-
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 -
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 Molecular... Dec 2022Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton's... (Review)
Review
Mesenchymal Stem Cells (MSCs) are multipotent non-hematopoietic stromal cells found in different body tissues such as bone marrow, adipose tissue, periosteum, Wharton's jelly, umbilical cord, blood, placenta, amniotic fluid, and skin. The biological behavior of MSCs depends mainly on their interaction with the microenvironment in which they are found, whose quality deeply influences the regenerative and immunomodulatory properties of these cells. Several studies confirm the interaction between MSCs and inflammatory microenvironment in the pathogenesis of psoriasis, designating MSCs as an important factor driving psoriasis development. This review aims to describe the most recent evidence on how the inflammatory microenvironment that characterizes psoriasis influences the homeostasis of MSCs and how they can be used to treat the disease.
Topics: Pregnancy; Female; Humans; Cell Differentiation; Mesenchymal Stem Cells; Wharton Jelly; Umbilical Cord; Amniotic Fluid
PubMed: 36499401
DOI: 10.3390/ijms232315080 -
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 -
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 -
Therapeutic Advances in Respiratory... 2023In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the potential outburst of cytokine storm that damages the tissues and organs, especially the lungs. This leads to the manifestation of COVID-19 symptoms, such as pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and eventually death. Mesenchymal stromal/stem cells (MSCs) are currently one of hopeful approaches in treating COVID-19 considering its anti-inflammatory and immunomodulatory functions. On that account, the number of clinical trials concerning the use of MSCs for COVID-19 has been increasing. However, the number of systematic reviews and meta-analysis that specifically discuss its potential as treatment for the disease is still lacking. Therefore, this review will assess the safety and efficacy of MSC administration in COVID-19 patients.
OBJECTIVES
To pool evidence on the safety and efficacy of MSCs in treating COVID-19 by observing MSC-related adverse effects as well as evaluating its effects in reducing inflammatory response and improving pulmonary function.
DATA SOURCES AND METHODS
Following literature search across six databases and one trial register, full-text retrieval, and screening against eligibility criteria, only eight studies were included for data extraction. All eight studies evaluated the use of umbilical cord-derived mesenchymal stromal/stem cell (UC-MSC), infused intravenously. Of these eight studies, six studies were included in meta-analysis on the incidence of mortality, adverse events (AEs), and serious adverse events (SAEs), and the levels of C-reactive protein (CRP) and interleukin (IL)-6. Meta-analysis on pulmonary function was not performed due to insufficient data.
RESULTS
MSC-treated group showed significantly lower risk of mortality than the control group ( = 0.03). No statistical significance was observed on the incidence of AEs ( = 0.78) and SAEs ( = 0.44), and the levels of CRP ( = 0.06) and IL-6 ( = 0.09).
CONCLUSION
MSCs were safe for use, with lower risk of mortality and no association with AEs. Regarding efficacy, descriptive analysis showed indications of improvement on the inflammatory reaction, lung clearance, and oxygenation status despite the lack of statistical significance in meta-analysis of CRP and IL-6. Nevertheless, more studies are needed for affirmation.
REGISTRATION
This systematic review and meta-analysis was registered on the PROSPERO database (no. CRD42022307730).
Topics: Humans; COVID-19; SARS-CoV-2; Interleukin-6; Mesenchymal Stem Cell Transplantation; Cytokines; Mesenchymal Stem Cells
PubMed: 37128999
DOI: 10.1177/17534666231158276 -
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 -
Oncotarget Sep 2017Metastasis is the leading cause of cancer-related death and directly associates with cancer progression, resistance to anticancer therapy, and poor patient survival.... (Review)
Review
Metastasis is the leading cause of cancer-related death and directly associates with cancer progression, resistance to anticancer therapy, and poor patient survival. Current efforts focusing on the underlying molecular mechanisms of cancer metastasis attract a special attention to cancer researchers. The epithelial-mesenchymal transition is a complex of molecular program during embryogenesis, inflammation, tissue fibrosis, and cancer progression and metastasis. S100A4, an important member of S100 family proteins, functions to increase the tumor progression and metastasis. The molecular mechanisms of S100A4 involving in the progression and metastasis are diverse in various malignant tumors. Detection of S100A4 expression becomes a promising candidate biomarker in cancer early diagnosis and prediction of cancer metastasis and therefore, S100A4 may be a therapeutic target. This review summarized up to date advancement on the role of S100A4 in human cancer development, progression, and metastasis and the underlying molecular events and then strategies to target S100A4 expression experimentally.
PubMed: 29069865
DOI: 10.18632/oncotarget.18016 -
Stem Cells Translational Medicine Sep 2021Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this... (Meta-Analysis)
Meta-Analysis Review
Regenerative, cell-based therapy is a promising treatment option for diabetic kidney disease (DKD), which has no cure. To prepare for clinical translation, this systematic review and meta-analysis summarized the effect of cell-based interventions in DKD animal models and treatment-related factors modifying outcomes. Electronic databases were searched for original investigations applying cell-based therapy in diabetic animals with kidney endpoints (January 1998-May 2019). Weighted or standardized mean differences were estimated for kidney outcomes and pooled using random-effects models. Subgroup analyses tested treatment-related factor effects for outcomes (creatinine, urea, urine protein, fibrosis, and inflammation). In 40 studies (992 diabetic rodents), therapy included mesenchymal stem/stromal cells (MSC; 61%), umbilical cord/amniotic fluid cells (UC/AF; 15%), non-MSC (15%), and cell-derived products (13%). Tissue sources included bone marrow (BM; 65%), UC/AF (15%), adipose (9%), and others (11%). Cell-based therapy significantly improved kidney function while reducing injury markers (proteinuria, histology, fibrosis, inflammation, apoptosis, epithelial-mesenchymal-transition, oxidative stress). Preconditioning, xenotransplantation, and disease-source approaches were effective. MSC and UC/AF cells had greater effect on kidney function while cell products improved fibrosis. BM and UC/AF tissue sources more effectively improved kidney function and proteinuria vs adipose or other tissues. Cell dose, frequency, and administration route also imparted different benefits. In conclusion, cell-based interventions in diabetic animals improved kidney function and reduced injury with treatment-related factors modifying these effects. These findings may aid in development of optimal repair strategies through selective use of cells/products, tissue sources, and dose administrations to allow for successful adaptation of this novel therapeutic in human DKD.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 34106528
DOI: 10.1002/sctm.19-0419 -
Medicina (Kaunas, Lithuania) Dec 2022Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures... (Meta-Analysis)
Meta-Analysis Review
Background and Objectives: Human umbilical-cord-blood-derived mesenchymal stem cells (hUCB-MSCs) have recently been used in clinical cartilage regeneration procedures with the expectation of improved regeneration capacity. However, the number of studies using hUCB-MSCs is still insufficient, and long-term follow-up results after use are insufficient, indicating the need for additional data and research. We have attempted to prove the efficacy and safety of hUCB-MSC treatment in a comprehensive analysis by including all subjects with knee articular cartilage defect or osteoarthritis who have undergone cartilage repair surgery using hUCB-MSCs. We conducted a meta-analysis and demonstrated efficacy and safety based on a systematic review. Materials and Methods: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. For this study, we searched the PubMed, Embase, Web of Science, Scopus, and Cochrane Library literature databases up to June 2022. A total of seven studies were included, and quality assessment was performed for each included study using the Newcastle−Ottawa Quality Assessment Scale. Statistical analysis was performed on the extracted pooled clinical outcome data, and subgroup analyses were completed. Results: A total of 570 patients were included in the analysis. In pooled analysis, the final follow-up International Knee Documentation Committee (IKDC) score showed a significant increase (mean difference (MD), −32.82; 95% confidence interval (CI), −38.32 to −27.32; p < 0.00001) with significant heterogeneity (I2 = 93%, p < 0.00001) compared to the preoperative score. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at final follow-up were significantly decreased (MD, 30.73; 95% CI, 24.10−37.36; p < 0.00001) compared to the preoperative scores, with significant heterogeneity (I2 = 95%, p < 0.00001). The visual analog scale (VAS) score at final follow-up was significantly decreased (MD, 4.81; 95% CI, 3.17−6.46; p < 0.00001) compared to the preoperative score, with significant heterogeneity (I2 = 98%, p < 0.00001). Two studies evaluated the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and confirmed sufficient improvement. In a study analyzing a group treated with bone marrow aspiration concentrate (BMAC), there was no significant difference in clinical outcome or M-MOCART score, and the post-treatment International Cartilage Repair Society (ICRS) grade increased. Conclusion: This analysis demonstrated the safety, efficacy, and quality of repaired cartilage following hUCB-MSC therapy. However, there was no clear difference in the comparison with BMAC. In the future, comparative studies with other stem cell therapies or cartilage repair procedures should be published to support the superior effect of hUCB-MSC therapy to improve treatment of cartilage defect or osteoarthritis.
Topics: Humans; Osteoarthritis, Knee; Fetal Blood; Mesenchymal Stem Cell Transplantation; Cartilage, Articular; Mesenchymal Stem Cells; Arthroscopy; Treatment Outcome
PubMed: 36557003
DOI: 10.3390/medicina58121801