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Journal of Orthopaedic Surgery and... Apr 2016Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and... (Review)
Review
Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.
Topics: Cartilage, Articular; Humans; Mesenchymal Stem Cell Transplantation; Osteoarthritis; Regeneration; Tissue and Organ Harvesting
PubMed: 27072345
DOI: 10.1186/s13018-016-0378-x -
Stem Cells International 2021Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of... (Review)
Review
Bone regeneration is a complex and well-coordinated process that involves crosstalk between immune cells and resident cells in the injury site. Transplantation of mesenchymal stem cells (MSCs) is a promising strategy to enhance bone regeneration. Growing evidence suggests that macrophages have a significant impact on osteogenesis during bone regeneration. However, the precise mechanisms by which macrophage subtypes influence bone regeneration and how MSCs communicate with macrophages have not yet been fully elucidated. In this systematic literature review, we gathered evidence regarding the crosstalk between MSCs and macrophages during bone regeneration. According to the PRISMA protocol, we extracted literature from PubMed and Embase databases by using "mesenchymal stem cells" and "macrophages" and "bone regeneration" as keywords. Thirty-three studies were selected for this review. MSCs isolated from both bone marrow and adipose tissue and both primary macrophages and macrophage cell lines were used in the selected studies. In conclusion, anti-inflammatory macrophages (M2) have significantly more potential to strengthen bone regeneration compared with naïve (M0) and classically activated macrophages (M1). Transplantation of MSCs induced M1-to-M2 transition and transformed the skeletal microenvironment to facilitate bone regeneration in bone fracture and bone defect models. This review highlights the complexity between MSCs and macrophages, providing more insight into the polarized macrophage behavior in this evolving field of osteoimmunology. The results may serve as a useful reference for definite success in MSC-based therapy based on the critical interaction with macrophages.
PubMed: 34221025
DOI: 10.1155/2021/8835156 -
Journal of Endodontics Jun 2022MicroRNAs (miRNAs), small noncoding RNAs, control the translation of messenger RNAs into proteins. miRNAs have a crucial role in regulating the diverse biological... (Review)
Review
INTRODUCTION
MicroRNAs (miRNAs), small noncoding RNAs, control the translation of messenger RNAs into proteins. miRNAs have a crucial role in regulating the diverse biological processes of many physiological and pathological activities. The aim of this systematic review was to explore various functions of miRNAs in the regulation of dental pulp stem cell (DPSC) behavior.
METHODS
The articles were searched in PubMed, SCOPUS, and ISI Web of Science database using designated keywords. Full-length manuscripts published in English in peer-reviewed journals relevant to the role of miRNAs in DPSC functions were included and reviewed by 2 independent researchers.
RESULTS
The original search of the database generated 299 studies. A total of 102 duplicate studies were removed. After their exclusion, 48 studies were selected for review. miRNAs have shown to modulate the stemness and differentiation of various mesenchymal stem cells. The miRNAs expression profiles in DPSCs were differed compared with other cell types and have been demonstrated to regulate the levels of proteins crucial for promoting or inhibiting DPSC proliferation as well as differentiation. Further, miRNAs also modulate inflammatory processes in dental pulp.
CONCLUSION
miRNAs have various functions on the regulation of DPSCs and understanding these roles of miRNAs is crucial for the development of new therapeutics in regenerative dental medicine. With the advancing technologies, the utilization of miRNA technology could revolutionarily change the future of regenerative endodontics.
Topics: Cell Differentiation; Cell Proliferation; Cells, Cultured; Dental Pulp; Mesenchymal Stem Cells; MicroRNAs; Stem Cells
PubMed: 35271859
DOI: 10.1016/j.joen.2022.02.012 -
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 -
Journal of Experimental Orthopaedics Oct 2023Mesenchymal stem cells (MSCs) present a valuable treatment option for knee osteoarthritis with promising results. The purpose of the present study was to systematically... (Review)
Review
PURPOSE
Mesenchymal stem cells (MSCs) present a valuable treatment option for knee osteoarthritis with promising results. The purpose of the present study was to systematically review the clinical and functional outcomes following mesenchymal stem cell application focusing on early to moderate knee osteoarthritis.
METHODS
A systematic search was done using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in Pubmed, Scopus, Web of Science, and Cochrane Library databases. All Studies published between 2017 and March 2023 on patients treated with single mesenchymal stem cell injection for Kellgren-Lawrence grade I-III knee osteoarthritis reported on clinical and functional outcomes were included.
RESULTS
Twelve articles comprising 539 patients and 576 knees treated with a single intraarticular injection of MSCs for knee osteoarthritis were included in the current systematic review. In eligible studies, the reported outcomes were improved concerning patient-reported outcomes measures, knee function, pain relief, and quality of patient's life.
CONCLUSION
Based on high-level evidence studies, single intraarticular injection of MSCs is a safe, reliable, and effective treatment option for Kellgren-Lawrence grade I-III knee osteoarthritis. However, the lack of homogeneity in the included studies and the variance in MSCs sources and preparations should be noted.
LEVEL OF EVIDENCE
III.
PubMed: 37804354
DOI: 10.1186/s40634-023-00665-1 -
Neural Regeneration Research Jul 2024Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may...
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may improve symptoms, no treatment can cure or reverse the disease itself. Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson's disease. Mesenchymal stem cells are considered a promising option due to fewer ethical concerns, a lower risk of immune rejection, and a lower risk of teratogenicity. We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function, memory, and preservation of dopaminergic neurons in a Parkinson's disease animal model. We searched bibliographic databases (PubMed/MEDLINE, Embase, CENTRAL, Scopus, and Web of Science) to identify articles and included only peer-reviewed in vivo interventional animal studies published in any language through June 28, 2023. The study utilized the random-effect model to estimate the 95% confidence intervals (CI) of the standard mean differences (SMD) between the treatment and control groups. We use the systematic review center for laboratory animal experimentation's risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment. A total of 33 studies with data from 840 Parkinson's disease model animals were included in the meta-analysis. Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test. Among the stem cell types, the bone marrow MSCs with neurotrophic factor group showed largest effect size (SMD [95% CI] = -6.21 [-9.50 to -2.93], P = 0.0001, I2 = 0.0 %). The stem cell treatment group had significantly more tyrosine hydroxylase positive dopaminergic neurons in the striatum ([95% CI] = 1.04 [0.59 to 1.49], P = 0.0001, I2 = 65.1 %) and substantia nigra (SMD [95% CI] = 1.38 [0.89 to 1.87], P = 0.0001, I2 = 75.3 %), indicating a protective effect on dopaminergic neurons. Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route (SMD [95% CI] = -2.59 [-3.25 to -1.94], P = 0.0001, I2 = 74.4 %). The memory test showed significant improvement only in the intravenous route (SMD [95% CI] = 4.80 [1.84 to 7.76], P = 0.027, I2 = 79.6 %). Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson's disease. Further research is required to determine the optimal stem cell types, modifications, transplanted cell numbers, and delivery methods for these protocols.
PubMed: 38051903
DOI: 10.4103/1673-5374.387976 -
Stem Cell Reviews and Reports Mar 2022Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging from inhibition of tumor growth to cancer progression. A systematic review and meta-analysis is needed to clarify the effect of MSC-EVs on tumor growth to facilitate potential translation to clinical trials.
METHODS
A systematic search of the literature (MEDLINE, Embase, and BIOSIS databases to June 1, 2019) identified all pre-clinical controlled studies investigating the effect of MSC-EVs on tumor growth. Study selection and data extraction were performed in duplicate. Potential risk of bias was assessed using the SYRCLE tool. A random effects meta-analysis of reduction in tumor weight/volume (primary outcome) was performed.
RESULTS
We identified 29 articles and 22 reported data on tumor responses that were included for meta-analysis. Studies were associated with unclear risk of bias in a large proportion of domains in accordance with the SYRCLE tool for determining risk of bias in preclinical studies. A high risk of bias was not identified in any study. MSC-EVs had a mixed response on tumor progression with some studies reporting inhibition of tumor growth and others reporting tumor progression. Overall, MSC-EVs exerted a non-significant reduction in tumor growth compared to controls (standardized mean difference (SMD) -0.80, 95 % CI -1.64 to 0.03, p = 0.06, I = 87 %). Some studies reported increased tumor growth which aligned with their stated hypothesis and some interrogated mechanisms in cancer biology. EVs isolated from MSCs that overexpressed anti-tumor RNAs were associated with significant tumor reduction in meta-analysis (SMD - 2.40, 95 % CI -3.36 to -1.44, p < 0.001). Heterogeneity between studies was observed and included aspects of study design such as enrichment of MSC-EVs with specific anti-tumor molecules, tissue source of MSCs, method of EV isolation, characterization of MSCs and EVs, dosage and administration schedules, and tissue type and source of tumor cells studied.
CONCLUSIONS
MSC-EVs are associated with mixed effects on tumor growth in animal models of cancer. In studies where anti-tumor RNAs are packaged in EVs, a significant reduction in tumor growth was observed. Reducing heterogeneity in study design may accelerate our understanding of the potential effects of MSC-EVs on cancer. [274 words] Forest plot of MSC-EV effect on tumor growth accordinggenetic modification of EVs in animal studies identified from a systematicreview of the literature. All cohorts from studies with multiple interventiongroups are presented separately with control groups divided equally among thegroups. M, modified; H, hypoxia.
Topics: Animals; Disease Models, Animal; Extracellular Vesicles; Mesenchymal Stem Cells; Neoplasms
PubMed: 33860455
DOI: 10.1007/s12015-021-10163-5 -
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 -
International Journal of Molecular... May 2023Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their... (Review)
Review
Micro RNAs (miRNAs) are a type of non-coding RNA (ncRNA) and typically interact with specific target mRNAs through complementary base pairing, affecting their translation and/or stability. MiRNAs regulate nearly all cellular functions, including the cell fate of mesenchymal stromal cells (MSCs). It is now accepted that various pathologies arise at the stem level, and, in this scenario, the role played by miRNAs in the fate of MSCs becomes of primary concern. Here we have considered the existing literature in the field of miRNAs, MSCs and skin diseases, classified as inflammatory (such as psoriasis and atopic dermatitis-AD) and neoplastic (melanoma and non-melanoma-skin-cancer including squamous cell and basal cell carcinoma) diseases. In this scoping review article, the evidence recovered indicates that this topic has attracted attention, but it is still a matter of opinion. A protocol for this review was registered in PROSPERO with the registration number "CRD42023420245". According to the different skin disorders and to the specific cellular mechanisms considered (cancer stem cells, extracellular vesicles, inflammation), miRNAs may play a pro- or anti-inflammatory, as well as a tumor suppressive, or supporting, role, indicating a complex regulation of their function. It is evident that the mode of action of miRNAs is more than a switch on-off, and all the observed effects of their dysregulated expression must be checked in a detailed analysis of the targeted proteins. The involvement of miRNAs has been studied mainly for squamous cell carcinoma and melanoma, and much less in psoriasis and AD; different mechanisms have been considered, such as miRNAs included in extracellular vesicles derived both from MSCs or tumor cells, miRNAs involved in cancer stem cells formation, up to miRNAs as candidates to be new therapeutic tools.
Topics: Humans; MicroRNAs; Mesenchymal Stem Cells; Cell Differentiation; Skin Diseases; Neoplasms; Psoriasis
PubMed: 37239847
DOI: 10.3390/ijms24108502 -
Journal of Ophthalmic & Vision Research 2023This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed,... (Review)
Review
This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.
PubMed: 37600916
DOI: 10.18502/jovr.v18i3.13780