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Stem Cell Research & Therapy Apr 2023Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn's Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future.
SHORT CONCLUSION
MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs' efficacy.
Topics: Humans; Quality of Life; Mesenchymal Stem Cell Transplantation; Treatment Outcome; Mesenchymal Stem Cells; Rectal Fistula; Crohn Disease
PubMed: 37101285
DOI: 10.1186/s13287-023-03331-6 -
Stem Cell Research & Therapy Aug 2021We explored whether stem cell therapy was effective for animal models and patients with Crohn's disease (CD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We explored whether stem cell therapy was effective for animal models and patients with Crohn's disease (CD).
METHODS
We searched five online databases. The relative outcomes were analyzed with the aid of GetData Graph Digitizer 2.26 and Stata 16.0 software. The SYRCLE risk of bias tool and the MINORS tool were used to assess study quality.
RESULTS
We evaluated 46 studies including 28 animal works (n = 567) and 18 human trials (n = 360). In the animal studies, the disease activity index dramatically decreased in the mesenchymal stem cell (MSC) treatment groups compared to the control group. Rats and mice receiving MSCs exhibited longer colons [mice: standardized mean difference (SMD) 2.84, P = 0.000; rats: SMD 1.44, P = 0.029], lower histopathological scores (mice: SMD - 4.58, p = 0.000; rats: SMD - 1.41, P = 0.000) and lower myeloperoxidase levels (SMD - 6.22, P = 0.000). In clinical trials, stem cell transplantation reduced the CD activity index (SMD - 2.10, P = 0.000), the CD endoscopic index of severity (SMD - 3.40, P = 0.000) and simplified endoscopy score for CD (SMD - 1.71, P = 0.000) and improved the inflammatory bowel disease questionnaire score (SMD 1.33, P = 0.305) compared to control values. CD patients maintained high remission rates for 3-24 months after transplantation.
CONCLUSIONS
Stem cell transplantation is a valuable supplementary therapy for CD.
Topics: Animals; Crohn Disease; Hematopoietic Stem Cell Transplantation; Humans; Mesenchymal Stem Cells; Mice; Rats
PubMed: 34407875
DOI: 10.1186/s13287-021-02533-0 -
Osteoarthritis and Cartilage Sep 2022The aim of this systematic review was to assess the effects of stem cell-based therapies on the treatment of Temporomandibular Joint Osteoarthritis (TMJ-OA) and the... (Review)
Review
OBJECTIVES
The aim of this systematic review was to assess the effects of stem cell-based therapies on the treatment of Temporomandibular Joint Osteoarthritis (TMJ-OA) and the regeneration of cartilage/osteochondral defects.
METHODS
Data on preclinical studies evaluating the effectiveness of stem cell-based therapies for treating Temporomandibular Disorders (TMDs) were extracted from PubMed, Web of Science, and Cochrane Library and the grey literature by three independent reviewers. A manual search was performed in the databases, the reference list of review studies, and relevant journals in the field. Compliance with the ARRIVE guidelines was evaluated for quality assessment. SYRCLE's risk of bias tool for animal experimental studies was assessed to define internal validity.
RESULTS
After applying the inclusion and exclusion criteria, 10 studies were included in the qualitative synthesis. Regardless of cell origin, stem cell-based therapeutic approaches induced protective, anti-inflammatory, and chondroregenerative potential in the treatment of TMJ-OA. Regeneration of the cartilage layer on the surface of the condyle was achieved when stem cells were directly flushed into the defect or when delivered within a carrier.
CONCLUSION
Stem cell-based therapies may be considered a promising approach for the treatment of TMJ-OA and for the regeneration of full-thickness cartilage and osteochondral defects in the TMJ. Human studies shall be performed to validate these results found in animals.
Topics: Animals; Cartilage, Articular; Humans; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Regeneration; Temporomandibular Joint
PubMed: 35597373
DOI: 10.1016/j.joca.2022.05.006 -
International Journal of Stem Cells May 2018Mesenchymal stem cells (MSC) have emerged as breakthrough treatments for myocardial infarction. However, the efficacy of MSC remains unclear. The aim of the study was to... (Review)
Review
BACKGROUND AND OBJECTIVES
Mesenchymal stem cells (MSC) have emerged as breakthrough treatments for myocardial infarction. However, the efficacy of MSC remains unclear. The aim of the study was to evaluate treatment effect of MSC in terms of mechanical, regenerative, and clinical outcomes for patients with myocardial infarction (MI) using meta-analysis.
METHODS
A systematic search and critical review of MEDLINE, EMBASE, and Cochrane database literature published from inception through December 2017 was performed. The inclusion criteria were randomized controlled trials, studies on patients with myocardial infarction, and studies compared with placebo as a control group.
RESULTS
A total of 950 patients from 14 randomized placebo controlled trials were included in the final meta-analysis. MSC treatment showed benefits for mechanical, regenerative, and clinical outcomes. In terms of mechanical outcomes, the LVEF of the MSC treatment group increased by 3.84% (95% CI: 2.32~5.35, ²=43) and the effect was maintained for up to 24 months. Regenerative outcomes were measured by scar mass and WMSI. Scar mass was reduced by -1.13 (95% CI: -1.80 to -0.46, ²=71) and WMSI was reduced by -0.05 (95% CI: -0.07 to -0.03, ²=45) at 6 months after MSC treatment. Mortality rate and incidence of re-hospitalization for HF in MSC group patients trended toward reduced incidence compared to the control group, although this was not statistically significant because of the low event rate.
CONCLUSIONS
The findings of this meta-analysis indicate that MSCs can be beneficial in improving heart function in the treatment of MI. However, the efficacy of MSCs must be further explored through large randomized controlled trials based on rigorous research design.
PubMed: 29482311
DOI: 10.15283/ijsc17061 -
Stem Cell Research & Therapy Oct 2023Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell... (Meta-Analysis)
Meta-Analysis Review
AIM
Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell therapy for patients with liver cirrhosis are limited and these studies lack the consistency of treatment effects. This article aimed to systematically investigate the efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis.
METHOD
The data source included PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, from inception to May 2023. Literature was screened by the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Outcome indicators of the assessment included liver functions and adverse events. Statistical analysis was performed using Review Manager 5.4.
RESULTS
A total of 11 clinical trials met the selection criteria. The pooled analysis' findings demonstrated that both primary and secondary indicators had improved. Compared to the control group, infusion of mesenchymal stem cells significantly increased ALB levels in 2 weeks, 1 month, 3 months, and 6 months, and significantly decreased MELD score in 1 month, 2 months, and 6 months, according to a subgroup analysis using a random-effects model. Additionally, the hepatic arterial injection favored improvements in MELD score and ALB levels. Importantly, none of the included studies indicated any severe adverse effects.
CONCLUSION
The results showed that mesenchymal stem cell was effective and safe in the treatment of liver cirrhosis, improving liver function (such as a decrease in MELD score and an increase in ALB levels) in patients with liver cirrhosis and exerting protective effects on complications of liver cirrhosis and the incidence of hepatocellular carcinoma. Although the results of the subgroup analysis were informative for the selection of mesenchymal stem cells for clinical treatment, a large number of high-quality randomized controlled trials validations are still needed.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Liver Cirrhosis; Carcinoma, Hepatocellular; Liver Neoplasms
PubMed: 37864199
DOI: 10.1186/s13287-023-03518-x -
Epilepsia Jul 2022Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and... (Review)
Review
Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.
Topics: Animals; Drug Resistant Epilepsy; Epilepsies, Partial; Epilepsy; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells
PubMed: 35451066
DOI: 10.1111/epi.17266 -
International Journal of Molecular... Jul 2023Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and... (Review)
Review
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as "spinal cord injury," "stem cells," "stem cell therapy," "mesenchymal stem cells," and "traumatic spinal cord injury". Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Spinal Cord Injuries; Cell- and Tissue-Based Therapy; Myelin Sheath; Mesenchymal Stem Cells; Spinal Cord
PubMed: 37511478
DOI: 10.3390/ijms241411719 -
Current Stem Cell Research & Therapy 2017Since the discovery and isolation of a mesenchymal stem cell population from within the stromal vascular fraction (SVF) of adipose tissue, there has been a concerted...
BACKGROUND
Since the discovery and isolation of a mesenchymal stem cell population from within the stromal vascular fraction (SVF) of adipose tissue, there has been a concerted effort to discover the characteristics of these cells. Particular attention has been paid to their morphology, selfrenewal capacity, multi-lineage differentiation capabilities and, as is of greatest interest in this instance, their cell surface profile.
OBJECTIVES
The purpose of this study is to analyze and summarize the available literature that pertains to the cell surface characterization of adipose-derived stem cells (ASCs). The identification of a common set of positive and negative cell surface markers would allow for a much more consistent and reliable method of identifying this stem cell population both in vitro and in vivo.
SEARCH METHODS
The keywords "adipose-derived stem cells; stromal cells; surface markers" were searched in the following electronic databases: Medline, PubMed, ZETOC, Web of Knowledge, AMED, EMBASE, Ovid in process & other non-indexed citations and PsychINFO.
RESULTS
The most commonly reported positive markers were found to be CD90, CD44, CD29, CD105, CD13, CD34, CD73, CD166, CD10, CD49e and CD59, while the most commonly found negative markers were CD31, CD45, CD14, CD11b, CD34, CD19, CD56 and CD146. In addition, a number of other markers appeared in the literature including HLA-ABC, HLA-DR, SH2, SH3, STRO-1, VEGF2, vWF, ABCG2, SSEA-1 (CD15), PDGFR, alpha- SMA, c-Kit (CD117), OCT4+ and CCR5X (CD195).
CONCLUSION
A minimum panel of positive and negative markers for identifying ASCs can be recommended. The following markers should be positive: CD90, CD44, CD29, CD105, CD13, CD34, CD73, CD166, CD10, CD49e and CD59. The following markers should be negative: CD31, CD45, CD14, CD11b, CD19, CD56 and CD146. In addition to this, the positive expression of HLA- ABC and STRO- 1 should be seen along with the negative expression on HLA-DR. This review, however, has also found that there are a number of disagreements over the expression and existence of various markers, namely CD31, CD34, c- Kit (CD117) and STRO-1.
Topics: Adipocytes; Adipose Tissue; Animals; Biomarkers; Cell Differentiation; Humans; Mesenchymal Stem Cells; Stromal Cells
PubMed: 27133085
DOI: 10.2174/1574888X11666160429122133 -
Archives of Medical Research Jan 2021Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells capable of renewing themselves and differentiation in vitro into different kinds of tissues. In vivo...
INTRODUCTION
Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells capable of renewing themselves and differentiation in vitro into different kinds of tissues. In vivo hMSCs are sources of trophic factors modulating the immune system and inducing intrinsic stem cells to repair damaged tissues. Currently, there are multiple clinical trials (CT) using hMSCs for therapeutic purposes in a large number of clinical settings.
MATERIAL AND METHODS
The search strategy on clinicaltrials.gov has focused on the key term "Mesenchymal Stem Cells", and the inclusion and exclusion criteria were separated into two stages. Stage 1, CT on phases 1-4: location, the field of application, phase, and status. For stage 2, CT that have published outcome results: field of application, treatment, intervention model, source, preparation methods, and results.
RESULTS
By July 2020, there were a total of 1,138 registered CT. Most studies belong to either phase 2 (61.0%) or phase 1 (30.8%); most of them focused in the fields of traumatology, neurology, cardiology, and immunology. Only 18 clinical trials had published results: the most common source of isolation was bone marrow; the treatment varied from 1-200 M hMSCs; all of them have similar preparation methods; all of them have positive results with no serious adverse effects.
CONCLUSIONS
There appears to be a broad potential for the clinical use of hMSCs with no reported serious adverse events. There are many trials in progress, their future results will help to explore the therapeutic potential of these promising cellular sources of medicinal signals.
Topics: Cell Differentiation; Clinical Trials as Topic; Humans; Medicine; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 32977984
DOI: 10.1016/j.arcmed.2020.08.006 -
PloS One 2018Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.
METHODS
The electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.
RESULTS
Eleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.
CONCLUSION
MSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.
Topics: Acute Lung Injury; Animals; Disease Models, Animal; Evaluation Studies as Topic; Humans; Mesenchymal Stem Cell Transplantation; Paraquat; Pulmonary Edema
PubMed: 29566055
DOI: 10.1371/journal.pone.0194748