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Tissue Engineering. Part B, Reviews Oct 2023Critical-sized bone defects (CSBDs) represent a significant clinical challenge, stimulating researchers to seek new methods for successful bone reconstruction. The aim... (Review)
Review
Critical-sized bone defects (CSBDs) represent a significant clinical challenge, stimulating researchers to seek new methods for successful bone reconstruction. The aim of this systematic review is to assess whether bone marrow stem cells (BMSCs) combined with tissue-engineered scaffolds have demonstrated improved bone regeneration in the treatment of CSBD in large preclinical animal models. A search of electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) focused on large animal studies identified 10 articles according to the following inclusion criteria: (1) large animal models with segmental bone defects; (2) treatment with tissue-engineered scaffolds combined with BMSCs; (3) the presence of a control group; and (4) a minimum of a histological analysis outcome. Animal research: reporting of in Vivo Experiments guidelines were used for quality assessment, and Systematic Review Center for Laboratory animal Experimentation's risk of bias tool was used to define internal validity. The results demonstrated that tissue-engineered scaffolds, either from autografts or allografts, when combined with BMSCs provide improved bone mineralization and bone formation, including a critical role in the remodeling phase of bone healing. BMSC-seeded scaffolds showed improved biomechanical properties and microarchitecture properties of the regenerated bone when compared with untreated and scaffold-alone groups. This review highlights the efficacy of tissue engineering strategies for the repair of extensive bone defects in preclinical large-animal models. In particular, the use of mesenchymal stem cells, combined with bioscaffolds, seems to be a successful method in comparison to cell-free scaffolds.
PubMed: 36905366
DOI: 10.1089/ten.TEB.2022.0213 -
Systematic Reviews Nov 2023Stem cell sheet implantation offers a promising avenue for spinal cord injury (SCI) and is currently under investigation in pre-clinical in vivo studies. Nevertheless, a...
BACKGROUND
Stem cell sheet implantation offers a promising avenue for spinal cord injury (SCI) and is currently under investigation in pre-clinical in vivo studies. Nevertheless, a systematic review of the relevant literature is yet to be performed. Thus, this systematic review aims to explore the efficacy of stem cell sheet technology in treating SCI, as indicated by experimental animal model studies.
METHODS
We searched PubMed, EMBASE, and Web of Science. Manuscripts that did not pertain to in vivo pre-clinical studies and those published in non-English languages were excluded. A risk assessment for bias was performed using the SYRCLE tool. Extracted data were synthesized only qualitatively because the data were not suitable for conducting the meta-analysis.
RESULTS
Among the 847 studies retrieved from electronic database searches, seven met the inclusion criteria. Six of these studies employed a complete transection model, while one utilized a compression model. Stem cell sources included bone marrow mesenchymal stem cells, stem cells from human exfoliated deciduous teeth, and adipose-derived mesenchymal stem cells. In all included studies, stem cell sheet application significantly improved motor and sensory functional scores compared to intreated SCI rats. This functional recovery correlated with histological improvements at the injury site. All studies are at low risk of bias but certain domains were not reported by some or all of the studies.
CONCLUSION
The results of our systematic review suggest that stem cell sheets may be a feasible therapeutic approach for the treatment of SCI. Future research should be conducted on stem cell sheets in various animal models and types of SCI, and careful validation is necessary before translating stem cell sheets into clinical studies.
Topics: Animals; Humans; Rats; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Spinal Cord Injuries
PubMed: 38037129
DOI: 10.1186/s13643-023-02390-3 -
Journal of Orthopaedic Surgery and... Jun 2024In knee osteoarthritis (KOA), treatments involving knee injections of bone marrow-derived mesenchymal stem cells (BM-MSC), adipose tissue-derived mesenchymal stem cells... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In knee osteoarthritis (KOA), treatments involving knee injections of bone marrow-derived mesenchymal stem cells (BM-MSC), adipose tissue-derived mesenchymal stem cells (AD-MSC), or umbilical cord-derived mesenchymal stem cells (UC-MSC) have shown promise in alleviating symptoms. However, which types of mesenchymal stem cells (MSCs) have the best therapeutic outcomes remain uncertain.
METHOD
We systematically searched PubMed, OVID, Web of Science, and the Cochrane Library until January 1, 2024. The study evaluated five endpoints: Visual Analog Score (VAS) for Pain, Range of Motion (ROM), Whole-Organ Magnetic Resonance Imaging Score (WORMS), Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and adverse events (ADs). Standard meta-analysis and network meta-analysis were performed using Stata 16.0.
RESULTS
Fifteen studies involving 585 patients were included in the meta-analysis. Standard meta-analysis revealed significant improvements with MSCs in VAS score (P < 0.001), knee ROM (P < 0.001), and WOMAC (P < 0.016) compared to traditional therapy. In the network meta-analysis, autologous MSCs significantly improved VAS score [SMD = 2.94, 95% CI (1.90, 4.56)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to traditional therapy. Similarly, BM-MSC significantly improved VAS score [SMD = 0.31, 95% CI (0.11, 0.91)] and knee ROM [SMD = 0.26, 95% CI (0.08, 0.82)] compared to hyaluronic acid. However, compared with traditional therapy, autologous or allogeneic MSCs were associated with more adverse reactions [SMD = 0.11, 95% CI (0.02, 0.59)], [SMD = 0.13, 95% CI (0.002, 0.72)]. Based on the surface under the cumulative ranking results, autologous BM-MSC showed the most improvement in ROM and pain relief in KOA patients, UC-MSC (SUCRA 94.1%) were most effective for positive WORMS, and AD-MSC (SUCRA 70.6%) were most effective for WOMAC-positive patients.
CONCLUSION
MSCs transplantation effectively treats KOA patients, with autologous BM-MSC potentially offering more excellent benefits.
Topics: Humans; Osteoarthritis, Knee; Mesenchymal Stem Cell Transplantation; Treatment Outcome; Network Meta-Analysis; Mesenchymal Stem Cells; Adipose Tissue; Range of Motion, Articular; Umbilical Cord; Transplantation, Autologous; Male; Female; Middle Aged; Pain Measurement
PubMed: 38902778
DOI: 10.1186/s13018-024-04846-1 -
International Journal of Nanomedicine 2023The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration... (Review)
Review
The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration methods, nano-bioactive materials have become the optimal materials with excellent physicochemical properties and biocompatibility. Dental-derived mesenchymal stem cells (DMSCs) are a particular type of mesenchymal stromal cells (MSCs) with great potential in tissue regeneration and differentiation. This paper presents a review of the application of various nano-bioactive materials for the induction of differentiation of DMSCs in oral and maxillofacial restorations in recent years, outlining the characteristics of DMSCs, detailing the biological regulatory effects of various nano-materials on stem cells and summarizing the material-induced differentiation of DMSCs into multiple types of tissue-induced regeneration strategies. Nanomaterials are different and complementary to each other. These studies are helpful for the development of new nanoscientific research technology and the clinical transformation of tissue reconstruction technology and provide a theoretical basis for the application of nanomaterial-modified dental implants. We extensively searched for papers related to tissue engineering bioactive constructs based on MSCs and nanomaterials in the databases of PubMed, Medline, and Google Scholar, using keywords such as "mesenchymal stem cells", "nanotechnology", "biomaterials", "dentistry" and "tissue regeneration". From 2013 to 2023, we selected approximately 150 articles that align with our philosophy.
PubMed: 37753067
DOI: 10.2147/IJN.S418675 -
Knee Surgery & Related Research Mar 2024This systematic review aimed to evaluate the effects of concurrent cartilage procedures on cartilage regeneration when performed alongside high tibial osteotomy (HTO). (Review)
Review
PURPOSE
This systematic review aimed to evaluate the effects of concurrent cartilage procedures on cartilage regeneration when performed alongside high tibial osteotomy (HTO).
MATERIALS AND METHODS
The systematic review followed the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and Google Scholar, covering articles published until August 31, 2023.
RESULTS
Sixteen studies (1277 patients) revealed that HTO, with or without concurrent cartilage procedures, leads to cartilage regeneration based on the International Cartilage Repair Society (ICRS) grade during second-look arthroscopy. No concurrent procedure showed improvement in ICRS grade (mean difference: - 0.80 to - 0.49). Microfracture (mean difference: - 0.75 to - 0.22), bone marrow aspirate concentrate (BMAC) (mean difference: - 1.37 to - 0.67), and human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) (mean difference: - 2.46 to - 1.81) procedures also demonstrated positive outcomes. Clinical outcome assessments for each cartilage procedure were also improved during postoperative follow-up, and no specific complications were reported.
CONCLUSIONS
HTO with or without concurrent cartilage procedures promotes cartilage regeneration observed during second-look arthroscopy, with improved clinical outcomes. Future randomized controlled trials on the same topic, along with subsequent meta-analyses, are necessary for conclusive findings.
PubMed: 38549124
DOI: 10.1186/s43019-024-00221-w -
Stem Cells Translational Medicine Dec 2023The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a...
The development of extracellular vesicles (EVs) therapies has revolutionized personalized medicine, opening up new possibilities for treatment. EVs have emerged as a promising therapeutic tool within this field due to their crucial role in intercellular communication across various cell types and organisms. This systematic review aims to evaluate the therapeutic potential of oral mesenchymal stem cell (MSC)-derived EVs for bone regeneration, specifically focusing on findings from preclinical models. Sixteen articles meeting the inclusion criteria were selected following document analysis. The biological effects of oral MSC-derived EVs predominantly involve the upregulation of proteins associated with angiogenesis, and inflammation resolution, alongside the downregulation of proinflammatory cytokines. Moreover, these therapeutic agents have been found to contain a significant quantity of different molecules (proteins, lipids, DNA, microRNAs, etc) further contributing to their modulatory potential. The findings from this systematic review underscore that oral MSC-derived EVs, irrespective of their specific population, have the ability to enhance the osteogenic repair response in maxillary bone or periodontal defects. In summary, this systematic review highlights the promising potential of oral MSC-derived EVs for bone regeneration based on evidence from preclinical models. The comprehensive assessment of their biological effects and the presence of microRNAs underscores their therapeutic significance. These findings support the utilization of oral MSC-derived EVs in enhancing the osteogenic repair response in various maxillary bone or periodontal defects, providing insights into the mechanisms involved and potential therapeutic applications in the field of personalized medicine.
Topics: Mesenchymal Stem Cells; Extracellular Vesicles; MicroRNAs; Bone Regeneration; Osteogenesis
PubMed: 37715961
DOI: 10.1093/stcltm/szad059 -
Journal of Gynecologic Oncology Nov 2023The aim of this study is to determine the histologic presence of heterologous component as a prognostic factor in gynecologic carcinosarcoma through a systematic review... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study is to determine the histologic presence of heterologous component as a prognostic factor in gynecologic carcinosarcoma through a systematic review and meta-analysis.
METHODS
PubMed, Web of Science, and Embase were searched for publications. Studies that evaluated survival effect of sarcomatous component based on histology in human ovarian or uterine carcinosarcoma were included. Two authors independently reviewed the references based on eligibility criteria and extracted the data including primary tumor site, survival outcome, type of survival outcome, and proportion of each sarcomatous differentiation. The quality of each eligible study was assessed with Newcastle-Ottawa scale. Meta-analysis was conducted using a random-effects model to estimate hazard ratio (HR) and 95% confidence intervals (CIs) of survival outcome for carcinosarcoma with or without heterologous component.
RESULTS
Eight studies including 1,594 patients were identified. Overall proportion of carcinosarcoma with heterologous component was 43.3%. Presence of heterologous component was associated with worse overall survival (HR=1.81; 95% CI=1.15-2.85) but not with pooled recurrence-free survival and disease-free survival (HR=1.79; 95% CI=0.85-3.77). Removing multivariate analysis studies, early-stage studies, ovarian tumor study, or studies with large number of patient samples did not affect the significance between heterologous component and overall survival.
CONCLUSION
Gynecologic carcinosarcoma is histologically a biphasic tumor which comprise of epithelial and mesenchymal components. Our study emphasizes pathologic evaluation of heterologous component as a prognostic factor in gynecologic carcinosarcoma when all stages were considered.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42022298871.
Topics: Humans; Female; Prognosis; Carcinosarcoma; Disease-Free Survival; Multivariate Analysis; Ovarian Neoplasms; Uterine Neoplasms
PubMed: 37417301
DOI: 10.3802/jgo.2023.34.e73 -
Stem Cell Reviews and Reports May 2024The aim of the study is to determine the effectiveness of stem cells in scaffolds in the treatment of bone deficits, in regard of bone regeneration, safety,... (Review)
Review
The aim of the study is to determine the effectiveness of stem cells in scaffolds in the treatment of bone deficits, in regard of bone regeneration, safety, rehabilitation and quality of life in humans. The systematic review was conducted in accordance with PRISMA 2020. A systematic search was conducted in three search engines and two registries lastly in 29-9-2022.for studies of the last 15 years. The risk of bias was assessed with RoB-2, ROBINS- I and NIH Quality of Before-After (Pre-Post) Studies with no Control group. The certainty of the results was assessed with the GRADE assessment tool. Due to heterogeneity, the results were reported in tables, graphs and narratively. The study protocol was published in PROSPERO with registration number CRD42022359049. Of the 10,091 studies retrieved, 14 were meeting the inclusion criteria, and were qualitatively analyzed. 138 patients were treated with mesenchymal stem cells in scaffolds, showing bone healing in all cases, and even with better results than the standard care. The adverse events were mild in most cases and in accordance with the surgery received. When assessed, there was a rehabilitation of the deficit and a gain in quality of life was detected. Although the heterogeneity between the studies and the small number of patients, the administration of mesenchymal stem cells in scaffolds seems safe and effective in the regeneration of bone defects. These results pave the way for the conduction of more clinical trials, with greater number of participants, with more standardized procedures.
Topics: Humans; Bone Regeneration; Mesenchymal Stem Cells; Tissue Scaffolds; Mesenchymal Stem Cell Transplantation; Quality of Life; Clinical Trials as Topic
PubMed: 38407793
DOI: 10.1007/s12015-024-10696-5 -
Stem Cell Research & Therapy Sep 2023Recent studies have shown that mesenchymal stem cell (MSC) therapy has potential therapeutic effects for patients with end-stage liver diseases. However, a consensus on... (Meta-Analysis)
Meta-Analysis
Meta-analysis on last ten years of clinical injection of bone marrow-derived and umbilical cord MSC to reverse cirrhosis or rescue patients with acute-on-chronic liver failure.
BACKGROUND
Recent studies have shown that mesenchymal stem cell (MSC) therapy has potential therapeutic effects for patients with end-stage liver diseases. However, a consensus on the efficacy and safety of MSCs has not been reached.
METHODS
A systemic literature review was conducted by searching the Cochrane Library and PubMed databases for articles that evaluated the impact of MSC therapy on the outcomes among patients with end-stage liver disease. Various parameters, including pre- and post-treatment model of end-stage liver disease (MELD) score, serum albumin (ALB), total bilirubin (TB), coagulation function, aminotransferase, and survival rate, were evaluated.
RESULTS
This meta-analysis included a final total of 13 studies and 854 patients. The results indicated improved liver parameters following MSC therapy at different time points, including in terms of MELD score, TB level, and ALB level, compared with conventional treatment. Furthermore, the MSC treatment increased the overall survival rate among patients with liver cirrhosis and acute-on-chronic liver failure (ACLF). The changes in transaminase level and coagulation function differed between the different therapies at various post-treatment time points, indicating that MSC therapy provided no significant benefits in this regard. The further subgroup analysis stratified by liver background revealed that patients with ACLF benefit more from MSC therapy at most time points with improved liver function, including in terms of MELD score, TB level, and ALB level. In addition, no serious side effects or adverse events were reported following MSC therapy.
CONCLUSIONS
The meta-analysis results suggest that MSC therapy is safe and results in improved liver function and survival rates among patients with end-stage liver disease. The subgroup analysis stratified by liver background indicated that patients with ACLF benefit more from MSC therapy than patients with liver cirrhosis at most time points.
Topics: Humans; Acute-On-Chronic Liver Failure; End Stage Liver Disease; Bone Marrow; Liver Cirrhosis; Mesenchymal Stem Cells
PubMed: 37742014
DOI: 10.1186/s13287-023-03494-2 -
The Kaohsiung Journal of Medical... Jun 2024Autoimmune disease is characterized by the proliferation of harmful immune cells, inducing tissue inflammation and ultimately causing organ damage. Current treatments... (Review)
Review
Autoimmune disease is characterized by the proliferation of harmful immune cells, inducing tissue inflammation and ultimately causing organ damage. Current treatments often lack specificity, necessitating high doses, prolonged usage, and high recurrence rates. Therefore, the identification of innovative and safe therapeutic strategies is urgently required. Recent preclinical studies and clinical trials on inflammatory and autoimmune diseases have evidenced the immunosuppressive properties of mesenchymal stromal cells (MSCs). Studies have demonstrated that extracellular vesicles (EV) derived from MSCs can mitigate abnormal autoinflammation while maintaining safety within the diseased microenvironment. This study conducted a systematic review to elucidate the crucial role of MSC-EVs in alleviating autoimmune diseases, particularly focusing on their impact on the underlying mechanisms of autoimmune conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). By specifically examining the regulatory functions of microRNAs (miRNAs) derived from MSC-EVs, the comprehensive study aimed to enhance the understanding related to disease mechanisms and identify potential diagnostic markers and therapeutic targets for these diseases.
Topics: Humans; Mesenchymal Stem Cells; Extracellular Vesicles; Autoimmune Diseases; MicroRNAs; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Animals; Inflammatory Bowel Diseases; Immunomodulation
PubMed: 38712483
DOI: 10.1002/kjm2.12841