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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 -
BMJ Open Jun 2024To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal...
OBJECTIVE
To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal disorders and to describe the trials' clinical and design characteristics.
DESIGN
A systematic review of published trials and trials submitted to public registries.
DATA SOURCES
The databases Medline, Cochrane Library and McMaster; six public clinical registries. All searches were done until 31 January 2023.
ELIGIBILITY CRITERIA
Trials submitted to registries and completed before January 2021. Prospective interventional trials published in peer-reviewed journals.
DATA EXTRACTION AND SYNTHESIS
The first author searched for trials that had (1) posted trial results in a public registry, (2) presented results in a peer-reviewed publication and (3) submitted a pretrial protocol to a registry before publication. Other extracted variables included trial design, number of participants, funding source, follow-up duration and cell type.
RESULTS
In total 124 trials were found in registries and literature databases. Knee osteoarthritis was the most common indication. Of the 100 registry trials, 52 trials with in total 2 993 participants had neither posted results in the registry nor published results. Fifty-two of the registry trials submitted a protocol retrospectively. Forty-three of the 67 published trials (64%) had registered a pretrial protocol. Funding source was not associated with compliance with reporting requirements. A discrepancy between primary endpoints in the registry and publication was found in 16 of 25 trials. In 28% of trials, the treatment groups used adjuvant therapies. Only 39% of controlled trials were double-blinded.
CONCLUSIONS
A large proportion of trials failed to comply with statutory requirements for the registration and reporting of results, thereby increasing the risk of bias in outcome assessments. To improve confidence in the role of MSCs for musculoskeletal disorders, registries and medical journals should more rigorously enforce existing requirements for registration and reporting.
Topics: Humans; Registries; Musculoskeletal Diseases; Mesenchymal Stem Cell Transplantation; Clinical Trials as Topic; Guideline Adherence; Research Design; Mesenchymal Stem Cells
PubMed: 38925685
DOI: 10.1136/bmjopen-2023-081343 -
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 -
Journal of Translational Medicine Jun 2024The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients.
METHODS
We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis.
RESULTS
A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation.
CONCLUSION
This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.
Topics: Humans; COVID-19; Mesenchymal Stem Cell Transplantation; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; Mesenchymal Stem Cells
PubMed: 38851730
DOI: 10.1186/s12967-024-05358-6 -
European Review For Medical and... Aug 2023This systematic review focuses on which sources of mesenchymal stem cells (MSCs) are more beneficial for cartilage repair, specifically comparing umbilical cord...
The clinical outcomes of intra-articular injection of human umbilical cord blood-derived mesenchymal stem cells vs. bone marrow aspirate concentrate in cartilage regeneration: a systematic review.
OBJECTIVE
This systematic review focuses on which sources of mesenchymal stem cells (MSCs) are more beneficial for cartilage repair, specifically comparing umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and bone marrow aspirate concentrate (BMAC) in patients treated via a high tibial osteotomy (HTO) plus mesenchymal stem cells augmentation.
MATERIALS AND METHODS
PubMed, Scopus, Embase, Cochrane, and Web of Science were searched for literature published in English that compared the effects of hUCB-MSC amplification and BMAC transplantation in articular cartilage lesions of the human knee with at least 1 year of follow-up after surgery. The risk of bias in the included retrospective studies was assessed via the Coleman Methodology Score. The clinical prognosis was assessed based on the total clinical score, pain, function, and degree of cartilage repair.
RESULTS
The risk of bias in the included retrospective cohort studies was evaluated as fair. A formal meta-analysis of outcomes was not possible as the low evidence level and the nature of pooled retrospective studies introduced considerable heterogeneity. At an average of 1 year after surgery, two included studies reported that the ratio of normal and nearly normal cartilage repair assessed by International Cartilage Repair Society grading system (ICRS) grading in the second arthroscopy was higher in the hUCB-MSC group (Lee: 71.2% and 81.3%; Yang: 77.3%) than in the BMAC group (Lee: 45% and 40.5%; Yang: 56.8%). Ryu et al reported no significant difference between groups in the ICRS grade at 1-year post-operation (p = 0.655). Overall clinical outcome, pain and function were significantly improved at the last follow-up in both the BMAC group and the hUCB-MSC group, and there were no significant differences in these measures between groups.
CONCLUSIONS
This systematic review presents evidence that compared with BMAC injection, intra-articular hUCB-MSCs can induce significantly better tissue repair at 1 year after surgery, as assessed by the ICRS grade. Although there is only short-term follow-up evidence and a lack of histochemical evidence, our systematic review supports the recommendation to use hUCB-MSCs as the source of pluripotent stem cells for treating ICRS III cartilage lesions.
Topics: Humans; Bone Marrow; Cartilage, Articular; Fetal Blood; Injections, Intra-Articular; Mesenchymal Stem Cells; Pain; Retrospective Studies
PubMed: 37667930
DOI: 10.26355/eurrev_202308_33405 -
Regenerative Therapy Dec 2024Spinal cord injury is a lesion with high mortality and significant morbidities. After the primary injury, during six months, a cascade of secondary cellular and... (Review)
Review
Spinal cord injury is a lesion with high mortality and significant morbidities. After the primary injury, during six months, a cascade of secondary cellular and molecular events makes the lesion chronic. Recently, cell-based clinical trials as a new procedure have been gradually tested to improve the symptoms of patients. Each treatment method is associated with different adverse events. Based on the PRISMA flow diagram of the identified records, and after multistep screening, finally in 76 reviewed studies with 1633 cases and 189 controls, 64 types of adverse events in 12 categories were recorded in 45 studies. The most common adverse events were transient backache and meningism (90%) and cord malacia (80%). The cell therapy method in which the treatment was associated with more adverse events was Olfactory ensheathing cell and bone marrow mesenchymal stem cell combination therapy in 55%, and the adverse events were less with the embryonic stem cell in 2.33% of patients. In a meta-analysis, the total prevalence of adverse events in cell therapy was 19% and the highest pulled effect size belonged to urinary tract and localized adverse events. Also, the total prevalence of adverse events in 14 cell therapy methods was 18% and four cell types (neural stem cell, bone marrow hematopoietic stem cell, embryonic stem cell, and umbilical cord mesenchymal stem cell) had the most effect. None of the adverse events were reported on the 4 (life-threatening consequences) and 5 (death) grading scales. We concluded that the frequency of life-threatening adverse events following cell therapy clinical trials in chronic spinal cord injury patients is very scarce and can be ignored.
PubMed: 38694447
DOI: 10.1016/j.reth.2024.03.012 -
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 -
Frontiers in Endocrinology 2024The aim of this meta-analysis was to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of knee osteoarthritis (OA). (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The aim of this meta-analysis was to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) for the treatment of knee osteoarthritis (OA).
METHODS
The PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus and Web of Science databases were searched from inception to May 6, 2024 to identify randomized controlled trials that compared MSCs and placebo or other nonsurgical approaches for treating OA. Two investigators independently searched the literature and extracted data, and conventional meta-analyses were conducted with Review Manager 5.3. The outcomes included pain relief, functional improvement, and risk of adverse events (AEs).
RESULTS
A total of 18 articles were included. Overall, MSCs were superior to placebo in terms of relieving pain and improving function at the 12-month follow-up. However, the differences in treatment-related AEs were not significant.
CONCLUSION
MSCs may relieving pain and improving function of OA. The limitations of this study include the high heterogeneity of the included studies. Additionally, the follow-up time in the included studies was relatively short, so more clinical trials are needed to predict the long-term efficacy and safety of MSCs.
SYSTEMATIC REVIEW REGISTRATION
https://doi.org/10.17605/OSF.IO/5BT6E, identifier CRD42022354824.
Topics: Humans; Randomized Controlled Trials as Topic; Mesenchymal Stem Cell Transplantation; Osteoarthritis, Knee; Treatment Outcome; Osteoarthritis; Mesenchymal Stem Cells
PubMed: 38915896
DOI: 10.3389/fendo.2024.1366297 -
Journal of ISAKOS : Joint Disorders &... Jun 2024Orthobiologics has seen a renaissance over the last decade as an adjunct therapy during osteotomy due to the limited inherent regenerative potential of damaged... (Review)
Review
IMPORTANCE
Orthobiologics has seen a renaissance over the last decade as an adjunct therapy during osteotomy due to the limited inherent regenerative potential of damaged intraarticular tissues.
AIM OR OBJECTIVE
This systematic review aims to present the latest evidence regarding using orthobiologics with simultaneous high tibial osteotomy (HTO) for knee osteoarthritis. The results of this study may guide surgeons to improve their clinical results and clear the air regarding confusion over whether or not to add orthobiologics to HTO in clinical practice backed by scientific evidence.
EVIDENCE REVIEW
According to PRISMA guidelines a systematic search for relevant literature was performed in the PubMed (MEDLINE), Scopus, EMBASE, and Cochrane Library databases of all studies published in English from January 1990 to May 2023. The following search terms were entered into the title, abstract, and keyword fields: "knee" or "osteotomy" AND "valgus" or "varus" AND "regenerative medicine" or "PRP" or "mesenchymal stem cells" or "stem cells" or "BMAC" or "bone marrow" or "growth factors" or "umbilical cord blood-derived mesenchymal stem cell" or "stromal vascular fraction". The AMSTAR-2 checklist was used to confirm the quality of the systematic review. Randomised controlled trials (RCTs), prospective and retrospective comparative cohort studies, case-control studies, and case series were included. Studies that reported clinical outcomes in patients treated with knee osteotomy for varus/valgus knee with concomitant adjunction of regenerative treatment [Platelet-rich plasma (PRP), Adipose-derived stem cells (ADSC), Human Umbilical Cord Blood-Derived (HUCBD), Mesenchymal Stem Cells (MSC), bone marrow aspirate concentrate (BMAC), stromal vascular fraction (SVF)] were included. The outcome measures extracted from the studies were the KOOS score, Lysholm score, Subjective IKDC, WOMAC Score, KSS, Tegner, HSS, radiographic tibiofemoral angle, posterior tibial slope and complications. The current systematic review is registered in the PROSPERO Registry (CRD42023439379).
FINDINGS
Osteotomy for unicompartmental arthritis with adjunction of orthobiologics such as PRP, ADSC, HUCBD, MSC, BMAC, and SVF presents a consistent statistically significant clinical improvement compared to preoperative scores regardless of the treatment modality used and there were no notable complications associated with the use of these novel agents.
CONCLUSIONS AND RELEVANCE
Orthobiologics and knee osteotomies could improve outcomes in patients with knee osteoarthritis desiring Knee preservation surgeries. However, only a few studies are available on the topic to conclude anything with certainty, the patients included in the studies could not be disintegrated based on the grade of osteoarthritis (OA), type, dosage and frequency of administration of orthobiologic and type of additional surgical procedures used. Therefore, better-structured RCTs are required to implement this finding into routine Orthopaedic practice.
LEVEL OF EVIDENCE
Level 4.
PubMed: 38851324
DOI: 10.1016/j.jisako.2024.06.001 -
Frontiers in Neurology 2024Cell transplants as a treatment for Parkinson's disease have been studied for decades, and stem cells may be the most promising cell sources for this treatment. We aimed...
BACKGROUND
Cell transplants as a treatment for Parkinson's disease have been studied for decades, and stem cells may be the most promising cell sources for this treatment. We aimed to investigate whether stem cell transplantation contributes to the cure for Parkinson's disease and the factors that may influence the efficacy for this therapy.
METHODS
PubMed, Embase, Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and ChinaInfo were thoroughly searched to find controlled trials or randomized controlled trials performing stem cell transplantation in patients with Parkinson's disease. The pooled effects were analyzed to evaluate the weighted mean difference (WMD) with 95% confidence intervals.
RESULTS
Nine articles were identified including 129 individuals. Stem cell transplantation was an effective treatment for Parkinson's disease (WMD = -14.86; 95% CI: -16.62 to -13.10; < 0.00001), with neural stem cells, umbilical cord mesenchymal stem cells (UCMSCs), and bone marrow mesenchymal stem cells (BMMSCs) being effective cell sources for transplantation. Stem cell transplantation can be effective for at least 12 months, but its long-term effectiveness remains unknown due to the limited studies monitoring patients for more than 1 year, not to mention decades.
CONCLUSION
Data from controlled trials suggest that stem cell transplantation as a therapy for Parkinson's disease can be effective for at least 12 months. The factors that may influence its curative effect are time after transplantation and stem cell types.
SYSTEMATIC REVIEW REGISTRATION
(Registration ID: CRD42022353145).
PubMed: 38682036
DOI: 10.3389/fneur.2024.1329343