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Tissue Engineering. Part B, Reviews Feb 2021Clinical and animal studies have demonstrated efficacy of mesenchymal stem/stromal cells (MSCs) in cartilage repair. Although MSCs were originally predicated to mediate...
Clinical and animal studies have demonstrated efficacy of mesenchymal stem/stromal cells (MSCs) in cartilage repair. Although MSCs were originally predicated to mediate tissue repair through cellular differentiation and cell replacement, it is now recognized that MSCs exert most of their paracrine effects on tissue repair through the release of extracellular vesicles (EVs). In particular, 50-200 nm small EVs that also include exosomes carry a rich cargo of lipids, nucleic acids, and proteins, and have been reported to be therapeutically efficacious in various disease indications, including osteochondral injuries and osteoarthritis (OA). This systematic review aimed to assess the preclinical studies that used MSC exosomes for cartilage repair. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, PubMed and Cochrane Library databases were searched for relevant controlled preclinical animal studies. A total of 13 studies were identified, with the total sample size being 434. This included 378 (87.1%) mice or rats and 56 (12.9%) rabbits. According to Systematic Review Centre for Laboratory Animal Experimentation risk of bias assessment, all the studies presented with unclear-to-low risk in bias. In general, MSC exosomes were found to be efficacious in promoting repair and regeneration of osteochondral defects and alleviating OA degeneration. In most studies, exosome-treated animals displayed increased cellular proliferation, enhanced matrix deposition, and improved histological scores. Having assessed the relevant preclinical animal studies reported to date, this systematic review shows the therapeutic benefit of MSC exosome therapy in cartilage repair. Standardization of animal models and outcome measurements would be needed to facilitate more robust analysis and improve the validity of the results in future studies.
Topics: Animals; Cartilage; Exosomes; Mesenchymal Stem Cells; Mice; Osteoarthritis; Rabbits; Rats; Regeneration
PubMed: 32159464
DOI: 10.1089/ten.TEB.2019.0326 -
Translational Stroke Research Jun 2020There may be the potential to improve stroke recovery with mesenchymal stem cells (MSCs); however, questions about the efficacy and safety of this treatment remain. To... (Meta-Analysis)
Meta-Analysis
There may be the potential to improve stroke recovery with mesenchymal stem cells (MSCs); however, questions about the efficacy and safety of this treatment remain. To address these issues and inform future studies, we performed a preclinical and clinical systematic review of MSC therapy for subacute and chronic ischemic stroke. MEDLINE, Embase, the Cochrane Register of Controlled Trials, and PubMed were searched. For the clinical review, interventional and observational studies of MSC therapy in ischemic stroke patients were included. For the preclinical review, interventional studies of MSC therapy using in vivo animal models of subacute or chronic stroke were included. Measures of safety and efficacy were assessed. Eleven clinical and 76 preclinical studies were included. Preclinically, MSC therapy was associated with significant benefits for multiple measures of motor and neurological function. Clinically, MSC therapy appeared to be safe, with no increase in adverse events reported (with the exception of self-limited fever immediately following injection). However, the efficacy of treatment was less apparent, with significant heterogeneity in both study design and effect size being observed. Additionally, in the only randomized phase II study to date, efficacy of MSC therapy was not observed. Preclinically, MSC therapy demonstrated considerable efficacy. Although MSC therapy demonstrated safety in the clinical setting, efficacy has yet to be determined. Future studies will need to address the discordance in the continuity of evidence as MSC therapy has been translated from "bench-to-bedside".
Topics: Animals; Brain Ischemia; Humans; Ischemic Stroke; Mesenchymal Stem Cell Transplantation; Risk Factors; Translational Research, Biomedical; Treatment Outcome
PubMed: 31654281
DOI: 10.1007/s12975-019-00736-5 -
Heart, Lung & Circulation Jul 2023Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most well-studied and characterised stem cell types. This review was undertaken of the current available... (Meta-Analysis)
Meta-Analysis Review
AIM
Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most well-studied and characterised stem cell types. This review was undertaken of the current available phase II/III randomised clinical trials (RCTs) that delivered BM-MSCs to treat patients with cardiomyopathy, and to assess their performance.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed during the systematic review and meta-analysis. Eligible studies were reviewed, and their data charted. To assess the efficacy of BM-MSCs, the outcome was improvement in left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD).
RESULTS
The pooled weighted mean difference (WMD) showed that BM-MSCs treatment improved the 6MWD by 27.86 m (95% CI 0.11-55.6 m) compared with the control groups. The pooled WMD showed that BM-MSCs treatment improved the LVEF by 6.37% (95% CI 5.48%-7.26%) compared with the control groups.
CONCLUSION
BM-MSCs treatment is an effective intervention for managing patients with heart failure, but it requires larger and more robust clinical trials to support its routine use in clinics.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Heart Failure; Cardiomyopathies; Mesenchymal Stem Cells; Ventricular Function, Left; Bone Marrow Cells
PubMed: 36872163
DOI: 10.1016/j.hlc.2023.01.012 -
Arthroscopy : the Journal of... Jan 2021To evaluate the efficacy and safety of intra-articular mesenchymal stromal cells (MSCs) injections for knee osteoarthritis (OA) treatment. (Meta-Analysis)
Meta-Analysis
Intra-Articular Mesenchymal Stromal Cell Injections Are No Different From Placebo in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
PURPOSE
To evaluate the efficacy and safety of intra-articular mesenchymal stromal cells (MSCs) injections for knee osteoarthritis (OA) treatment.
METHODS
We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane Library through April 2020 to identify level I randomized controlled trials (RCTs) that evaluated the clinical efficacy of MSCs versus control treatments for knee OA. Outcomes were analyzed on an intention-to-treat basis with random-effects models.
RESULTS
A total of 13 RCTs were included in the meta-analysis. Compared with placebo, there was no significant difference in VAS for pain (mean difference [MD] 1.62, 95% confidence interval [CI -0.60 to 3.85), WOMAC pain score (MD 1.88, 95% CI -0.21 to 3.98), WOMAC function score (MD -0.67, 95% CI -6.54 to 5.19), or WOMAC stiffness score (MD 0.64, 95% CI -0.86 to 2.14) for MSCs. Moreover, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the minimum clinically important difference (MCID). Additionally, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and placebo groups for VAS for pain (relative risk [RR] 0.93, 95% CI 0.55 to 1.57) or WOMAC total score (RR 0.40, 95% CI 0.13 to 1.21). Compared with hyaluronic acid (HA), MSC injection was associated with significantly better improvement in VAS for pain (MD 2.00, 95% CI 0.94 to 3.07), WOMAC pain score (MD 4.58, 95% CI 0.49 to 8.67), WOMAC total score (MD 14.86, 95% CI 10.59 to 19.13), and WOMAC stiffness score (MD 1.85, 95% CI 0.02 to 3.69). However, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the MCID. Moreover, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and HA groups for WOMAC total score (RR 0.57, 95% CI 0.21 to 1.55). We also found that MSCs did not increase adverse events compared with HA and placebo.
CONCLUSIONS
Intra-articular MSC injection was not found to be superior to placebo in pain relief and functional improvement for patients with symptomatic knee OA. However, additional direct testing and combination trials of different type of cells, doses, and number of injections of MSCs are required to further enhance clinical decision making for people with symptomatic knee OA.
LEVEL OF EVIDENCE
I, meta-analysis of level I studies.
Topics: Humans; Injections, Intra-Articular; Knee Joint; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Minimal Clinically Important Difference; Osteoarthritis, Knee; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33098949
DOI: 10.1016/j.arthro.2020.10.016 -
Journal of Orthopaedic Research :... Apr 2024Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell... (Meta-Analysis)
Meta-Analysis
Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.
Topics: Humans; Osteoarthritis, Knee; Treatment Outcome; Injections, Intra-Articular; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Pain
PubMed: 37991925
DOI: 10.1002/jor.25724 -
Cytotherapy Apr 2021The therapeutic potential of naturally secreted micro- and nanoscale extracellular vesicles (EVs) makes them attractive candidates for regenerative medicine and... (Review)
Review
The therapeutic potential of naturally secreted micro- and nanoscale extracellular vesicles (EVs) makes them attractive candidates for regenerative medicine and pharmaceutical science applications. To date, the results of numerous publications have shown the practicality of using EVs to replace mesenchymal stromal cells (MSCs) or liposomes. This article presents a systematic review of pre-clinical studies conducted over the past decade of MSC-derived EVs (MSC-EVs) used in animal models of disease. The authors searched the relevant literature in the PubMed and Scopus databases (9358 articles), and 690 articles met the inclusion criteria. The eligible articles were placed in the following disease categories: autoimmune, brain, cancer, eye, gastrointestinal, heart, inflammation/transplantation, liver, musculoskeletal, pancreas, spinal cord and peripheral nervous system, respiratory system, reproductive system, skin, urinary system and vascular-related diseases. Next, the eligible articles were assessed for the rate of publication and global distribution, methodology of EV isolation and characterization, route of MSC-EV administration, length of follow-up, source of MSCs and animal species. The current review classifies and critically discusses the technical aspects of these MSC-EV animal studies and discusses potential relationships between methodological details and the effectiveness of MSC-EVs as reported by these pre-clinical studies.
Topics: Animals; Brain; Extracellular Vesicles; Inflammation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 33541780
DOI: 10.1016/j.jcyt.2020.12.009 -
Frontiers in Endocrinology 2023Studies have revealed that the transplantation of mesenchymal stem cells (MSCs) might be a potential star candidate for premature ovarian failure (POF) in animal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies have revealed that the transplantation of mesenchymal stem cells (MSCs) might be a potential star candidate for premature ovarian failure (POF) in animal experiments. However, individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis to explore the potential of using MSCs in the treatment of POF in animals.
METHODS
Seven databases were searched for studies exploring the effect of the transplantation of MSCs on POF in animal models. The PRISMA guideline was followed, and the methodological quality was ensured using SYRCLE's risk of bias tool. RevMan 5.4 and STATA 12.0 software was performed to meta-analysis.
RESULTS
In total, 37 studies involving 1,079 animals were included. Significant associations were found for MSCs with the levels of E2 (SMD 2.69 [95% CI 1.97, 3.41]), FSH (-2.02, [-2.74, -1.30]), primary follicles (2.04, [1.17, 2.92]), secondary follicles (1.93, [1.05, 2.81]), and primordial follicles (2.38, [1.19, 3.57]. Other outcomes, such as AMH, LH, INHB, antral follicles, growing follicles, mature follicles, and early antral were also found to be significant. There was no difference in FSH/LH, corpus leteum, follicles, and estruc cycle.
CONCLUSIONS
Our meta-analysis result indicated that the transplantation of MSCs might exert therapeutic effects on animal models of POF, and these effects might be associated with improving the disorder of the sexual cycle, modulating serum hormone expressions to a better state, and restoring ovarian function.
Topics: Female; Humans; Animals; Primary Ovarian Insufficiency; Ovarian Follicle; Menopause, Premature; Mesenchymal Stem Cells; Follicle Stimulating Hormone
PubMed: 37484938
DOI: 10.3389/fendo.2023.1165574 -
International Journal of Molecular... May 2023Back pain is the single leading cause of disability worldwide. Despite the prevalence and morbidity of lower back pain, we still lack a gold-standard treatment that... (Review)
Review
Back pain is the single leading cause of disability worldwide. Despite the prevalence and morbidity of lower back pain, we still lack a gold-standard treatment that restores the physiological function of degenerated intervertebral discs. Recently, stem cells have emerged as a promising strategy for regenerative therapy for degenerative disc disease. In this study, we review the etiology, pathogenesis, and developing treatment strategies for disc degeneration in low back pain with a focus on regenerative stem cell therapies. A systematic search of PubMed/MEDLINE/Embase/Clinical Trials.gov databases was conducted for all human subject abstracts or studies. There was a total of 10 abstracts and 11 clinical studies (1 RCT) that met the inclusion criteria. The molecular mechanism, approach, and progress of the different stem cell strategies in all studies are discussed, including allogenic bone marrow, allogenic discogenic cells, autologous bone marrow, adipose mesenchymal stem cells (MSCs), human umbilical cord MSC, adult juvenile chondrocytes, autologous disc derived chondrocytes, and withdrawn studies. Clinical success with animal model studies is promising; however, the clinical outcomes of stem cell regenerative therapy remain poorly understood. In this systematic review, we found no evidence to support its use in humans. Further studies on efficacy, safety, and optimal patient selection will establish whether this becomes a viable, non-invasive therapeutic option for back pain.
Topics: Adult; Animals; Humans; Low Back Pain; Intervertebral Disc Degeneration; Mesenchymal Stem Cell Transplantation; Back Pain; Intervertebral Disc
PubMed: 37240236
DOI: 10.3390/ijms24108893 -
Orthopaedics & Traumatology, Surgery &... Sep 2020Articular cartilage defect of the knee is a debilitating disease and marrow stimulation techniques (MST) is typically regarded as the first line of treatment for full... (Meta-Analysis)
Meta-Analysis Review
Expanded mesenchymal stem cell transplantation following marrow stimulation is more effective than marrow stimulation alone in treatment of knee cartilage defect: A systematic review and meta-analysis.
BACKGROUND
Articular cartilage defect of the knee is a debilitating disease and marrow stimulation techniques (MST) is typically regarded as the first line of treatment for full thickness cartilage lesions. However, the ability of MST to induce the repair of cartilage defects with fibrocartilage is limited, raising concerns about the durability of the repaired tissue. Mesenchymal stem cells (MSCs) provide an alternative means of treating cartilage defects. Expanded MSCs transplantation following MST has achieved great success in animal studies, but relevant clinical results are still lacking.
HYPOTHESIS
Expanded MSCs transplantation could be an effective adjunctive therapy following MST for knee cartilage defects.
PATIENTS AND METHODS
PubMed, EMBASE, and the Cochrane Library were systematically searched. This investigation considers articles that compare the effectiveness of expanded MSCs transplantation following MST (MSCs/MST) with that of MST alone for treating knee cartilage defects. Data on postoperative clinical outcomes were extracted. In an attempt to analyze trends over time in studies that report repeated measurements, an all time-points meta-analysis (ATM) was undertaken.
RESULTS
Five randomized controlled trials (RCTs) were included in this study. In a pooled analysis, the MSCs/MST group exhibited statistically significantly better postoperative international knee documentation committee subjective knee form (IKDC score) than the MST alone group during two years of follow-up (trend estimate through ATM, 0.27; 95% CI: 0.006 to 0.54). Lysholm scores were similarly favorable to MSCs/MST. The MSCs/MST group also yielded a statistically significantly higher magnetic resonance observation of cartilage repair tissue (MOCART) score at final follow-up (Mean Difference, 16.42; 95% CI: 4.44 to 28.40). No trial has identified serious adverse effects.
DISCUSSION
This meta-analysis demonstrate that expanded MSCs transplantation is a safe and effective adjunctive therapy. Further RCTs with long-term follow up and cost effectiveness analysis are needed.
LEVEL OF EVIDENCE
I, Systematic review and meta-analysis.
Topics: Bone Marrow; Cartilage, Articular; Knee Joint; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Randomized Controlled Trials as Topic; Transplantation, Autologous
PubMed: 32536601
DOI: 10.1016/j.otsr.2020.04.008 -
International Journal of Molecular... May 2023Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their... (Review)
Review
Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.
Topics: Humans; MicroRNAs; Mesenchymal Stem Cells; Cell Differentiation; Skin Diseases; Neoplasms; Psoriasis
PubMed: 37239847
DOI: 10.3390/ijms24108502