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Medicina (Kaunas, Lithuania) Jan 2023Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic... (Review)
Review
Efficacy of Adipose-Derived Mesenchymal Stem Cells and Stromal Vascular Fraction Alone and Combined to Biomaterials in Tendinopathy or Tendon Injury: Systematic Review of Current Concepts.
Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is often suboptimal and impaired. This is due to the inherent scarce ability of tendon tissue to repair and return itself to the original structure. Recently, Adipose-derived mesenchymal stem cells (ADSC) and stromal vascular fraction (SVF) have gained a central interest in the scientific community, demonstrating their effectiveness in treatments of acute and chronic tendon disorders in animals and humans. Either enzymatic or mechanical procedures to obtain ADSC and SVF have been described and used in current clinical practice. However, no unified protocols and processes have been established. This systematic review aims at providing a comprehensive update of the literature on the clinical application of ADSC enzymatically or mechanically processed to obtain SVF, alone and in association with biomaterials in the local treatment of tendinopathy and tendon injury in vivo, in animal models and humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Thirty-two articles met our inclusion criteria, with a total of 18 studies in animals, 10 studies in humans and 4 studies concerning the application of biomaterials in vivo in animals. The review of the literature suggests that ADSC/SVF therapy can represent a promising alternative in tendonregenerative medicine for the enhancement of tendon healing. Nevertheless, further investigations and randomized control trials are needed to improve the knowledge, standardize the procedures and extend the consensus on their use for such applications.
Topics: Animals; Humans; Stromal Vascular Fraction; Biocompatible Materials; Mesenchymal Stem Cells; Tendinopathy; Tendons
PubMed: 36837474
DOI: 10.3390/medicina59020273 -
Herz Sep 2020Mesenchymal stem cell (MSC) treatment has emerged as an important adjunct therapy for heart failure. However, the use of MSC to treat heart failure has not been well... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mesenchymal stem cell (MSC) treatment has emerged as an important adjunct therapy for heart failure. However, the use of MSC to treat heart failure has not been well established. We conducted a systematic review and meta-analysis to evaluate the efficacy of MSC treatment for heart failure.
METHODS
PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) assessing the influence of MSC treatment on cardiac function in heart failure were included in this analysis. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using the fixed-effect model or random-effect model when appropriate.
RESULTS
Six RCTs involving 625 patients were included in the meta-analysis. Compared with control interventions in heart failure patients, MSC treatment had no significant influence on cardiovascular death (RR = 0.76; 95% CI = 0.38-1.52; p = 0.43); however, it was associated with significantly increased left ventricular ejection fraction (LVEF; mean = 9.64; 95% CI = 7.56-11.71; p < 0.00001) and reduced rehospitalization rate (RR = 0.41; 95% CI = 0.23-0.73; p = 0.003). In addition, no significant difference between the two groups was observed for the incidence of myocardial infarction (RR = 0.72; 95% CI = 0.10-5.02; p = 0.74), the recurrence of heart failure (RR = 0.88; 95% CI = 0.28-2.81; p = 0.83), and total death (RR = 0.68; 95% CI = 0.37-1.25; p = 0.21).
CONCLUSION
Although MSC treatment can significantly improve LVEF and reduce rehospitalization rates, it does not have a significant influence on cardiovascular death, myocardial infarction, heart failure, and total death.
Topics: Heart Failure; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Stroke Volume; Ventricular Function, Left
PubMed: 30341444
DOI: 10.1007/s00059-018-4762-7 -
Stem Cell Research & Therapy Sep 2022Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal... (Meta-Analysis)
Meta-Analysis Review
The optimal transplantation strategy of umbilical cord mesenchymal stem cells in spinal cord injury: a systematic review and network meta-analysis based on animal studies.
OBJECTIVE
Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal transplantation strategy are still unclear. Therefore, exploring the optimal treatment strategy of UCMSCs in animal studies by systematic review can provide reference for the development of animal studies and clinical research in the future.
METHODS
Databases of PubMed, Ovid-Embase, Web of Science, CNKI, WanFang, VIP, and CBM were searched for the literature in February 11, 2022. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction.
RESULTS AND DISCUSSION
A total of 40 animal studies were included for combined analysis. In different subgroups, the results of traditional meta-analysis and network meta-analysis were consistent, that is, the therapeutic effect of high-dose (≥ 1 × 10) transplantation of UCMSCs was significantly better than that of low dose (< 1 × 10), the therapeutic effect of local transplantation of UCMSCs was significantly better than that of intravenous transplantation, and the therapeutic effect of subacute transplantation of UCMSCs was significantly better than that of acute and chronic transplantation. However, in view of the inherent risk of bias and limited internal and external validity of the current animal studies, more high-quality, direct comparison studies are needed to further explore the optimal transplantation strategy for UCMSCs in the future.
Topics: Animals; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Network Meta-Analysis; Spinal Cord Injuries; Umbilical Cord
PubMed: 36056386
DOI: 10.1186/s13287-022-03103-8 -
Plastic and Reconstructive Surgery Mar 2020Autologous fat grafting is a dynamic modality used in plastic surgery as an adjunct to improve functional and aesthetic form. However, current practices in fat grafting...
BACKGROUND
Autologous fat grafting is a dynamic modality used in plastic surgery as an adjunct to improve functional and aesthetic form. However, current practices in fat grafting for soft-tissue augmentation are plagued by tremendous variability in long-term graft retention, resulting in suboptimal outcomes and repetitive procedures. This systematic review identifies and critically appraises the evidence for various enrichment strategies that can be used to augment and improve the viability of fat grafts.
METHODS
A comprehensive literature search of the Medline and PubMed databases was conducted for animal and human studies published through October of 2017 with multiple search terms related to adipose graft enrichment agents encompassing growth factors, platelet-rich plasma, adipose-derived and bone marrow stem cells, gene therapy, tissue engineering, and other strategies. Data on level of evidence, techniques, complications, and outcomes were collected.
RESULTS
A total of 1382 articles were identified, of which 147 met inclusion criteria. The majority of enrichment strategies demonstrated positive benefit for fat graft survival, particularly with growth factors and adipose-derived stem cell enrichment. Platelet-rich plasma and adipose-derived stem cells had the strongest evidence to support efficacy in human studies and may demonstrate a dose-dependent effect.
CONCLUSIONS
Improved understanding of enrichment strategies contributing to fat graft survival can help to optimize safety and outcomes. Controlled clinical studies are lacking, and future studies should examine factors influencing graft survival through controlled clinical trials in order to establish safety and to obtain consistent outcomes.
Topics: Adipose Tissue; Animals; Autografts; Body Contouring; Esthetics; Graft Survival; Humans; Mesenchymal Stem Cell Transplantation; Models, Animal; Platelet-Rich Plasma; Transplantation, Autologous; Treatment Outcome
PubMed: 32097333
DOI: 10.1097/PRS.0000000000006557 -
Cell and Tissue Research Mar 2021Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic... (Review)
Review
Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed.
Topics: Animals; Cicatrix, Hypertrophic; Humans; Keloid; Mesenchymal Stem Cell Transplantation; Treatment Outcome; Wound Healing
PubMed: 33386995
DOI: 10.1007/s00441-020-03361-z -
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 -
Journal of Translational Medicine Jan 2021The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial... (Meta-Analysis)
Meta-Analysis Review
The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial-mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial-mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.
Topics: Cell Line, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Neoplasm Grading; Prognosis; Prostatic Neoplasms; Tumor Microenvironment
PubMed: 33413466
DOI: 10.1186/s12967-020-02644-x -
Oxidative Medicine and Cellular... 2018Based on animal studies, adult mesenchymal stromal cells (MSCs) are promising for the treatment of pancreatitis. However, the best type of this form of cell therapy and... (Review)
Review
BACKGROUND
Based on animal studies, adult mesenchymal stromal cells (MSCs) are promising for the treatment of pancreatitis. However, the best type of this form of cell therapy and its mechanism of action remain unclear.
METHODS
We searched the PubMed, Web of Science, Scopus, Google Scholar, and Clinical Trials.gov websites for studies using MSCs as a therapy for both acute and chronic pancreatitis published until September 2017.
RESULTS
We identified 276 publications; of these publications, 18 met our inclusion criteria. In animal studies, stem cell therapy was applied more frequently for acute pancreatitis than for chronic pancreatitis. No clinical trials were identified. MSC therapy ameliorated pancreatic inflammation in acute pancreatitis and pancreatic fibrosis in chronic pancreatitis. Bone marrow and umbilical cord MSCs were the most frequently administered cell types. Due to the substantial heterogeneity among the studies regarding the type, source, and dose of MSCs used, conducting a meta-analysis was not feasible to determine the best type of MSCs.
CONCLUSION
The available data were insufficient for determining the best type of MSCs for the treatment of acute or chronic pancreatitis; therefore, clinical trials investigating the use of MSCs as therapy for pancreatitis are not warranted.
Topics: Animals; Cell- and Tissue-Based Therapy; Disease Models, Animal; Humans; Mesenchymal Stem Cells; Pancreatitis, Chronic
PubMed: 29743979
DOI: 10.1155/2018/3250864 -
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 -
Stem Cell Research & Therapy Jul 2021Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Over the past decades, many studies focused on mesenchymal stem cells (MSCs) therapy for bone regeneration. Due to the efficiency of topical application has been widely dicussed and systemic application was also a feasible way for new bone formation, the aim of this study was to systematically review systemic therapy of MSCs for bone regeneration in pre-clinical studies.
METHODS
The article search was conducted in PubMed and Embase databases. Original research articles that assessed potential effect of systemic application of MSCs for bone regeneration in vivo were selected and evaluated in this review, according to eligibility criteria. The efficacy of MSC systemic treatment was analyzed by random effects meta-analysis, and the outcomes were expressed in standard mean difference (SMD) and its 95% confidence interval. Subgroup analyses were conducted on animal species and gender, MSCs types, frequency and time of injection, and bone diseases.
RESULTS
Twenty-three articles were selected in this review, of which 21 were included in meta-analysis. The results showed that systemic therapy increased bone mineral density (SMD 3.02 [1.84, 4.20]), bone volume to tissue volume ratio (2.10 [1.16, 3.03]), and the percentage of new bone area (7.03 [2.10, 11.96]). Bone loss caused by systemic disease tended to produce a better response to systemic treatment (p=0.05 in BMD, p=0.03 in BV/TV).
CONCLUSION
This study concluded that systemic therapy of MSCs promotes bone regeneration in preclinical experiments. These results provided important information for the systemic application of MSCs as a potential application of bone formation in further animal experiments.
Topics: Animals; Bone Regeneration; Bone and Bones; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteogenesis
PubMed: 34215342
DOI: 10.1186/s13287-021-02456-w