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International Journal of Molecular... Jun 2024The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the... (Review)
Review
The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the treatment of ischemic heart damage. Following PRISMA guidelines, we conducted electronic searches in MEDLINE, and EMBASE. We screened 592 studies, and included RCTs, observational studies, and cohort studies that examined the effect of hematopoietic stem cell therapy in adult patients with heart failure. Studies that involved pediatric patients, mesenchymal stem cell therapy, and non-heart failure (HF) studies were excluded from our review. Out of the 592 studies, 7 studies met our inclusion criteria. Overall, administration of hematopoietic stem cells (via intracoronary or myocardial infarct) led to positive cardiac outcomes such as improvements in pathological left-ventricular remodeling, perfusion following acute myocardial infarction, and NYHA symptom class. Additionally, combined death, rehospitalization for heart failure, and infarction were significantly lower in patients treated with bone marrow-derived hematopoietic stem cells. Our review demonstrates that hematopoietic stem cell administration can lead to positive cardiac outcomes for HF patients. Future studies should aim to increase female representation and non-ischemic HF patients.
Topics: Humans; Heart Failure; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Treatment Outcome
PubMed: 38928341
DOI: 10.3390/ijms25126634 -
International Journal of Molecular... Jun 2024Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context,... (Review)
Review
Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration.
Topics: Exosomes; Nerve Regeneration; Mesenchymal Stem Cells; Humans; Animals; Tissue Scaffolds; Peripheral Nerve Injuries; Mesenchymal Stem Cell Transplantation
PubMed: 38928194
DOI: 10.3390/ijms25126489 -
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 -
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 -
Cell Transplantation 2024Transplantation of mesenchymal stem cells (MSCs) is one of the hopeful treatments for spinal cord injury (SCI). Most current studies are in animals, and less in humans,... (Meta-Analysis)
Meta-Analysis
Transplantation of mesenchymal stem cells (MSCs) is one of the hopeful treatments for spinal cord injury (SCI). Most current studies are in animals, and less in humans, and the optimal transplantation strategy for MSCs is still controversial. In this article, we explore the optimal transplantation strategy of MSCs through a network meta-analysis of the effects of MSCs on SCI in animal models. PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Service System (SinoMed) databases were searched by computer for randomized controlled studies on MSCs for SCI. Two investigators independently completed the literature screening and data extraction based on the inclusion and exclusion criteria. RevMan 5.4 software was used to assess the quality of the included literature. Stata 16.0 software was used for standard meta-analysis and network meta-analysis. Standardized mean difference (SMD) was used for continuous variables to combine the statistics and calculate 95% confidence interval (95% CI). < 0.05 was considered a statistically significant difference. Cochrane's test and the value were used to indicate the magnitude of heterogeneity. A random-effects model was used if > 50% and < 0.10 indicated significant heterogeneity between studies, and conversely, a fixed-effects model was used. Evidence network diagrams were drawn based on direct comparisons between various interventions. The surface under the cumulative ranking curve area (SUCRA) was used to predict the ranking of the treatment effects of each intervention. A total of 32 animal studies were included in this article for analysis. The results of the standard meta-analysis showed that MSCs improved motor ability after SCI. The network meta-analysis showed that the best treatment effect was achieved for adipose tissue-derived mesenchymal stromal cells (ADMSCs) in terms of cell source and intrathecal (IT) in terms of transplantation modality. For transplantation timing, the best treatment effect was achieved when transplantation was performed in the subacute phase. The available literature suggests that IT transplantation using ADMSCs in the subacute phase may be the best transplantation strategy to improve functional impairment after SCI. Future high-quality studies are still needed to further validate the results of this study to ensure the reliability of the results.
Topics: Animals; Humans; Rats; Disease Models, Animal; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Network Meta-Analysis; Spinal Cord Injuries
PubMed: 38910431
DOI: 10.1177/09636897241262992 -
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 -
Cells Jun 2024Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory... (Review)
Review
Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Mesenchymal stromal/stem cells (MSCs) have emerged as a promising therapy for TMJ repair. This systematic review aims to consolidate findings from the preclinical animal studies evaluating MSC-based therapies, including MSCs, their secretome, and extracellular vesicles (EVs), for the treatment of TMJ cartilage/osteochondral defects and osteoarthritis (OA). Following the PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library databases were searched for relevant studies. A total of 23 studies involving 125 , 149 , 470 , and 74 were identified. Compliance with the ARRIVE guidelines was evaluated for quality assessment, while the SYRCLE risk of bias tool was used to assess the risk of bias for the studies. Generally, MSC-based therapies demonstrated efficacy in TMJ repair across animal models of TMJ defects and OA. In most studies, animals treated with MSCs, their derived secretome, or EVs displayed improved morphological, histological, molecular, and behavioral pain outcomes, coupled with positive effects on cellular proliferation, migration, and matrix synthesis, as well as immunomodulation. However, unclear risk in bias and incomplete reporting highlight the need for standardized outcome measurements and reporting in future investigations.
Topics: Animals; Temporomandibular Joint; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Temporomandibular Joint Disorders; Humans; Osteoarthritis; Extracellular Vesicles; Disease Models, Animal
PubMed: 38891122
DOI: 10.3390/cells13110990 -
Stem Cell Research & Therapy Jun 2024The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as...
AIMS AND OBJECTIVES
The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study.
METHOD
Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events.
RESULTS
In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte-keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP.
CONCLUSION
Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.
Topics: Adult; Female; Humans; Male; Platelet-Rich Plasma; Randomized Controlled Trials as Topic; Regenerative Medicine; Skin Diseases
PubMed: 38886861
DOI: 10.1186/s13287-024-03800-6 -
Archives of Dermatological Research Jun 2024The aim of this study was to assess, through a systematic review, the status of infrared thermography (IRT) as a diagnostic tool for skin neoplasms of the head and neck... (Review)
Review
The aim of this study was to assess, through a systematic review, the status of infrared thermography (IRT) as a diagnostic tool for skin neoplasms of the head and neck region and in order to validate its effectiveness in differentiating benign and malignant lesions. A search was carried out in the LILACS, PubMed/MEDLINE, SCOPUS, Web of Science and EMBASE databases including studies published between 2004 and 2024, written in the Latin-Roman alphabet. Accuracy studies with patients aged 18 years or over presenting benign and malignant lesions in the head and neck region that evaluated the performance of IRT in differentiating these lesions were included. Lesions of mesenchymal origin and studies that did not mention histopathological diagnosis were excluded. The systematic review protocol was registered in the PROSPERO database (CRD42023416079). Reviewers independently analyzed titles, abstracts, and full-texts. After extracting data, the risk of bias of the selected studies was assessed using the QUADAS - 2 tool. Results were narratively synthesized and the certainty of evidence was measured using the GRADE approach. The search resulted in 1,587 records and three studies were included. Only one of the assessed studies used static IRT, while the other two studies used cold thermal stress. All studies had an uncertain risk of bias. In general, studies have shown wide variation in the accuracy of IRT for differentiating between malignant and benign lesions, with a low level of certainty in the evidence for both specificity and sensitivity.
Topics: Humans; Thermography; Skin Neoplasms; Diagnosis, Differential; Head and Neck Neoplasms; Sensitivity and Specificity; Skin; Neck
PubMed: 38878184
DOI: 10.1007/s00403-024-03166-y -
Regional Anesthesia and Pain Medicine Jun 2024Knee osteoarthritis (OA) is a prevalent degenerative disease and causes disability, pain and imposes a substantial burden on patients. Conventional treatments for knee... (Review)
Review
BACKGROUND
Knee osteoarthritis (OA) is a prevalent degenerative disease and causes disability, pain and imposes a substantial burden on patients. Conventional treatments for knee OA show limited effectiveness. Consequently, innovative treatments, such as radiofrequency ablation (RFA) and intra-articular mesenchymal stem cells (IA MSC), have gained attention for addressing these limitations.
OBJECTIVE
We compared the efficacy of RFA and IA MSC for knee OA through a network meta-analysis (NMA).
EVIDENCE REVIEW
A literature search was conducted using PubMed, MEDLINE, Embase, Cochrane Library, Web of Science and handsearching. Randomized controlled trials (RCTs) comparing RFA or IA MSC to conventional treatments for knee OA were included. The primary outcomes comprised the pain score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The clinical outcomes were compared using a frequentist approach, and the treatments were ranked using the surface under the cumulative ranking curve (SUCRA) values.
FINDINGS
We included 34 RCTs (n=2371). Our NMA revealed that RFA and IA MSC were significantly more effective than conventional treatments in managing pain at both 3 and 6 months with moderate certainty. Specifically, RFA demonstrated the highest SUCRA values, indicating its superior efficacy. For WOMAC scores, both RFA and MSC showed significant improvements at 3 months, with RFA maintaining its lead at 6 months, although MSC did not display significant superiority at this stage.
CONCLUSIONS
This analysis suggests that RFA and MSC are resilient treatment options in knee OA. Despite some study heterogeneity, these treatments consistently outperformed conventional treatments, particularly in the short to mid-term, although with varying levels of certainty in their efficacy.
PROSPERO REGISTRATION NUMBER
CRD42023492299.
PubMed: 38876799
DOI: 10.1136/rapm-2024-105526