Efficacy Of Stem Cell Therapy Research Articles

Advances in stem cell therapy in Alzheimer's disease: a comprehensive clinical trial review.

Alzheimer's disease (AD) is the most common type of dementia responsible for more than 121,499 deaths from AD in 2019 making AD the sixth-leading cause in the United States. AD is a progressive neurodegenerative disorder characterized by decline of memory, behavioral impairments that affects a person's ability to function independently ultimately leading to death. The current pressing need for a treatment for (AD) and advances in the field of cell therapy, has rendered stem cell therapeutics a promising field of research. Despite advancements in stem cell technology, confirmed by encouraging pre-clinical utilization of stem cells in AD animal models, the number of clinical trials evaluating the efficacy of stem cell therapy is limited, with the results of many ongoing clinical trials on cell therapy for AD still pending. Mesenchymal stem cells (MSCs) have been the main focus in these studies, reporting encouraging results concerning safety profile, however their efficacy remains unproven. In the current article we review the latest advances regarding different sources of stem cell therapy and present a comprehensive list of every available clinical trial in national and international registries. Finally, we discuss drawbacks arising from AD pathology and technical limitations that hinder the transition of stem cell technology from bench to bedside. Our findings emphasize the need to increase clinical trials towards uncovering the mode of action and the underlying therapeutic mechanisms of transplanted cells as well as the molecular mechanisms controlling regeneration and neuronal microenvironment.

Potential Applications of Low-intensity Extracorporeal Shock-Wave Therapy in Urological Diseases via Activation of Tissue Resident Stem Cells

For many years, low-intensity extracorporeal shock-wave therapy (Li-ESWT) has been clinically applied as a noninvasive therapeutic method, for urological diseases. The major corresponding biological molecular mechanisms of Li-ESWT are to induce stem cell differentiation, neural regeneration, and angiogenesis. This narrative review aims to present an overview of the potential utility of Li-ESWT and its effects on stem cell therapies. Recent studies have also shown that the combination treatment of Li-ESWT and stem cell therapies can be a new option for the treatment of erectile dysfunction (ED), urinary incontinence, bladder dysfunction, and other diseases. The potential contributions of Li-ESWT on stem cell therapies for these diseases are studied, highlighting the influence of Li-ESWT on proliferation, viability, and differentiation capacity of certain stem cells. The potential mechanisms, including the increased expression of vascular endothelial growth factor, chemokine CXC motif ligand 5, and transforming growth factor-β1 are described herein. Li-ESWT can also activate many cellular signaling pathways. The combination of Li-ESWT and stem cell therapies is a promising strategy for urological diseases. However, a much greater understanding of the mechanisms by which Li-ESWT enhances the efficacy of stem cell therapy is still needed before this combined treatment can be recommended for large-scale clinical application.

The Safety and Efficacy of Stem Cell Therapy as an Emerging Therapy for ALS: A Systematic Review of Controlled Clinical Trials

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a heterogeneous course that ultimately leads to death. Currently, there is no cure, and new treatments that can slow the progression of the disease are needed. Stem cell (SC) transplantation is an emerging therapy that has shown a lot of potential in recent clinical trials. This review is aimed to examine the results of various clinical trials on this topic, thus assessing the safety and efficacy of SC transplantation as a potential treatment for ALS. We identified 748 studies in our search, of which 134 full-text studies were assessed for eligibility. Six studies met the inclusion criteria and were included in this review. Although some of the included studies showed the positive effect of SC transplantation, other studies found that there was no significant difference compared to the control group. We observed more positive effects with bone marrow mesenchymal stem cells (BM-MSC) treatments than Granulocyte colony-stimulating factor (G-CSF) ones. However, other factors, such as route of administration, number of doses, and number of cells per dose, could also play a role in this discrepancy. Based on this information, we conclude that more properly conducted clinical trials are needed to appreciate the benefit of this treatment.

Abstract 14138: Effect of Nicotine Exposure to Induced Pluripotent Stem Cell Derived Endothelial Cell Therapy in a Murine Model of Peripheral Artery Disease

Introduction: Clinical solutions for peripheral artery disease (PAD) remain elusive due to the many challenges of surgical intervention. Stem cell therapy offer a promising option, but barriers exist to their clinical translatability. Among these include lifestyle choices like tobacco use that may influence the efficacy of stem cell therapy. The objective of this study aims to examine the potential effects of nicotine on human induced pluripotent stem cell derived endothelial cells (iPSC-ECs) therapy in the context of PAD. Hypothesis: Chronic nicotine exposure negatively affects the therapeutic potential of implanted iPSC-ECs in a murine model of PAD. Methods: Mice were implanted with an osmotic pump for controlled exposed to nicotine or saline (control) for 28 days. Plasma cotinine was measured to confirm nicotine exposure. After 28 days of nicotine or saline exposure, the mice underwent induction of hindlimb ischemia and before receiving an injection of 10 6 iPSC-ECs. A second dose of cells were injected to the ischemic limb on day 7 post-surgery. All mice were monitored for blood perfusion recovery using laser Doppler spectroscopy imaging. Survival of the transplanted cells in vivo were tracked by bioluminescence imaging. The mice receiving iPSC-ECs were also imaged for cell survival using bioluminescence imaging. At day 14 post-surgery, mice were euthanized, and the gastrocnemius muscle and thigh muscle were harvested for histological analysis. Results: The average cotinine concentration in sera was ~200 ng/mL, which is within physiological range for a tobacco user. Blood perfusion recovery at day 14 showed trends of nicotine treated groups have hindered perfusion recovery, compared to those treated with saline. Importantly, nicotine exposure trended with poorer perfusion recovery after cell therapy. Bioluminescent imaging showed iPSC-ECs persisted in vivo for all groups without significant difference. Conclusion: Nicotine exposure was associated with poorer blood perfusion recovery after iPSC-EC therapy, compared to control saline exposure, suggesting that nicotine may have adverse effects on iPSC-EC therapy for treatment of PAD.

Mesenchymal stem cell therapy efficacy in COVID-19 patients: A systematic review and meta-analysis

Objective: To evaluate mesenchymal stem cell (MSC) administration safety and efficacy in COVID-19 patients. Methods: We conducted a literature search on PubMed/MEDLINE, medRxiv, EBSCOhost/CINAHL, ProQuest, and Scopus with keywords adjusted to each search engine’s specifications on February 12, 2021. Interventional studies that reviewed MSC efficacy (mortality, hospitalization duration, need for mechanical ventilators, and inflammation markers) and/or safety (adverse events) in COVID-19 patients who were 18 years old or more were included in this study. Study eligibility, data extraction, and study quality assessment were conducted independently by each author. Results: A total of five studies of moderate to high quality with a total of 193 patients were included. One of the three randomized studies included did not apply blinding to either participants or medical professionals. Pooled OR (Odd Ratio) for mortality risk, adverse events incidence, and use of mechanical ventilators for patients on MSC therapy were 0.13 [95% CI: 0.02, 0.68], 0.91 [95% CI: 0.45, 1.86], and 0.42 [95% CI: 0.12, 1.47], respectively. Pooled mean difference for hospitalization duration in the MSC group versus the control was -3.54 [CI 95%: -4.68, -2.40] with 7% heterogeneity. All studies agreed that there was an increase of pro-inflammatory cytokines and a decrease of anti-inflammatory markers that were statistically different in the MSC group. Conclusion: Mesenchymal stem cell administration to COVID-19 patients is safe and effective in reducing mortality and hospitalization duration. Furthermore, a decrease of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines were observed.

The presence of sensational language describing stem cell therapies in news articles: a cross-sectional analysis.

Aim: News articles and their use of sensational language have the potential to influence health behaviors and decisions, thus the purpose of this study was to evaluate the use of sensational language (i.e., superlatives) describing stem cell therapies in public news articles. Materials & methods: In this study, we conducted a Google News search for news articles using superlatives to exaggerate the efficacy of stem cell therapies. Results: Our analysis included 262 news articles from 193 news outlets using 714 unique superlatives to describe stem cells. Health on the Net's Code of Conduct certification was applied to determine credibility of each site. Conclusion: These results demonstrate the need for improving news reporting surrounding stem cell research and therapies.

Mesenchymal Stem Cell Applications in Spine Disorders: A Comprehensive Review

Mesenchymal stem cells (MSCs) are increasingly being employed in a number of orthopedic settings, in particular in the treatment of hip and knee osteoarthritis. Recently, the use MSCs has been investigated for different spine settings. However, the use of these cells is not yet widespread in the clinical practice. The aim of this review was to investigate the current literature regarding the use of MSCs in different spine conditions and discuss possible future applications. In particular, degenerative disc disease is the most studied field for MSC application, and is the only one that has already reached the clinical practice, albeit not routinely. Spinal cord injuries are another extensively investigated use of MSCs: despite encouraging preliminary results, a consensus on the efficacy of stem cell therapy for spinal cord injuries has not yet been reached, and their use is still only experimental.

RETRACTED ARTICLE: GDF11 enhances therapeutic functions of mesenchymal stem cells for angiogenesis

BackgroundThe efficacy of stem cell therapy for ischemia repair has been limited by low cell retention rate. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family, which has multiple effects on development, physiology and diseases. The objective of the study is to investigate whether GDF11 could affect the efficacy of stem cell transplantation.MethodsWe explored the effects of GDF11 on proangiogenic activities of mesenchymal stem cells (MSCs) for angiogenic therapy in vitro and in vivo.ResultsMouse bone marrow-derived MSCs were transduced with lentiviral vector to overexpress GDF11 (MSCGDF11). After exposed to hypoxia and serum deprivation for 48 h, MSCGDF11 were significantly better in viability than control MSCs (MSCvector). MSCGDF11 also had higher mobility and better angiogenic paracrine effects. The cytokine antibody array showed more angiogenic cytokines in the conditioned medium of MSCGDF11 than that of MSCvector, such as epidermal growth factor, platelet-derived growth factor-BB, placenta growth factor. When MSCs (1 × 106 cells in 50 μl) were injected into ischemic hindlimb of mice after femoral artery ligation, MSCGDF11 had higher retention rate in the muscle than control MSCs. Injection of MSCGDF11 resulted in better blood reperfusion and limb salvage than that of control MSCs after 14 days. Significantly more CD31+ endothelial cells and α-SMA + smooth muscle cells were detected in the ischemic muscles that received MSCGDF11. The effects of GDF11 were through activating TGF-β receptor and PI3K/Akt signaling pathway.ConclusionOur study demonstrated an essential role of GDF11 in promoting therapeutic functions of MSCs for ischemic diseases by enhancing MSC viability, mobility, and angiogenic paracrine functions.

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis.

Objective Osteoporosis is an abnormal bone metabolism disease characterized by microstructural degeneration of bone tissue and reduction in bone mass, resulting in increased brittleness of bone tissue and susceptibility to fracture. Due to the tissue regenerative potential of stem cell transplantation, it is now used in the treatment of various disease models such as osteoporosis. The purpose of this work is to carry out a systematic review and meta-analysis of the efficacy of stem cell therapy in ovariectomized (OVX) osteoporotic rats. Methods PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang Databases were used to search for articles that met the inclusion criteria. Two researchers independently screened the articles that met the inclusion criteria. RevMan 5.3 and STATA 16.0 were used for data analysis. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202150017. Results Thirteen eligible studies were selected, including 405 rats. The sources of stem cells are divided into four main categories: bone marrow mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), amniotic membrane mesenchymal stem cells (AM-MSCs), and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Compared with the OVX group, both stem cell transplantation groups had higher bone mineral density (BMD) (BMSCs: SMD = 2.01, 95% CI: [1.38, 2.63], P < 0.001, I2 = 76.6%; ADSCs: SMD = 2.24, 95% CI: [0.79, 3.69], P = 0.003, I2 = 86.7%) and bone volume/total volume (BV/TV) (hUCB-MSCs: SMD = 1.71, 95% CI: [0.97, 2.44], P < 0.001, I2 = 0%; ADSCs: SMD = 2.16, 95% CI: [0.27, 4.04], P = 0.025, I2 = 82.6%). In the BMSC treatment groups, the trabecular numbers (Tb.N) (SMD = 4.28, 95% CI: [0.91, 7.64], P = 0.013, I2 = 94.9%) were significantly higher, whereas the results for trabecular thickness (Tb.Th) (SMD = 2.7, 95% CI: [-0.34, 5.73], P = 0.081, I2 = 95.4%) and trabecular spacing (Tb.Sp) (SMD = −3.08, 95% CI: [-6.55, 0.38], P = 0.081, I2 = 96.3%) were not statistically significant compared to those of the OVX group. The stem cell transplantation group had a low BMD, BV/TV, and Tb.N compared to the sham operation group. Conclusion Stem cell therapy may increase bone strength, bone volume, and the number of trabeculae in OVX osteoporotic rats. The results of this meta-analysis showed the potential therapeutic effect of stem cell transplantation in OVX osteoporotic rats, bringing new therapeutic ideas and directions to the clinical treatment of osteoporosis. Due to the limited number and quality of studies related to some outcomes, more high-quality RCTs are still needed in the future to complement the existing findings.

Regulation of Inflammatory Cytokine Storms by Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have been widely used in preclinical and clinical trials for various diseases and have shown great potential in the treatment of sepsis and coronavirus disease (COVID-19). Inflammatory factors play vital roles in the pathogenesis of diseases. The interaction between inflammatory factors is extremely complex. Once the dynamics of inflammatory factors are unbalanced, inflammatory responses and cytokine storm syndrome develop, leading to disease exacerbation and even death. Stem cells have become ideal candidates for the treatment of such diseases due to their immunosuppressive and anti-inflammatory properties. However, the mechanisms by which stem cells affect inflammation and immune regulation are still unclear. This article discusses the therapeutic mechanism and potential value of MSCs in the treatment of sepsis and the novel COVID-19, outlines how MSCs mediate innate and acquired immunity at both the cellular and molecular levels, and described the anti-inflammatory mechanisms and related molecular pathways. Finally, we review the safety and efficacy of stem cell therapy in these two diseases at the preclinical and clinical levels.

A systematic review and meta-analysis on the efficacy of stem cell therapy on bone brittleness in mouse models of osteogenesis imperfecta

There is no cure for osteogenesis imperfecta (OI), and current treatments can only partially correct the bone phenotype. Stem cell therapy holds potential to improve bone quality and quantity in OI. Here, we conduct a systematic review and meta-analysis of published studies to investigate the efficacy of stem cell therapy to rescue bone brittleness in mouse models of OI. Identified studies included bone marrow, mesenchymal stem cells, and human fetal stem cells. Effect size of fracture incidence, maximum load, stiffness, cortical thickness, bone volume fraction, and raw engraftment rates were pooled in a random-effects meta-analysis. Cell type, cell number, injection route, mouse age, irradiation, anatomical bone, and follow up time were considered as moderators. It was not possible to investigate further parameters due to the lack of standards of investigation between the studies. Despite the use of oim mice in the majority of the investigations considered and the lack of sham mice as control, this study demonstrates the promising potential of stem cell therapy to reduce fractures in OI. Although their low engraftment, cell therapy in mouse models of OI had a beneficial effect on maximum load, but not on stiffness, cortical thickness and bone volume. These parameters all depend on bone geometry and do not inform on its material properties. Being bone fractures the primary symptom of OI, there is a critical need to measure the fracture toughness of OI bone treated with stem cells to assess the actual efficacy of the treatment to rescue OI bone brittleness.

Diagnosis and Treatment Guidelines for Mesenchymal Stem Cell Therapy for Coronavirus Disease 2019 (Beijing, 2021)

AbstractThe coronavirus disease 2019 (COVID-19) can be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and has led to millions of deaths among more than 100 million infected people around the world according to the declaration from World Health Organization. Dysregulated immune response of both the innate and adaptive immune systems is subsistent on COVID-19 patients, of which the degree are associated with disease severity, lung damage and long term functional disability. Current treatment options have included antiretroviral drugs, anti-inflammatory factors, antibodies, immune checkpoint inhibitors, and convalescent plasma therapy. More recently, mesenchymal stem cell (MSC) therapy has been explored for the management and control of COVID-19, particularly with the aim of preventing or at least mitigating respiratory co-morbidities. Though the safety and efficacy of stem cell therapy have been validated in multiple phase I–III clinical trials, to date, no standardized stem cell preparation, administration dosage or interval, product QA/QC testing, storage, transportation, or disposal protocols have been established. The present paper proposes a systematic methodology that addresses all the foregoing process steps and evaluation criteria for the efficacious and safe administration of MSCs in the treatment of patients infected with COVID-19.

Hyaluronic Acid Supplement as a Chondrogenic Adjuvant in Promoting the Therapeutic Efficacy of Stem Cell Therapy in Cartilage Healing.

The main aim of this study is to investigate the therapeutic efficacy of direct intra-articular injection of bone-marrow-derived stem/stromal cells (BMSCs) and the adjuvant role of hyaluronic acid (HA) in facilitating rabbit articular cartilage repair. First, rabbit BMSCs were treated with a medium containing different concentrations of HA. Later, HA’s influence on BMSCs’ CD44 expression, cell viability, extracellular glycosaminoglycan (GAG) synthesis, and chondrogenic gene expression was evaluated during seven-day cultivation. For the in vivo experiment, 24 rabbits were used for animal experiments and 6 rabbits were randomly allocated to each group. Briefly, chondral defects were created at the medial femoral condyle; group 1 was left untreated, group 2 was injected with HA, group 3 was transplanted with 3 × 106 BMSCs, and group 4 was transplanted with 3 × 106 BMSCs suspended in HA. Twelve weeks post-treatment, the repair outcome in each group was assessed and compared both macroscopically and microscopically. Results showed that HA treatment can promote cellular CD44 expression. However, the proliferation rate of BMSCs was downregulated when treated with 1 mg/mL (3.26 ± 0.03, p = 0.0002) and 2 mg/mL (2.61 ± 0.04, p = 0.0001) of HA compared to the control group (3.49 ± 0.05). In contrast, 2 mg/mL (2.86 ± 0.3) of HA treatment successfully promoted normalized GAG expression compared to the control group (1.88 ± 0.06) (p = 0.0009). The type II collagen gene expression of cultured BMSCs was significantly higher in BMSCs treated with 2 mg/mL of HA (p = 0.0077). In the in vivo experiment, chondral defects treated with combined BMSC and HA injection demonstrated better healing outcomes than BMSC or HA treatment alone in terms of gross grading and histological scores. In conclusion, this study helps delineate the role of HA as a chondrogenic adjuvant in augmenting the effectiveness of stem-cell-based injection therapy for in vivo cartilage repair. From a translational perspective, the combination of HA and BMSCs is a convenient, ready-to-use, and effective formulation that can improve the therapeutic efficacy of stem-cell-based therapies.

Multipronged Attack of Stem Cell Therapy in Treating the Neurological and Neuropsychiatric Symptoms of Epilepsy.

Epilepsy stands as a life-threatening disease that is characterized by unprovoked seizures. However, an important characteristic of epilepsy that needs to be examined is the neuropsychiatric aspect. Epileptic patients endure aggression, depression, and other psychiatric illnesses. Therapies for epilepsy can be divided into two categories: antiepileptic medications and surgical resection. Antiepileptic drugs are used to attenuate heightened neuronal firing and to lessen seizure frequency. Alternatively, surgery can also be conducted to physically cut out the area of the brain that is assumed to be the root cause for the anomalous firing that triggers seizures. While both treatments serve as viable approaches that aim to regulate seizures and ameliorate the neurological detriments spurred by epilepsy, they do not serve to directly counteract epilepsy’s neuropsychiatric traits. To address this concern, a potential new treatment involves the use of stem cells. Stem cell therapy has been employed in experimental models of neurological maladies, such as Parkinson’s disease, and neuropsychiatric illnesses like depression. Cell-based treatments for epilepsy utilizing stem cells such as neural stem cells (NSCs), mesenchymal stem cells (MSCs), and interneuron grafts have been explored in preclinical and clinical settings, highlighting both the acute and chronic stages of epilepsy. However, it is difficult to create an animal model to capitalize on all the components of epilepsy due to the challenges in delineating the neuropsychiatric aspect. Therefore, further preclinical investigation into the safety and efficacy of stem cell therapy in addressing both the neurological and the neuropsychiatric components of epilepsy is warranted in order to optimize cell dosage, delivery, and timing of cell transplantation.

Safety and efficacy of stem cell therapy: an overview protocol on published meta-analyses and evidence mapping.

BackgroundStem cell therapy (SCT) is an emerging and promising treatment measure for many conditions (e.g., chronic liver disease, diabetes mellitus, and knee osteoarthritis). Although there are numerous meta-analyses (MAs) concerning SCT, the quality of these MAs and the efficacy and safety data for SCT reported in these MAs remain unknown. Therefore, it is of utmost importance to conduct an overview of existing MAs concerning SCT for evaluating these parameters.MethodsWe will systematically search PubMed and EMBASE databases from inception to October 2020 for identifying MAs of SCT published in English. Two independent reviewers will select appropriate MAs against the predefined eligibility criteria. The efficacy and safety data of SCT reported in MAs will be descriptively summarized. Following this, the reporting quality and methodological quality of included MAs will be appraised using Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) tools by two reviewers, respectively. Further, the evidence mapping method will be used to present assessment results. The key information will also be extracted by two independent reviewers. The Spearman’s correlation coefficient will be used to explore the association between reporting quality and methodological quality. The factors influencing the quality will be assessed through linear regression analyses. The sensitivity analysis will also be conducted. Data analyses will be performed using Stata 16.0 and Excel 2016. P<0.05 will be considered statistically significant.DiscussionThis overview of MAs concerning SCTs will provide comprehensive evidence on the quality of MAs and data of interest reported in MAs. Further, these data can be used to guide clinical practice and future research.Overview registrationInternational Prospective Register of Systematic Reviews (PROSPERO): CRD42020206642.

Narrative review of stem cell therapy for ischemic brain injury.

Ischemic brain injury is a common cause of long-term neurological deficits in children as well as adults, and no efficient treatments could reverse the sequelae in clinic till now. Stem cells have the capacity of self-renewal and multilineage differentiation. The therapeutic efficacy of stem cell transplantation for ischemic brain injury have been tested for many years. The grafts could survive and mature in the ischemic brain environment. Stem cell transplantation could improve functional recovery of ischemic brain injury models in pre-clinical trials. The potential mechanisms included cell replacement, release of neurotrophic and anti-inflammatory factors, immunoregulation as well as activation of endogenous neurogenesis. Besides, many clinical trials were conducted and some of trials already had preliminary results. From the current published data, cell transplantation for clinical application is safe and feasible. No severe adverse events and tumorigenesis were reported. While the therapeutic efficacy of stem cell therapy in clinic still needs more evidences. In this review, we overviewed the studies about stem cell therapy for ischemic brain injury. Different types of stem cells used for transplantation as well as the therapeutic mechanisms were discussed in detail. The related pre-clinical and clinical trials were summarized into two separate tables. In addition, we also discussed the unsolved problems and concerns about stem cell therapy for ischemic brain injury that need to be overcome before clinic transformation.

Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have demonstrated potential in treating diabetic cardiomyopathy. However, patients with diabetes are on multiple drugs and there is a lack of understanding of how transplanted stem cells would respond in presence of such drugs. Metformin is an AMP kinase (AMPK) activator, the widest used antidiabetic drug. In this study, we investigated the effect of metformin on the efficacy of stem cell therapy in a diabetic cardiomyopathy animal model using streptozotocin (STZ) in male Wistar rats. To comprehend the effect of metformin on the efficacy of BM-MSCs, we transplanted BM-MSCs (1 million cells/rat) with or without metformin. Our data demonstrate that transplantation of BM-MSCs prevented cardiac fibrosis and promoted angiogenesis in diabetic hearts. However, metformin supplementation downregulated BM-MSC-mediated cardioprotection. Interestingly, both BM-MSCs and metformin treatment individually improved cardiac function with no synergistic effect of metformin supplementation along with BM-MSCs. Investigating the mechanisms of loss of efficacy of BM-MSCs in the presence of metformin, we found that metformin treatment impairs homing of implanted BM-MSCs in the heart and leads to poor survival of transplanted cells. Furthermore, our data demonstrate that metformin-mediated activation of AMPK is responsible for poor homing and survival of BM-MSCs in the diabetic heart. Hence, the current study confirms that a conflict arises between metformin and BM-MSCs for treating diabetic cardiomyopathy. Approximately 10% of the world population is diabetic to which metformin is prescribed very commonly. Hence, future cell replacement therapies in combination with AMPK inhibitors may be more effective for patients with diabetes.NEW & NOTEWORTHY Metformin treatment reduces the efficacy of mesenchymal stem cell therapy for cardiac repair during diabetic cardiomyopathy. Stem cell therapy in diabetics may be more effective in combination with AMPK inhibitors.

Stem Cell Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background and Objective:Stem cell therapy has emerged as a potential therapy for the treatment of stroke. We performed a systematic review and meta-analysis of published randomized controlled studies using various types of stem cell therapies in patients with ischemic stroke (IS).Method:Literature search was carried out using PubMed, Google Scholar, Cochrane library, and clinicaltrial.gov to identify studies on stem cell therapy in IS from its inception till January 2020. Data were extracted independently by two reviewers. STATA version 13 was used for carrying out meta- analysis. We included only randomized controlled trials (RCTs) if any of the stem cell therapy was used to treat patients with IS in any phase after the index stroke.Results:We included a total of eight randomized controlled studies involving 459 subjects (217 intervention and 242 controls) in the meta-analysis. We did not observe statistically significant reduction in mean NIHSS score in the intervention group (SMD - 0.34, 95% CI - 0.76 to 0.08) in patients with acute or sub-acute stroke. However, a statistically significant reduction (SMD - 1.57, 95% CI -2.22 to -0.92) was observed in patients with chronic ischemic stroke. Statistically non-significant reduction in mean mRS in the intervention group (SMD 0.04, 95% CI -0.20 to 0.28) in patients with acute or sub-acute ischemic stroke was observed, however a statistically significant reduction (SMD - 1.07, 95% CI - 1.94 to -0.19) was noted in patients with chronic stroke. We did not observe statistically significant reduction in mean Barthel index score (SMD 0.24, 95%CI -1.69 to 2.17) in chronic stroke. Statistically non-significant lower mortality rate was observed in intervention group compared to controls (Risk Ratio 0.84, 95% CI 0.43 to 1.66) among acute or sub-acute, as well as in the chronic stroke group (Risk Ratio 0.47, 95% CI 0.20 to 1.09).Conclusion:Our meta-analysis provides no clinically important evidence for efficacy of stem cells in reducing neurological deficit compared to control group. Well-designed large randomized controlled trials are required to provide more information on the efficacy of stem cell therapy in patients with IS.

Stem cell therapy targets the neointimal smooth muscle cells in experimentally induced atherosclerosis: involvement of intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM).

Smooth muscle cells (SMCs) are currently considered a central pivotal player in pathogenesis and development of atherosclerotic lesions. As consequence of vascular injury, SMCs migrate from the tunica media into the tunica intima layers where they contribute to neointimal formation by converting into foam cells and producing pro-inflammatory and oxidative stress markers. We targeted the replacement of neointimal SMCs by using the mesenchymal stem cells (MSCs) therapy in experimentally induced atherosclerosis in an attempt to improve the atherosclerotic lesion and its concomitant complications. Rats were divided into 4 groups (n=20). Control group: rats kept on a standard chow diet; atherosclerotic group: rats received the atherogenic diet; stem cells-treated group: rats were injected with CD34+ stem cells (6×106 cells in 0.5 mL PBS in rat tail vein) and maintained on the atherogenic diet; and resveratrol-treated group: rats were supplemented orally with resveratrol at a dose level 3 mg/kg per day and the atherogenic diet. After 12 weeks, rats were euthanized, blood samples were collected for separation of serum, and abdominal aortas were excised for further biochemical, molecular, and histopathological investigations. We used resveratrol, the well-established anti-atherosclerotic drug, as a benchmark to assess the efficacy of stem cell therapy. MSCs treatment revealed significant amelioration in both histopathological and biochemical patterns as evidenced by decreased foam cells formation, ICAM-1, VCAM, M-CSF, iNOS, COX-2, and TNF-α. We concluded that MSCs therapy significantly replaced the neointimal SMCs and decreased adhesion molecules as well as the oxidative and inflammatory markers in atherosclerosis.

Research Trends in the Efficacy of Stem Cell Therapy for Hepatic Diseases Based on MicroRNA Profiling.

Liver diseases, despite the organ’s high regenerative capacity, are caused by several environmental factors and persistent injuries. Their optimal treatment is a liver transplantation. However, this option is limited by donor shortages and immune response issues. Therefore, many researchers have been interested in identifying the therapeutic potential in treating irreversible liver damage based on stem cells and developing suitable therapeutic agents. Mesenchymal stem cells (MSCs), which are representative multipotent stem cells, are known to be highly potential stem cell therapy compared to other stem cells in the clinical trial worldwide. MSCs have therapeutic potentials for several hepatic diseases such as anti-fibrosis, proliferation of hepatocytes injured, anti-inflammation, autophagic mechanism, and inactivation of hepatic stellate cells. There are much data regarding clinical treatments, however, the data for examining the efficacy of stem cell treatment and the correlation between the stem cell engraftment and the efficacy in liver diseases is limited due to the lack of monitoring system for treatment effectiveness. Therefore, this paper introduces the characteristics of microRNAs (miRNAs) and liver disease-specific miRNA profiles, and the possibility of a biomarker that miRNA can monitor stem cell treatment efficacy by comparing miRNAs changed in liver diseases following stem cell treatment. Additionally, we also discuss the miRNA profiling in liver diseases when treated with stem cell therapy and suggest the candidate miRNAs that can be used as a biomarker that can monitor treatment efficacy in liver diseases based on MSCs therapy.