Stem Cell Therapy In Patients Research Articles

Efficacy and Safety of Bone Marrow Derived Stem Cell Therapy for Ischemic Stroke: Evidence from Network Meta-analysis.

Several types of stem cells are available for the treatment of stroke patients. However, the optimal type of stem cell remains unclear. To analyze the effects of bone marrow-derived stem cell therapy in patients with ischemic stroke by integrating all available direct and indirect evidence in network meta-analyses. We searched several databases to identify randomized clinical trials comparing clinical outcomes of bone marrow-derived stem cell therapy vs. conventional treatment in stroke patients. Pooled relative risks (RRs) and mean differences (MDs) were reported. The surface under the cumulative ranking (SUCRA) was used to rank the probabilities of each agent regarding different outcomes. Overall, 11 trials with 576 patients were eligible for analysis. Three different therapies, including mesenchymal stem cells (MSCs), mononuclear stem cells (MNCs), and multipotent adult progenitor cells (MAPCs), were assessed. The direct analysis demonstrated that stem cell therapy was associated with significantly reduced all-cause mortality rates (RR 0.55, 95% CI 0.33 to 0.93; I2=0%). Network analysis demonstrated MSCs ranked first in reducing mortality (RR 0.42, 95% CrI 0.15 to 0.86) and improving modified Rankin Scale score (MD -0.59 95% CI -1.09 to -0.09), with SUCRA values 80%, and 98%, respectively. Subgroup analysis showed intravenous transplantation was superior to conventional therapy in reducing all-cause mortality (RR 0.53, 95% CrI 0.29 to 0.88). Using stem cell transplantation was associated with reduced risk of death and improved functional outcomes in patients with ischemic stroke. Additional large trials are warranted to provide more conclusive evidence.

Safety and Feasibility of Mesenchymal Stem Cell Therapy in Patients with Critical COVID-19 Infection – A Comparative Study

Safety and Feasibility of Mesenchymal Stem Cell Therapy in Patients with Critical COVID-19 Infection – A Comparative Study

Comparative effectiveness of mesenchymal stem cell versus bone-marrow mononuclear cell transplantation in heart failure: a meta-analysis of randomized controlled trials

BackgroundThere is no clear evidence on the comparative effectiveness of bone-marrow mononuclear cell (BMMNC) vs. mesenchymal stromal cell (MSC) stem cell therapy in patients with chronic heart failure (HF).MethodsUsing a systematic approach, eligible randomized controlled trials (RCTs) of stem cell therapy (BMMNCs or MSCs) in patients with HF were retrieved to perform a meta-analysis on clinical outcomes (major adverse cardiovascular events (MACE), hospitalization for HF, and mortality) and echocardiographic indices (including left ventricular ejection fraction (LVEF)) were performed using the random-effects model. A risk ratio (RR) or mean difference (MD) with corresponding 95% confidence interval (CI) were pooled based on the type of the outcome and subgroup analysis was performed to evaluate the potential differences between the types of cells.ResultsThe analysis included a total of 36 RCTs (1549 HF patients receiving stem cells and 1252 patients in the control group). Transplantation of both types of cells in patients with HF resulted in a significant improvement in LVEF (BMMNCs: MD (95% CI) = 3.05 (1.11; 4.99) and MSCs: MD (95% CI) = 2.82 (1.19; 4.45), between-subgroup p = 0.86). Stem cell therapy did not lead to a significant change in the risk of MACE (MD (95% CI) = 0.83 (0.67; 1.06), BMMNCs: RR (95% CI) = 0.59 (0.31; 1.13) and MSCs: RR (95% CI) = 0.91 (0.70; 1.19), between-subgroup p = 0.12). There was a marginally decreased risk of all-cause death (MD (95% CI) = 0.82 (0.68; 0.99)) and rehospitalization (MD (95% CI) = 0.77 (0.61; 0.98)) with no difference among the cell types (p > 0.05).ConclusionBoth types of stem cells are effective in improving LVEF in patients with heart failure without any noticeable difference between the cells. Transplantation of the stem cells could not decrease the risk of major adverse cardiovascular events compared with controls. Future trials should primarily focus on the impact of stem cell transplantation on clinical outcomes of HF patients to verify or refute the findings of this study.

Efficacy of stem cell therapy in patients with chronic liver disease: an umbrella review of systematic reviews.

Stem cell therapy offers promising benefits like modulating immune responses, reducing inflammation, and aiding liver regeneration. This umbrella review seeks to compile evidence from systematic reviews to assess the efficacy of stem cell therapy for improving liver function and survival rates in chronic liver disease patients. We searched electronic databases up to February 15, 2024. The selection process focused on systematic reviews comparing stem cell therapy with standard care or a placebo. The primary outcomes evaluated were changes in liver enzymes, the MELD score, and survival rates. Nested Knowledge software was utilized for screening and data extraction. All statistical analyses were performed using R software, version 4.3. Our umbrella review included 28 systematic reviews. The meta-analysis showcased a notable improvement in survival rates with a pooled RR of 1.487 (95% CI: 1.281 to 1.727). In non-randomized studies, albumin levels exhibited an SMD of 0.786 (95% CI: 0.368 to 1.204), indicating positive therapeutic effects. For ALT, the meta-analysis revealed a decrease in levels with an SMD of -0.499 (95% CI: -0.834 to -0.164), and for AST, an overall SMD of -0.362 (95% CI: -0.659 to -0.066) was observed, suggesting hepatoprotective effects. No significant changes were observed in total bilirubin levels and MELD scores in RCTs. Stem cell therapy exhibits potential as a novel treatment for chronic liver diseases, as it has demonstrated improvements in survival rates and certain liver function markers. More high-quality RCTs are needed in the future to fully ascertain the efficacy of stem cell therapy in this patient population.

An update on stem cell therapy for stroke patients: Where are we now?

With a foundation built upon initial work from the 1980s demonstrating graft viability in cerebral ischemia, stem cell transplantation has shown immense promise in promoting survival, enhancing neuroprotection and inducing neuroregeneration, while mitigating both histological and behavioral deficits that frequently accompany ischemic stroke. These findings have led to a number of clinical trials that have thoroughly supported a strong safety profile for stem cell therapy in patients but have generated variable efficacy. As preclinical evidence continues to expand through the investigation of new cell lines and optimization of stem cell delivery, it remains critical for translational models to adhere to the protocols established through basic scientific research. With the recent shift in approach towards utilization of stem cells as a conjunctive therapy alongside standard thrombolytic treatments, key issues including timing, route of administration, and stem cell type must each be appropriately translated from the laboratory in order to resolve the question of stem cell efficacy for cerebral ischemia that ultimately will enhance therapeutics for stroke patients towards improving quality of life.

Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: An umbrella review of systematic reviews.

Stem cell therapy (SCT) has emerged as a potential therapeutic avenue, with various cell types being explored for their efficacy in treating DCM. However, the safety and efficacy of these therapies have been the subject of numerous systematic reviews. This umbrella review aims to consolidate the existing evidence on stem cell interventions for DCM, providing a comprehensive overview of the current research landscape. This review was conducted following the JBI and PRISMA guidelines. Systematic reviews and meta-analyses of randomized controlled trials (RCTs) evaluating the safety and efficacy of SCT for DCM were included. Outcomes such as 6MWT, LVEDD, LVEF, MACE, NYHA, and QoL, among others, were considered. A literature search was executed across databases like PubMed, Embase, Web of Science, and Cochrane Database up to October 07, 2023. The quality of the included reviews was assessed using the JBI Checklist for Systematic Reviews and Research Syntheses. Data synthesis was carried out in both narrative and tabular formats, with the GRADE criteria guiding the determination of evidence certainty. Nine systematic reviews met the inclusion criteria. LVEF found to be significantly improved with SCT. LVEDD and LVEDV assessments yielded mixed results, with some reviews observing significant changes. LVESV showed consistent reductions across multiple studies. BNP concentrations post-interventions were explored in several studies, with mixed findings. Health-related quality of life (HRQL) showed varied results, with some studies noting improvements and others finding no significant differences. NYHA classifications and 6-MWT results indicated potential benefits from stem cell treatments. SCT was observed to be generally safe. The certainty of evidence was low or very low for most of outcomes. SCT showed has shown promise in treating DCM, with many studies highlighting its safety and potential benefits. Nonetheless, the existing data has its limitations due to biases in the RCTs studies. To truly establish the benefits of SCT for DCM, future high quality RCTS, are crucial.

Identifying optimal candidates for autologous peripheral blood stem cell therapy in patients with decompensated liver cirrhosis: a prognostic scoring system.

Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients. From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models. Age, creatinine, neutrophil-to-lymphocyte ratio, and Child-Turcotte-Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633-0.738) and better clinical utility compared with other conventional prognostic models. The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals.

Preliminary outcomes of stem cell therapy in patients with non-obstructive azoospermia

Preliminary outcomes of stem cell therapy in patients with non-obstructive azoospermia

Adipose-derived, autologous mesenchymal stem cell therapy for patients with post-COVID-19 syndrome: an intermediate-size expanded access program

BackgroundEvolving mutations of the novel coronavirus continue to fuel up the pandemic. The virus affects the human respiratory system along with other body systems, causing several sequelae in the survivors of the disease, presented as post-COVID-19 syndrome or long-COVID-19. This protocol utilized Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to evaluate safety and efficacy of HB-adMSC therapy to improve signs and symptoms associated with post-COVID-19 syndrome.MethodsTen eligible subjects with post-COVID-19 syndrome were enrolled in the program for a duration of 40 weeks who received 5 intravenous infusions of 2 × 108 autologous HB-adMSCs each at week 0, 2, 6, 10 and 14 with a follow-up at week 18 and end of the study at week 40. Safety assessments included incidence of adverse and serious adverse events along with the laboratory measures of hematologic, hepatic, and renal function. Efficacy was examined by quality-of-life assessments, fatigue assessments, Visual analog scale (VAS) of symptoms and monitoring of respiration and oxygen saturation rates.ResultsVAS scores and Fatigue Assessment scores (FAS) showed significant improvements post-treatment (P = 0.0039, ES = 0.91) compared to baseline. Respiration rates and oxygen saturation levels that were within the normal range at the baseline remained unchanged at the end of the study (EOS). Paired comparison between baseline and EOS for short-form-36 health survey questionnaire (SF-36) scores also showed improved quality-of-life with significant improvements in individual SF-36 evaluations. Mostly mild AEs were reported during the study period with no incidence of serious AEs. Also, no detrimental effects in laboratory values were seen.ConclusionsThe results of the expanded access program indicated that treatment with autologous HB-adMSCs resulted in significant improvements in the signs and symptoms associated with post-COVID-19 syndrome as assessed by VAS and FAS scores. Additionally, improvements in the patients’ quality-of-life as demonstrated using SF-36 scores that also showed significant improvements in individual scaled scores. Overall, administration of multiple infusions of autologous HB-adMSCs is safe and efficacious for improvements in the quality-of life of patients with post-COVID-19 syndrome.Trial registration: Clinical trial registration number: NCT04798066. Registered on March 15, 2021. (https://clinicaltrials.gov/ct2/show/NCT04798066?term=hope+biosciences&cond=Post-COVID-19+Syndrome&draw=2&rank=2).

Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with critical limb ischemia (CLI)

BackgroundCritical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI.MethodsThis phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 106 and 60 × 106 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes.ResultsAll dosages of P-MSCs, including the highest tested dose of 60 × 106 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly.ConclusionThe observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI.Trial registration: IRCT, IRCT20210221050446N1. Registered May 09, 2021.

Contemporary Challenges of Regenerative Therapy in Patients with Ischemic and Non-Ischemic Heart Failure.

It has now been almost 20 years since first clinical trials of stem cell therapy for heart repair were initiated. While initial preclinical data were promising and suggested that stem cells may be able to directly restore a diseased myocardium, this was never unequivocally confirmed in the clinical setting. Clinical trials of cell therapy did show the process to be feasible and safe. However, the clinical benefits of this treatment modality in patients with ischemic and non-ischemic heart failure have not been consistently confirmed. What is more, in the rapidly developing field of stem cell therapy in patients with heart failure, relevant questions regarding clinical trials' protocol streamlining, optimal patient selection, stem cell type and dose, and the mode of cell delivery remain largely unanswered. Recently, novel approaches to myocardial regeneration, including the use of pluripotent and allogeneic stem cells and cell-free therapeutic approaches, have been proposed. Thus, in this review, we aim to outline current knowledge and highlight contemporary challenges and dilemmas in clinical aspects of stem cell and regenerative therapy in patients with chronic ischemic and non-ischemic heart failure.

Mesenchymal stem cell therapy in patients with Crohn’s disease — 5 year follow-up

Abstract We investigated the efficacy of combination therapy using bone marrow-derived mesenchymal stromal cells (MSC) and Infliximab (IFX) to achieve “deep remission” in patients with luminal Crohn disease (CD). Our study included 72 patients (age 19–62 years) (Ме = 29) with luminal CD. Patients in the 1st group (n = 21) received standard 5-aminosalicylic acid (5-ASA) and glucocorticosteroid therapy in combination with MSC. Patients in the 2nd group (n = 32) were prescribed anti-cytokine therapy IFX. Patients in the 3rd group (n = 19) received MSC and IFX. Clinical and immunobiological (C-reactive protein-CRP and faecal calprotectin-FCP) showed a more significant decrease of local and systemic inflammation activity in the 3rd group of patients. During a 5-year follow-up we observed longer duration of remission in patients who received MSC and IFX compared to the 1st (р = 0,04) and 2nd groups of patients (р = 0.038). Combination therapy of bone marrow-derived MSC and IFL provides “deep remission” in patients with luminal CD and has higher prognostic value for duration of CD remission period.

Efficacy and Safety of Mesenchymal Stem Cell Therapy in Patients with Acute Myocardial Infarction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

The adjuvant treatment of stem cell therapy for acute myocardial infarction (AMI) has been studied in multiple clinical trials, but many questions remain to be addressed, such as efficacy, safety, identification of the optimal cell type, tractable route of delivery, transplant dosage, and transplant timing. The current meta-analysis aimed to explore the issues of mesenchymal stem cells (MSCs) transplantation in patients with AMI based on published randomized controlled trials (RCTs) and guide the design of subsequent clinical trials of MSCs therapy for AMI. The Cochrane Library, PubMed, EMBASE databases were searched for relevant clinical trials from January 1, 2000, to January 23, 2021. Results from RCTs involving MSCs transplantation for the treatment of AMI were identified. According to the Cochrane systematic review method, the literature quality, including studies, was evaluated and valid data was extracted. Rev- Man 5.3 and Stata 15.1 software were used for Meta-analysis. After literature search and detailed evaluation, 9 randomized controlled trials enrolling 460 patients were included in the quantitative analysis. Pooled analyses indicated that MSCs therapy was associated with a significantly greater improvement in overall left ventricular ejection fraction (LVEF), and the effect was maintained for up to 24 months. No significant difference in favor of MSCs treatment in left ventricular (LV) volume and in the risk of rehospitalization as a result of heart failure (HF) was noted, compared with the controls. For transplantation dose, the LVEF of patients accepting a MSCs dose of 107-108 cells was significantly increased by 2.62% (95% CI 1.54 to 3.70; P < 0.00001; I2 =0%), but this increase was insignificant in the subgroup that accepted a MSCs dose of < 107 cells (1.65% in LVEF, 95% CI, 0.03 to 3.27; P =0.05; I2 =75%) or >108 cells (4.65% in LVEF, 95% CI, -4.55 to 13.48; P =0.32; I2 =95%), compared with the controls. For transplantation timing, a significant improvement of LVEF of 3.18% was achieved in the group of patients accepting a MSCs infusion within 2 to 14 days after percutaneous coronary intervention (PCI) (95% CI, 2.89 to 3.47; P <0.00001; I2 = 0). There was no association between MSCs therapy and major adverse events. Results from our systematic review suggest that MSCs therapy for patients with AMI appears to be safe and might induce a significant increase in LVEF with a limited impact on LV volume and rehospitalization caused by HF. The effect was maintained for up to 24 months. MSCs dose of 107-108 cells was more likely to achieve better clinical endpoints than <107 or >108 cells. The optimal time window for cell transplantation might be within 2-14 days after PCI. This meta-analysis was registered with PROSPERO, number CRD 42021241104.

Clinical efficacy analysis of mesenchymal stem cell therapy in patients with COVID-19: A systematic review.

BACKGROUNDCurrently, ongoing trials of mesenchymal stem cells (MSC) therapies for coronavirus disease 2019 (COVID-19) have been reported.AIMIn this study, we investigated whether MSCs have therapeutic efficacy in novel COVID-19 patients.METHODSSearch terms included stem cell, MSC, umbilical cord blood, novel coronavirus, severe acute respiratory syndrome coronavirus-2 and COVID-19, applied to PubMed, the Cochrane Controlled Trials Register, EMBASE and Web of Science.RESULTSA total of 13 eligible clinical trials met our inclusion criteria with a total of 548 patients. The analysis showed no significant decrease in C-reactive protein (CRP) levels after stem cell therapy (P = 0.11). A reduction of D-dimer levels was also not observed in patients after stem cell administration (P = 0.82). Furthermore, interleukin 6 (IL-6) demonstrated no decrease after stem cell therapy (P = 0.45). Finally, we investigated the overall survival (OS) rate after stem cell therapy in COVID-19 patients. There was a significant improvement in OS after stem cell therapy; the OS of enrolled patients who received stem cell therapy was 90.3%, whereas that of the control group was 79.8% (P = 0.02). CONCLUSIONOverall, our analysis suggests that while MSC therapy for COVID-19 patients does not significantly decrease inflammatory markers such as CRP, D-dimer and IL-6, OS is improved.

Multimodality Molecular Imaging of Stem Cells Therapy of Myocardial Infarction

Stem cell therapy in patients with acute myocardial infarction promises a new exciting option. However, the long term fate of stem cells transplanted into myocardial is not clear. Molecular imaging play a vital role in tracking stem cells after intramyocardial delivery as well as in helping us understand the mechanisms of stem cell biology in vivo. In this review, we summarize the principles underlying four kinds of stem cells applied into myocardial infarction and the major tracking methods. Finally, we discuss that molecular imaging will be useful to the successful clinical implementation of this novel therapy.

Amniotic Membrane Enhances the Characteristics and Function of Stem Cell-Derived Retinal Pigment Epithelium Sheets by Inhibiting the Epithelial–Mesenchymal Transition

Human pluripotent stem cell-derived retinal pigment epithelium (iRPE) is an attractive cell source for disease modeling and cell replacement therapy of retinal disorders with RPE defects. However, there are still challenges to develop appropriate culture conditions close to in vivo microenvironment to generate iRPE sheets, which mimic more faithfully the characteristics and functions of the human RPE cells. Here, we developed a simple, novel platform to construct authentic iRPE sheets using human amniotic membrane (hAM) as a natural scaffold. The decellularized hAM (dAM) provided a Bruch's membrane (BM)-like bioscaffold, supported the iRPE growth and enhanced the epithelial features, polarity distribution and functional features of iRPE cells. Importantly, RNA-seq analysis was performed to compare the transcriptomes of iRPE cells cultured on different substrates, which revealed the potential mechanism that dAM supported and promoted iRPE growth was the inhibition of epithelial-mesenchymal transition (EMT). The tissue-engineered iRPE sheets survived and kept monolayer when transplanted into the subretinal space of rabbits. All together, our results indicate that the dAM imitating the natural BM allows for engineering authentic human RPE sheets, which will provide valuable biomaterials for disease modeling, drug screening and cell replacement therapy of retinal degenerative diseases. Statement of significanceEngineered RPE sheets have a great advantage over RPE cell suspension for transplantation as they support RPE growth in an intact monolayer which RPE functions are dependent on. The substrates for RPE culture play a critical role to maintain the physiological functions of the RPE in stem cell therapies for patients with retinal degeneration. In this study, we constructed engineered iRPE sheets on the decellularized human amniotic membrane scaffolds, which contributed to enhancing epithelial features, polarity distribution and functional features of iRPE. dAM exhibited the ability of anti-epithelial mesenchymal transition to support iRPE growth. Furthermore, the results of transplantation in vivo demonstrated the feasibility of iRPE sheets in retina regenerative therapy. Engineering RPE sheets on dAM is a promising strategy to facilitate the development of iRPE replacement therapy and retinal disease modeling.

The differentiation of mesenchymal bone marrow stem cells into nerve cells induced by Chromolaena odorata extracts.

Background: Mesenchymal stem cells (MSCs) can differentiate into nerve cells with an induction from chemical compounds in medium culture. Chromolaena odorata contains active compounds, such as alkaloids and flavonoids, that can initiate the transformation of MSCs into nerve cells. The aim of this study was to determine the potential of methanol extracted C. odorata leaf to induce the differentiation of bone marrow MSCs into nerve cells. Methods: A serial concentration of C. odorata leaf extract (0.7-1.0 mg/mL) with two replications was used. The parameters measured were the number of differentiated MSCs into nerve cells (statistically analyzed using ANOVA) and cell confirmation using reverse transcription polymerase chain reaction (RT-PCR). Results: The results showed that the C. odorata extract had a significant effect on the number MSCs differentiating into nerve cells ( p < 0.05) on the doses of 0.8 mg/ml with 22.6%. Molecular assay with RT-PCR confirmed the presence of the nerve cell gene in all of the samples. Conclusions: In conclusion, this study showed the potential application of C. odorata leaf extract in stem cell therapy for patients experiencing neurodegeneration by inducing the differentiation of MSCs into nerve cells.

A bibliometric analysis of primary ovarian insufficiency from 2010 to 2020

Objective This study aimed to carry out a bibliometric analysis of primary ovarian insufficiency (POI) from 2010 to 2020 and to reveal the research status and hotspots in the future. Method A total of 3087 articles and reviews related to POI published from 2010 to 2020 retrieved from the Web of Science Core Collection were used for bibliometric analysis. CiteSpace and VOSviewer were adopted to analyze countries and regions, organizations, authors, journals, keywords and co-cited references. Results The number of publications about POI increased year by year. The USA produced the largest number of publications and the most influence in this field. The main research directions of POI can be roughly divided into four aspects according to the analysis of keywords and co-cited references: genetic research of POI; stem cell therapy for patients with POI; prediction of ovarian function; and fertility preservation of cancer patients. Genetic research and stem cell therapy may become research hotspots in the future. Conclusion This study might be the first bibliometric study to analyze publications of POI from multiple indicators, in order to provide new opinions for the research trends and possible hotspots of POI.

A meta-analysis of randomized controlled trials on therapeutic efficacy and safety of autologous cell therapy for atherosclerosis obliterans

Objective Atherosclerosis obliterans (ASO) is a chronic occlusive arterial disease and the most common type of peripheral arterial disease. Current treatment options like medication and vascularization have limited effects for “no-option” patients, and stem cell therapy is considered a viable option, although its application and efficacy have not been standardized. The objective of this review was to assess the safety and efficacy of autologous stem cell therapy in patients with ASO.

Mesenchymal Stem Cell Therapy for Patients with Post COVID ARDS on ECMO Referred for Lung Transplantation - Single Center Experience from India

PurposeIndia experienced a devastating second wave of the covid 19 pandemic triggered by the delta variant, which peaked in end of April and early May 2021 with average daily new cases hitting 300,000 to 400,000 and daily death toll reaching 3000 to 3500. ECMO emerged as an option for severe post covid ARDS and was offered in many centers across India for patients who were worsening despite full ventilatory support and prone positioning. A small minority of these patients who showed no improvement despite several weeks on ECMO were referred for lung transplantation to our center. Out of the 63 ECMO pts we received for Lung Transplantation 5 patients received Mesenchymal Stem Cell (MSC) infusion over and above standard treatment after getting necessary clearance from hospital Ethics committee and consent from patients’ familyMethodsWe conducted a case control study on critically ill post covid ARDS patients on ECMO referred for lung transplantation to our center. 5 patients received 2 million umbilical cord derived MSCs/kgwt infused over 30 minutes, for 3 doses on days 0, 3 and 6 and was compared to other local ECMO patients (control group; n=58). The primary outcome was safety and secondary outcome was all cause mortality.ResultsAll 5 patients tolerated MSC infusions well with no side effects observed. Out of the 5 patients who received MSC infusions 3 pts (60%) recovered and were weaned off ECMO successfully. 1 pt (20%) did not improve and expired, 1 pt (20%) did not recover and underwent successful lung transplantation and was discharged home. In the ECMO control group, 15 patients (26%) recovered without transplant, 23 pts (40%) underwent successful lung transplantation and 20 pts (34%) expired.ConclusionMSC IV infusion is safe and well tolerated without side effects in covid ARDS pts on ECMO. The efficacy of MSC in repairing the covid destroyed lung should be further evaluated in large randomised controlled studies.