni Gounari ◽  
Stavroula Almpanidou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Histological Analysis ◽  
Control Group ◽  
Subconjunctival Injection ◽  
Corneal Sensation ◽  
Significant Difference ◽  
Phosphate Buffered Saline ◽  
Made In

To assess effects of adipose-derived mesenchymal stem cells (AMSCs) in corneal alkali injuries in an experimental animal model. Twenty white New Zealand rabbits were included in the study. The animal models were randomly divided into 2 groups. Rabbits in the AMSC group ( n = 10 ) received an intrastromal, a subconjunctival injection, and topical instillation of 0.5 ml totally of phosphate-buffered saline (PBS) containing 2 × 10 6 AMSCs. In the control group ( n = 10 ), rabbits received only 0.5 ml of PBS using the same methods. A masked investigator measured the corneal sensation, anterior chamber Inflammation (ACI), and conjunctival congestion. Additionally, a blind histological and immunohistochemical evaluation was made. In the AMSC group, the central corneal sensation was increased whereas ACI and conjunctival congestion were reduced compared to the control group in the 28 days of follow-up ( p < 0.05 ). A statistically significant difference ( p < 0.05 ) was noted between the two groups as recorded in the above parameters. Histological analysis showed that pathological vascularization was markedly reduced in the AMSC group which was consistent with the absence of factor VIII in the immunohistochemistry sections. There is a trend towards improved clinical outcomes including corneal sensation as well as acceleration in the restoration of normal corneal architecture in corneal alkali burns treated with AMSCs, results that support the need for further research in the field.

scholarly journals Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Random Effects ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Significant Difference

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

scholarly journals Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference ◽  
T1 And T2

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.

Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011440
Author(s):  
Jong-Won Chung ◽  
Won Hyuk Chang ◽  
Oh Young Bang ◽  
Gyeong Joon Moon ◽  
Suk Jae Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Controlled Trial ◽  
Outcome Evaluation ◽  
Autologous Serum ◽  
Secondary Outcome ◽  
Control Group ◽  
Link Type ◽  
Significant Difference ◽  
Major Stroke

ObjectiveTo test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.MethodsIn this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.ResultsA total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range, 28–83) years, and mean interval between stroke onset to randomization was 20.2 (range, 5–89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious, treatment-related adverse events.ConclusionsIntravenous application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.Classification of evidenceThis study provides Class III evidence that autologous mesenchymal stem cells do not improve 90-day outcomes in patients with chronic stroke.Trial registrationclinicaltrials.gov Identifier: NCT01716481.

The Reverse Remodeling Effect of Mesenchymal Stem Cells is Independent from the Site of Epimyocardial Cell Transplantation

2013 ◽  
Vol 8 (6) ◽  
pp. 433-439 ◽  
Author(s):  
Mani Arsalan ◽  
Stefan Dhein ◽  
Heike Aupperle ◽  
Ardawan Julian Rastan ◽  
Markus Jan Barten ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sham Group ◽  
Heart Function ◽  
Capillary Density ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Control Group ◽  
Positive Effects ◽  
Significant Difference

Objective The transplantation of mesenchymal stem cells (MSCs) represents a promising approach for treating the ischemic and the nonischemic diseased heart. The positive effects of transplanting these cells could be shown, but the exact mechanisms remain unknown. We evaluated whether the injection site affects the improvement in left ventricular (LV) ejection fraction (EF) and angiogenesis in doxorubicin (Dox)–induced failing hearts. Methods Heart failure was induced in New Zealand white rabbits by doxorubicin treatment, followed by right ventricular MSC transplantation (RV-MSC, n = 6), LV MSC transplantation (LV-MSC, n = 6), sham treatment (sham group, n = 6), or no therapy (Dox group, n = 5). Healthy rabbits were used as control group (n = 8). Cells were isolated after bone marrow aspiration and transplanted locally into the ventricular myocardium. After 4 weeks, cardiac function and capillary density (CD31 staining) were measured. Results The transplantation of MSCs increased the EF significantly (LV-MSC, 39.0% ± 1.4%, and RV-MSC, 39.2% ± 2.6%, vs sham group, 29.8% ± 3.7%; P < 0.001), without significance between the MSC groups ( P = 0.858). Neither the evidence of a transdifferentiation nor any signs of cell engraftment of transplanted cells could be found. The capillary density (capillaries/high-power field) increased in both MSC groups compared with the sham group (LV-MSC by 8.3% ± 3.4%; and RV-MSC, 8.1% ± 2.2%; P < 0.05), without significance between the two MSC groups ( P = 0.927). Conclusions Injection of autologous MSCs in doxorubicin-induced cardiomyopathic rabbit hearts improves EF and enhances angiogenesis. Despite local application, we observed global effects on heart function and capillary density without significant difference between right and LV injection. The paracrine mechanism might be one possible explanation for these findings.

Mesenchymal Stem Cells Vs. Mesenchymal Stem Cells Combined With Cord Blood For Treating Engraftment Failure Following Autologous Hematopoietic Stem Cell Transplantation: A Pilot Prospective Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3693-3693 ◽  
Author(s):  
YiYing Xiong ◽  
Fan Qian ◽  
Fen Huang ◽  
Yu Zhang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Research Funding ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Significant Difference ◽  
Engraftment Failure

Abstract Background Engraftment failure (EF) is a formidable complication after autologous hematopoietic stem cell transplantation (auto-HSCT). Mesenchymal stem cells (MSCs) and cord blood (CB) have been found to support hematopoiesis. Thus, we designed a multicenter randomized clinical trial to investigate the effects and safety of MSCs alone or combined with CB infusion for patients with EF. Methods Twenty-two patients were randomly assigned to receive the treatment with MSCs alone (MSCs group, n=11) or MSCs combined with CB (CB group, n=11). MSCs were administered once every 2 weeks (2 doses were a cycle) in both groups, and single-unit CB was administered at the same day with the first application of MSCs in CB group; After one cycle of treatments (within 28 days), the patients who did not response to MSCs would receive the therapeutic schedule in CB group, and those patients with partial response (PR) in MSCs group and those without complete response (CR) in CB group would continue another cycle of MSCs treatment. If patients did not obtain CR after two cycles of treatments (within 56 days), they would receive other treatments including allogeneic HSCT. Results After the first treatment cycle, the effect rates were not significant difference in MSCs and CB groups (7/11 vs. 9/11, P=0.635), and the median time of hematopoietic reconstruction was 22 (18-28) and 17 (13-22) days, respectively (P=0.036) in MSCs and CB group. There was statistically significant difference regarding neutrophil engraftment, with 17 (range 9-28) and 8 (range 6-14) days respectively (P=0.030), but no difference regarding platelet engraftment, with 21 (range 18-28) and 18 (range 11-21) days respectively (P=0.092) between MSCs and CB groups. After two cycles of treatments, 17 patients obtained CR, 2 PR and 3 NR. CB chimerisms were not detected by short tandem repeat (STR) at +15 and +30 days after CB infusion. None of the patients experienced any adverse events of grade 3/4 with the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0) and acute GVHD or chronic GVHD during the period of study treatment and follow-up. One patient with PR in MSCs group and 1 NR in CB group received allogeneic HSCT at +249 and +273 days after auto-HSCT because of EF and primary disease relapse, respectively. At a median follow-up time of 345 (range 129–784) days post-transplantation, 16 patients remained alive, 3 died of relapse of primary diseases and 1 died of CMV pneumonia following allo-HSCT. None of patients developed EBV-DNA viremia and EBV-associated diseases in two groups. The 2-year overall survival, disease-free survival and tumor relapse post-transplantation were 75.2% (95% CI, 63.2-87.2%), 79.5% (95% CI, 70.1-88.9%) and 20.5% (95% CI, 11.1-29.9%) respectively. Conclusions Our data suggest that ex-vivo-expanded MSCs derived from HLA-mismatched BM alone or combined with unrelated CB are effective to EF after auto-HSCT. CB can facilitate the effect of MSCs to EF. Both two strategies do not result in GVHD or increase the risk of primary diseases relapse in patients with EF. This trial was registered at www.clinicaltrials.govas#NCT01763099. Disclosures: Liu: It was supported by 863 Program (No. 2011AA020105) and National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; It was supported by National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174). : Research Funding.

scholarly journals The Effect of Adipose Tissue-Derived Mesenchymal Stem Cells on Regeneration of Uterine Scars

2017 ◽  
Vol 23 (3) ◽  
pp. 120
Author(s):  
R. Ada Bender ◽  
Aykan Yücel ◽  
Volkan Noyan ◽  
Aylin Gürpınar ◽  
Pınar Atasoy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Control Group ◽  
Optimum Level ◽  
Wound Recovery ◽  
Significant Difference ◽  
Histopathological Effects ◽  
Mesenchyme Stem Cells

<p><strong>OBJECTIVE:</strong> The mesenchymal stem cell application to uterine healing scars may provide better tissue strength.<br /><strong>STUDY DESIGN:</strong> Hysterectomy was performed on rats, and the wound recovery as a result of primary suturing was evaluated as tissue stretching and the positive histopathological effects. The mesenchymal stem cells originating from the adipose tissue were used during the healing period of the wound and would differentiate to mesenchyme-originated cells present in intact tissue for an optimum level of healing.<br /><strong>RESULTS:</strong> The weights of non-incised uterine horns in the control group were found to be significantly higher than the weights of the incised uterine horns (z=2.52, p=0.012). In the experiment group, the weights of the incised uterine horns were found to be significantly higher than the non-incised uterine horns (z=2.527, p=0.012). In the control group, the non-incised uterine horns withstood the stretching test to a higher extent than the incised horns, and a significant difference was found between the stretching values (z=2.51, p=0.012). In the experiment group, the incised uterine horns withstood the stretching tests to a higher extent than the non-incised uterine horns; however, there was no significant difference between the stretching tests (z=1.540, p=0.123).<br /><strong>CONCLUSION:</strong> Adipose tissue-originated mesenchyme stem cells were observed to increase the tissue stretching during wound healing.<br /><br /></p>

scholarly journals Immunolocalization of Steroidogenic Enzymes (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and P450scc) in Rats with Testicular Dysfunction Treated with Mesenchymal Stem Cells-conditioned Medium

2021 ◽  
Vol 11 (3) ◽  
pp. 368-376
Author(s):  
Linda Miftakhul Khasanah ◽  
Teguh Budipitojo ◽  
Yuda Heru Fibrianto
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Leydig Cells ◽  
Hydroxysteroid Dehydrogenase ◽  
Treated Group ◽  
Control Group ◽  
Testicular Dysfunction ◽  
Significant Difference ◽  
Injection Dose

About 60-80 million couples in the world are suffering from infertility disease. Infertility is a major problem in patients coping with chemotherapy. The chemotherapy process can degenerate non-target organs, especially in testes. Infertility in male or testicular dysfunction is caused by the failure of proliferation and differentiation of the spermatogenic cells. Many studies reported that mesenchymal stem cells-conditioned medium promoted regenerative processes. The present study aimed to investigate the effect of mesenchymal stem cells-conditioned medium on the cisplatin-induced testicular dysfunction by examining the immunolocalization of steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and P450scc which are considered as markers of steroid production. All experimental animals were divided into three groups, namely the control group, mesenchymal stem cells-conditioned medium treated group with an injection dose of 0.2 ml/kg body weight (BW, P1), and mesenchymal stem cells-conditioned medium treated group with an injection dose of 0.5 ml/kg BW (P2). Cisplatin was injected into both treated groups to induce testicular dysfunction. The testicular tissues were processed by the paraffin method, then cut to a thickness of 5 µm, followed by immunohistochemical staining. The HSD3B1 immunoreactivities were found only in Leydig cells, and the intensity increased every week after the injection of mesenchymal stem cells-conditioned medium. The variety of weeks and groups was significantly different in the number of immunoreactive cells of HSD3B1. The results indicated a significant difference between one week after the first injection and the one week after the third and fourth injection. The findings showed a significant difference between the treated group with an injection dose of 0.2 ml/kg BW and the control group. The number of immunoreactive cells of HSD3B1 with an injection dose of 0.5 ml/kg BW was greater compared to the group that received an injection dose of 0.2 ml/kg BW. The intensity of HSD3B1 and HSD17B1 increased every week. The p450scc immunoreactive cells were only found in Leydig cells. The intensity of positive cells of p450scc in the treated group with an injection dose of 0.5 ml/kg BW was more intense, compared to the treated group with an injection dose of 0.2 ml/kg BW. The results of the current study showed that the injection of mesenchymal stem cells-conditioned medium can improve the regeneration of spermatogenic cells, and recover spermatogenesis proved by positive cells of HSD3B1, HSD17B1, and p450scc as markers of steroid production.

scholarly journals Allogeneic human umbilical cord–derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: Study protocol for a randomized controlled trial (MSC-BPD Trial)

2019 ◽  
Author(s):  
Xian Wu ◽  
Yunqiu Xia ◽  
Ou Zhou ◽  
Yan Song ◽  
Xianhong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Randomized Controlled Trial ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Controlled Trial ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Safety And Efficacy ◽  
Randomized Controlled

Abstract Background: Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases with a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in other diseases. We hypothesized that intravenous allogeneic hUC-MSCs are safe and effective for severe BPD. Methods: The MSC-BPD trial is a randomized single-center open-label dose-escalation phase II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 72 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will receive a low dose of hUC-MSCs (n = 24; 2.5 million cells/kg) or a high dose of hUC-MSCs (n = 24; 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n = 24) will be treated with traditional supportive treatments alone without hUC-MSCs. The primary outcome measures will be cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, and 24 months post-intervention, and the key outcome during follow-up will be changes on chest radiography. Statistical analyses will evaluate the efficacy of the hUC-MSC treatment. Discussion: This will be the first randomized controlled trial to evaluate the safety and efficacy of intravenous hUC-MSCs in children with severe BPD. Its results will provide a new evidence-based therapy for severe BPD.

scholarly journals Effect of Adipose-Derived Mesenchymal Stem Cell on the Expressions of Bax/Bcl-2, Ki67, VEGF, TNF-α, and Endometrial Implants in Metformin-Administered Endometriosis Mice (A Mouse Model in Endometriosis Study)

2021 ◽  
Author(s):  
Inu Mulyantoro ◽  
Noor Pramono Noerpramana ◽  
Yuda Heru Febrianto ◽  
Widjiati Widjiati ◽  
Purwati Purwati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immunohistochemical Staining ◽  
Control Group ◽  
Effective Management ◽  
Tnf Α ◽  
Significant Difference ◽  
The World ◽  
Post Hoc ◽  
Tracing Method

Objective: Endometriosis is a gynecological syndrome that affects many women around the world. The effective management for this illness has not been determined. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) and metformin on Bax/Bcl-2, Ki67, VEGF, TNF-α, and endometrial implants in endometriosis mice. Materials and Methods: Thirty mice with endometriosis were equally divided into 5 experimental groups (S1: 0.1 ml MSCs + 4 mg metformin; S2: 0.1 ml MSCs; S3: 4 mg metformin; S4: 0.1 ml NaCl 9%; and S5: 4 mg metformin + subsequent 0.1 ml MSCs) for 14 days. On the 15th day, peritoneal tissues of mice and endometrial implants were removed to examine the expressions of Bax/Bcl-2, Ki67, VEGF, and TNF-α using immunohistochemical staining, and Allred index and endometrial implants using image tracing method with a computer. The obtained data were analyzed using the Kruskal-Wallis and ANOVA tests, followed by the Least Significant Difference (LSD) and Mann-Whitney Post-hoc tests. Results: There were significant differences in the expressions of Bax/Bcl-2 (p=0.002), Ki67 (p=0.004), TNF-α (p=0.017), and endometrial implants (p=0.001) in all groups, except for VEGF (p=0.079). The values of S2 didn’t differ much compared to the control group (S4) in the Bax/Bcl-2 (p=0.487), TNF-α (p=0.191), and endometrial implants (p=0.2). S1 was found to have the highest Bax/Bcl-2 (1.67±0.845) and lowest TNF-α (4.67±2.15) and endometrial implant (0.86±2.11). Conclusion: MSCs alone had not any beneficial effect on the treatment of endometriosis, whereas metformin by itself exhibited favorable results. The combination of MSCs and metformin at the same time shows superior outcomes.

scholarly journals Neuroprotective Effects of Microfluidic Encapsulated Induced Conjunctival Mesenchymal Stem Cells Through Autophagy Modulation in a Parkinsonian Model

2021 ◽  
Author(s):  
Hossein Mostafavi ◽  
Meysam Forouzandeh ◽  
Mohammad Reza Bigdeli ◽  
Samad Nadri ◽  
Mehdi Eskandari
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Control Group ◽  
Mrna Levels ◽  
Significant Difference ◽  
Free Cells

Abstract Background and Aim: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreases rated of autophagy. According to recent studies, cell therapy has been attracted much attention for PD treatment. Due to the many advantages mesenchymal stem cells (MSCs) have proposed, they have been considered a valuable resource for PD cell therapy. The present study aimed to investigate the therapeutic effect of Conjunctival MSCs (CJ-MSCs) on the autophagy manner and the expression of Mammalian target of rapamycin (mTOR), TH, and α-Syn in the parkinsonian rat model.Materials and Methods: our investigation has been performed using the Parkinson's model of rats. Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs both encapsulated and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses have been carried out to evaluate the potency of CJ-MSCs (both encapsulated and free cells) on PD rats. The Rotation, Rotarod Open field test was recruited as the behavioral tests. Immunohistochemistry was used to determine the tyrosine hydroxylase (TH), and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) has been performed for investigating the α-Syn and mTOR gene expression.Results: Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. Immunohistochemistry analysis revealed an increase in the number of TH+ cells compared to the control group. The gene expression evaluation showed a significant reduction in mTOR and α-Syn mRNA levels than the control group. Our results also represented a significant difference between rats receiving encapsulated CJ-MSCs compared to the group received free CJ-MSCs.Conclusion: It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by reducing mTOR and thus increase TH expression that led improve the motor functions of rats. Our results indicated the CJ-MSCs as a suitable source of MSCs to reduce PD complications.

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