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International Journal of Molecular... Jan 2021Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations... (Meta-Analysis)
Meta-Analysis
Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords "nerve regeneration", "stem cells", "peripheral nerve injury", "rat", and "human" were used. Additionally, a "MeSH" research was performed in PubMed using the terms "stem cells" and "nerve regeneration". The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.
Topics: Animals; Cell Differentiation; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Nerve Regeneration; Peripheral Nerves; Rats; Schwann Cells; Sciatic Nerve
PubMed: 33430035
DOI: 10.3390/ijms22020572 -
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 -
Behavioural Brain Research Aug 2023Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research... (Review)
Review
BACKGROUND AND AIM
Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research was performed to develop pharmacological or non-pharmacological approaches to treat or improve AD complications. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. Recent evidence suggested that some of the therapeutic effects of MSCs are mediated by the secreted paracrine factors. These paracrine factors, called MSC- conditioned medium (MSC-CM), may stimulate endogenous repair, promote angio- and artery genesis, and reduce apoptosis through paracrine mechanisms. The current study aims to systematically review the advantages of MSC-CM to the development of research and therapeutic concepts for AD management.
MATERIAL AND METHODS
The present systematic review was performed using PubMed, Web of Science, and Scopus from April 2020 to May 2022 following the "Preferred Reporting Items for Systematic Reviews" (PRISMA) guidelines. The keywords, including "Conditioned medium OR Conditioned media OR Stem cell therapy" AND "Alzheimer's," was searched, and finally, 13 papers were extracted.
RESULTS
The obtained data revealed that MSC-CMs might positively affect neurodegenerative diseases prognosis, especially AD, through various mechanisms, including a decrease in neuro-inflammation, reduction of oxidative stress and Aβ formation, modulation of Microglia function and count, reduction of apoptosis, induction of synaptogenesis and neurogenesis. Also, the results showed that MSC-CM administration could significantly improve cognitive and memory function, increase the expression of neurotrophic factors, decrease the production of pro-inflammatory cytokines, improve mitochondrial function, reduce cytotoxicity, and increase neurotransmitter levels.
CONCLUSION
While inhibiting the induction of neuroinflammation could be considered the first therapeutic effect of CMs, the prevention of apoptosis could be regarded as the most crucial effect of CMs on AD improvement.
Topics: Humans; Alzheimer Disease; Culture Media, Conditioned; Neurodegenerative Diseases; Stem Cells; Mesenchymal Stem Cells
PubMed: 37311523
DOI: 10.1016/j.bbr.2023.114543 -
PloS One 2016Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in... (Review)
Review
OBJECTIVES
Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring.
DATA SOURCES
PubMed, Embase, the Cochrane Library and Google Scholar were searched.
METHODS
Controlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude.
RESULTS
Seven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η') and elastic modulus (G'), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds.
CONCLUSION
The results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies.
Topics: Animals; Cicatrix; Humans; Mesenchymal Stem Cells; Stem Cell Transplantation; Vocal Cords
PubMed: 27631373
DOI: 10.1371/journal.pone.0162349 -
Current Stem Cell Research & Therapy 2021Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating Heart Failure (HF). However, the effects of stem cell therapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating Heart Failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy are not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients.
METHODS
We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized Controlled Trials (RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model by the use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was safely assessed by death and rehospitalization and the secondary outcome was efficacy, which was assessed by six-minute walk distance and Left Ventricular Ejection Fraction (LVEF), Left Ventricular End-systolic Volume (LVESV), Left Ventricular End-diastolic Volume (LVEDV) and Brain Natriuretic Peptide (BNP).
RESULTS
A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT. MSCs transplantation significantly improved Left Ventricular Ejection Fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased Left Ventricular End-Systolic Volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, - 12.83], p<0.00001) and Left Ventricular End-Diastolic Volume (LVEDV) by 5.78 ml (MD [95% CI]=- 5.78[-12.00, 0.43], p=0.07), in the MSCs group, BNP was decreased by 133.51 pg/ml MD [95% CI]= - 133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group.
CONCLUSION
Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure are safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.
Topics: Heart Failure; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Function, Left
PubMed: 32867655
DOI: 10.2174/1574888X15999200820171432 -
Burns : Journal of the International... Mar 2021Mesenchymal stem cell (MSC) therapies are emerging as a promising strategy to promote tissue repair, and may extend their utility to burn care. This comprehensive review... (Review)
Review
AIM
Mesenchymal stem cell (MSC) therapies are emerging as a promising strategy to promote tissue repair, and may extend their utility to burn care. This comprehensive review of the extant literature, evaluated all in vivo studies, to elucidate the potential protective and therapeutic effect of MSCs in acute thermal skin burns.
METHODS
PubMed was systematically searched, according to PRISMA guidelines, and all relevant preclinical and clinical studies were included according to pre-specified eligibility criteria.
RESULTS
Forty-two studies were included in a qualitative synthesis, of which three were human and 39 were animal studies. The preclinical studies showed that MSCs can significantly reduce inflammation, burn wound progression and accelerate healing rate of acute burns. The underlying mechanisms are complex and not fully understood but paracrine modulators, such as immunomodulatory, antioxidative and trophic factors, seem to play important roles. Allogeneic MSC therapy has proved feasible in humans, and could allow for prompt treatment of acute burns in a clinical setting.
CONCLUSION
MSC therapy show positive results, regarding improved burn wound healing and immunologic response. However, most findings are based on small animal studies. Randomized clinical trials are warranted to investigate the regenerative effects in human burns before translating the findings into clinical practice.
Topics: Animals; Burns; Humans; Inflammation; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Wound Healing
PubMed: 33218945
DOI: 10.1016/j.burns.2020.04.012 -
Cells May 2022COPD is an incurable disorder, characterized by a progressive alveolar tissue destruction and defective mechanisms of repair and defense leading to emphysema. Currently,... (Meta-Analysis)
Meta-Analysis
COPD is an incurable disorder, characterized by a progressive alveolar tissue destruction and defective mechanisms of repair and defense leading to emphysema. Currently, treatment for COPD is exclusively symptomatic; therefore, stem cell-based therapies represent a promising therapeutic approach to regenerate damaged structures of the respiratory system and restore lung function. The aim of this study was to provide a quantitative synthesis of the efficacy profile of stem cell-based regenerative therapies and derived products in COPD patients. A systematic review and meta-analysis was performed according to PRISMA-P. Data from 371 COPD patients were extracted from 11 studies. Active treatments elicited a strong tendency towards significance in FEV1 improvement (+71 mL 95% CI -2−145; p = 0.056) and significantly increased 6MWT (52 m 95% CI 18−87; p < 0.05) vs. baseline or control. Active treatments did not reduce the risk of hospitalization due to acute exacerbations (RR 0.77 95% CI 0.40−1.49; p > 0.05). This study suggests that stem cell-based regenerative therapies and derived products may be effective to treat COPD patients, but the current evidence comes from small clinical trials. Large and well-designed randomized controlled trials are needed to really quantify the beneficial impact of stem cell-based regenerative therapy and derived products in COPD.
Topics: Emphysema; Humans; Pulmonary Disease, Chronic Obstructive; Stem Cells
PubMed: 35681492
DOI: 10.3390/cells11111797 -
Annals of Medicine and Surgery (2012) Dec 2017Stem cell regeneration is the holy grail of meniscal tissue repair. Currently, the best treatment is to preserve the original meniscus but if it fails, a partial... (Review)
Review
BACKGROUND
Stem cell regeneration is the holy grail of meniscal tissue repair. Currently, the best treatment is to preserve the original meniscus but if it fails, a partial meniscectomy is indicated to delay the onset of osteoarthritis.
MATERIALS AND METHODS
The authors present a systematic review to determine the up-to-date evidence underlying the use of mesenchymal stem cells for meniscal regeneration in humans. A search was conducted using the electronic databases of MEDLINE/Pubmed, Google scholar, and the Cochrane Collaboration. Search keywords included human, meniscus, stem cells and regeneration.
RESULTS
After screening 10 non-duplicate studies, 5 were identified based on title and abstract. 4 were included in the analysis. There were marked differences in the method of stem cell harvest techniques. 3 studies administered stem cells through percutaneous injection into the knee and 1 study used a collagen scaffold. MRI analysis, functional scores and safety were assessed and the longest follow-up period was 2 years. The Visual Analogue Score (VAS) was most commonly used to assess function and patients generally showed an improvement. There were no reported adverse events.
CONCLUSION
Despite positive results from animal models, there is currently a lack of evidence in humans to conclude that stem cells can form durable neotissue similar to original human meniscus. There is a need for standardisation of protocol before further trials are considered. Initial outcomes from human studies are promising and mesenchymal stem cells may play an important role in meniscal repair in years to come.
PubMed: 29062478
DOI: 10.1016/j.amsu.2017.09.018 -
Current Stem Cell Research & Therapy Feb 2018Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments.
OBJECTIVE
We systematically reviewed clinical trials of MSCs for cartilage repair and provide an overview of the literature in this area here. MEDLINE, Embase, CENTRAL, clinicaltrials.gov and Open- Grey were searched for controlled trials and case series with >5 patents involving MSC therapy for cartilage repair. The controlled trials were meta-analysed and the primary outcome measure was improvement in pain over the control group. A narrative synthesis was composed for the case series.
RESULTS
A significant reduction in pain was found with the use of MSCs over controls: Standardised mean difference=-1.27 (95% Confidence intervals -1.95 to -0.58). However, the data was extremely heterogeneous with I2=95%, this may be attributed to differing therapies, clinical indication for treatment and joints treated amongst others. Case series showed improvements in treated patients with a variety of differing treatments and by many outcomes. There were no severe adverse outcomes found across all studies that could be attributed to MSCs, implying their safety.
CONCLUSION
We conclude that MSCs have significant potential for the treatment of OA, however, larger, more consistent trials are needed for conclusive analysis.
Topics: Clinical Trials as Topic; Female; Humans; Male; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Regenerative Medicine; Treatment Outcome
PubMed: 28914207
DOI: 10.2174/1574888X12666170915120620 -
Current Stem Cell Research & Therapy 2022Adult stem cells like mammary and mesenchymal stem cells have received significant attention because these stem cells possess therapeutic potential in treating many...
Adult stem cells like mammary and mesenchymal stem cells have received significant attention because these stem cells possess therapeutic potential in treating many animal diseases. These cells can be administered in an autologous or allogenic fashion, either freshly isolated from the donor tissue or previously cultured and expanded in vitro. The expansion of adult stem cells is a prerequisite before therapeutic application because sufficient numbers are required in dosage calculation. Stem cells directly and indirectly (by secreting various growth factors and angiogenic factors called secretome) act to repair and regenerate injured tissues. Recent studies on mammary stem cells showed in vivo and in vitro expansion ability by removing the blockage of asymmetrical cell division. Compounds like purine analogs (xanthosine, xanthine, and inosine) or hormones (progesterone and bST) help increase stem cell population by promoting cell division. Such methodology of enhancing stem cell number, either in vivo or in vitro, may help in preclinical studies for translational research like treating diseases such as mastitis. The application of mesenchymal stem cells has also been shown to benefit mammary gland health due to the 'homing' property of stem cells. In addition to that, the multiple positive effects of stem cell secretome are on mammary tissue; healing and killing bacteria is novel in the production of quality milk. This systematic review discusses some of the studies on stem cells that have been useful in increasing the stem cell population and increasing mammary stem/progenitor cells. Finally, we provide insights into how enhancing mammary stem cell population could potentially increase terminally differentiated cells, ultimately leading to more milk production.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Female; Humans; Mammary Glands, Animal; Milk; Stem Cells
PubMed: 34348628
DOI: 10.2174/1574888X16666210804111516