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British Medical Bulletin Jun 2023Chronic low back pain, common from the sixth decade, negatively impacts the quality of life of patients and health care systems. Recently, mesenchymal stem cells (MSCs)...
BACKGROUND
Chronic low back pain, common from the sixth decade, negatively impacts the quality of life of patients and health care systems. Recently, mesenchymal stem cells (MSCs) have been introduced in the management of degenerative discogenic pain. The present study summarizes the current knowledge on the effectiveness of MSCs in patients with discogenic back pain.
SOURCES OF DATA
We performed a systematic review of the literature following the PRISMA guidelines. We searched PubMed and Google Scholar database, and identified 14 articles about management of chronic low back pain with MSCs injection therapy. We recorded information on type of stem cells employed, culture medium, clinical scores and MRI outcomes.
AREAS OF AGREEMENT
We identified a total of 303 patients. Ten studies used bone marrow stem cells. In the other four studies, different stem cells were used (of adipose, umbilical, or chondrocytic origin and a pre-packaged product). The most commonly used scores were Visual Analogue Scale and Oswestry Disability Index.
AREAS OF CONTROVERSY
There are few studies with many missing data.
GROWING POINTS
The studies analysed demonstrate that intradiscal injections of MSCs are effective on discogenic low-back pain. This effect may result from inhibition of nociceptors, reduction of catabolism and repair of injured or degenerated tissues.
AREAS TIMELY FOR DEVELOPING RESEARCH
Further research should define the most effective procedure, trying to standardize a single method.
Topics: Humans; Low Back Pain; Quality of Life; Treatment Outcome; Mesenchymal Stem Cells; Magnetic Resonance Imaging
PubMed: 37164906
DOI: 10.1093/bmb/ldad008 -
Journal of Clinical Medicine Jun 2023The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the... (Review)
Review
BACKGROUND
The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach.
METHODS
We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins. Eligible studies included animal studies that used BMP therapy and mesenchymal stem cells to promote bone regeneration in calvarial defects. Reviews, conference articles, book chapters, and non-English language studies were excluded. Two independent investigators conducted the search and data extraction.
RESULTS
Twenty-three studies published between 2010 and 2022 met our inclusion criteria after a full-text review of the forty-five records found in the search. Eight of the 23 studies used mice as models, while 15 used rats. The most common mesenchymal stem cell was bone marrow-derived, followed by adipose-derived. BMP-2 was the most popular. Stem cells were embedded in Scaffold (13), Transduction (7), and Transfection (3), and they were delivered BMP to cells. Each treatment used 2 × 10-1 × 10 mesenchymal stem cells, averaging 2.26 × 10. Most BMP-transduced MSC studies used lentivirus.
CONCLUSIONS
This systematic review examined BMP and MSC synergy in biomaterial scaffolds or alone. BMP therapy and mesenchymal stem cells in calvarial defects, alone, or with a scaffold regenerated bone. This method treats skull defects in clinical trials. The best scaffold material, therapeutic dosage, administration method, and long-term side effects need further study.
PubMed: 37373757
DOI: 10.3390/jcm12124064 -
Diagnostics (Basel, Switzerland) Aug 2022Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed... (Review)
Review
Sepsis is a series of life-threatening organ dysfunction caused by an impaired host response to infection. A large number of molecular studies of sepsis have revealed complex interactions between infectious agents and hosts that result in heterogeneous manifestations of sepsis. Sepsis can cause immunosuppression and increase the expression of checkpoint inhibitor molecules, including programmed death protein (PD-1) and programmed death ligand 1 (PD-L1), and thus PD-1 and PD-L1 are thought to be useful as diagnostic and prognostic tools for sepsis. PD-1 is an inhibitor of both adaptive and innate immune responses, and is expressed on activated T lymphocytes, natural killer (NK) cells, B lymphocytes, macrophages, dendritic cells (DCs), and monocytes, whereas PD-L1 is expressed on macrophages, some activated T and B cells, and mesenchymal stem cells as well as various non-hematopoietic cells. This systematic review aims to assess the PD-1 and PD-L1 protein expression levels and concentrations in septic and other infectious patients.
PubMed: 36010357
DOI: 10.3390/diagnostics12082004 -
International Journal of Molecular... Feb 2023Osteoarthritis remains an unfortunate long-term consequence of focal cartilage defects of the knee. Associated with functional loss and pain, it has necessitated the... (Meta-Analysis)
Meta-Analysis Review
Osteoarthritis remains an unfortunate long-term consequence of focal cartilage defects of the knee. Associated with functional loss and pain, it has necessitated the exploration of new therapies to regenerate cartilage before significant deterioration and subsequent joint replacement take place. Recent studies have investigated a multitude of mesenchymal stem cell (MSC) sources and polymer scaffold compositions. It is uncertain how different combinations affect the extent of integration of native and implant cartilage and the quality of new cartilage formed. Implants seeded with bone marrow-derived MSCs (BMSCs) have demonstrated promising results in restoring these defects, largely through in vitro and animal studies. A PRISMA systematic review and meta-analysis was conducted using five databases (PubMed, MEDLINE, EMBASE, Web of Science, and CINAHL) to identify studies using BMSC-seeded implants in animal models of focal cartilage defects of the knee. Quantitative results from the histological assessment of integration quality were extracted. Repair cartilage morphology and staining characteristics were also recorded. Meta-analysis demonstrated that high-quality integration was achieved, exceeding that of cell-free comparators and control groups. This was associated with repair tissue morphology and staining properties which resembled those of native cartilage. Subgroup analysis showed better integration outcomes for studies using poly-glycolic acid-based scaffolds. In conclusion, BMSC-seeded implants represent promising strategies for the advancement of focal cartilage defect repair. While a greater number of studies treating human patients is necessary to realize the full clinical potential of BMSC therapy, high-quality integration scores suggest that these implants could generate repair cartilage of substantial longevity.
Topics: Animals; Humans; Cartilage, Articular; Tissue Engineering; Bone Marrow; Cartilage Diseases; Tissue Scaffolds; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation
PubMed: 36834639
DOI: 10.3390/ijms24043227 -
Medicina (Kaunas, Lithuania) Mar 2023Cartilage regeneration using mesenchymal stem cells (MSCs) has been attempted to improve articular cartilage regeneration in varus knee osteoarthritis (OA) patients... (Review)
Review
Bone Marrow Aspirate Concentrate versus Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Combined Cartilage Regeneration Procedure in Patients Undergoing High Tibial Osteotomy: A Systematic Review and Meta-Analysis.
Cartilage regeneration using mesenchymal stem cells (MSCs) has been attempted to improve articular cartilage regeneration in varus knee osteoarthritis (OA) patients undergoing high tibial osteotomy (HTO). Bone marrow aspirate concentrate (BMAC) and human umbilical cord blood-derived MSCs (hUCB-MSCs) have been reported to be effective. However, whether BMAC is superior to hUCB-MSCs remains unclear. This systematic review and meta-analysis aimed to determine the clinical efficacy of cartilage repair procedures with BMAC or hUCB-MSCs in patients undergoing HTO. A systematic search was conducted using three global databases, PubMed, EMBASE, and the Cochrane Library, for studies in which the clinical outcomes after BMAC or hUCB-MSCs were used in patients undergoing HTO for varus knee OA. Data extraction, quality control, and meta-analysis were performed. To compare the clinical efficacy of BMAC and hUCB-MSCs, reported clinical outcome assessments and second-look arthroscopic findings were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). The present review included seven studies of 499 patients who received either BMAC (BMAC group, = 169) or hUCB-MSCs (hUCB-MSC group, = 330). Improved clinical outcomes were found in both BMAC and hUCB-MSC groups; however, a significant difference was not observed between procedures (International Knee Documentation Committee score; = 0.91, Western Ontario and McMaster Universities OA Index; = 0.05, Knee Society Score (KSS) Pain; = 0.85, KSS Function; = 0.37). On second-look arthroscopy, the hUCB-MSC group showed better International Cartilage Repair Society Cartilage Repair Assessment grade compared with the BMAC group ( < 0.001). Both BMAC and hUCB-MSCs with HTO improved clinical outcomes in varus knee OA patients, and there was no difference in clinical outcomes between them. However, hUCB-MSCs were more effective in articular cartilage regeneration than BMAC augmentation.
Topics: Humans; Osteoarthritis, Knee; Bone Marrow; Fetal Blood; Cartilage, Articular; Treatment Outcome; Mesenchymal Stem Cells; Osteotomy
PubMed: 36984635
DOI: 10.3390/medicina59030634 -
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 -
BMJ Open Nov 2022The purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The purpose of this meta-analysis was to investigate the efficacy and safety of mesenchymal stem cells (MSCs) combined with platelet-rich plasma (PRP) in the treatment of knee osteoarthritis (KOA).
DESIGN
Systematic review and meta-analysis.
PARTICIPANTS
Patients with KOA.
INTERVENTIONS
Use of MSCs+PRP.
PRIMARY AND SECONDARY OUTCOMES
Visual Analogue Scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS) and adverse reactions.
DATA SOURCES
PubMed, Cochrane Library, Embase and China National Knowledge Infrastructure were searched from inception to 15 July 2021.
MEASURES
The OR or weighted mean difference (WMD) of relevant outcome indicators was calculated. Study quality was evaluated using the risk-of-bias assessment tool version 2.0. Heterogeneity among studies was evaluated by calculating I. If I<50%, a fixed-effect model was applied; conversely, if I ≥50%, a random-effect model was applied.
RESULTS
Six controlled clinical trials with 493 cases were included. The meta-analysis results showed that in terms of the VAS score 3 months after treatment, MSCs+PRP had no significant effect on the reduction of the VAS score in patients with KOA compared with the control (p=0.09), hyaluronic acid (HA) (p=0.15) or PRP alone (p=0.07). MSCs+PRP was more effective in reducing the VAS score at 6 and 12 months after treatment than the control (WMD=-0.55, 95% CI -0.87 to -0.22, p<0.001), HA (WMD=-1.20, 95% CI -2.28 to -0.13, p=0.03) or PRP alone (WMD=-0.54, 95% CI -0.89 to -0.18, p=0.003). Regarding the decrease in the total WOMAC score at 3 and 6 months after treatment, MSCs+PRP showed better clinical efficacy than the control or HA alone (p<0.01). Compared with the control, MSCs+PRP exhibited no significant difference in reducing the total WOMAC score 12 months after treatment (p=0.39). There was no significant difference between MSCs+PRP and the control in terms of improvement of the KOOS 12 months after treatment (p=0.16). Compared with MSCs alone, MSCs+PRP exhibited no significant difference in the incidence of adverse reactions (p=0.22) 12 months after treatment.
CONCLUSIONS
Treatment with MSCs+PRP showed good clinical efficacy in improving pain and joint function in patients with KOA. Compared with MSCs alone, there was no significant difference in the incidence of adverse reactions with MSCs+PRP.
PROSPERO REGISTRATION NUMBER
CRD 42021275830.
Topics: Humans; Hyaluronic Acid; Injections, Intra-Articular; Mesenchymal Stem Cells; Osteoarthritis, Knee; Platelet-Rich Plasma; Randomized Controlled Trials as Topic
PubMed: 36385022
DOI: 10.1136/bmjopen-2022-061008 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2022Rhabdomyosarcoma (RMS) is a soft tissue malignant tumor of mesenchymal cell origin, which usually shows variable differentiation of muscle cells. It is the most common...
BACKGROUND
Rhabdomyosarcoma (RMS) is a soft tissue malignant tumor of mesenchymal cell origin, which usually shows variable differentiation of muscle cells. It is the most common solid sarcoma in children. The most usual site of occurrence are the head and neck regions. RMS presents a variety of histologic features, and so differential diagnosis with other small round cell tumors is needed. Hence, it has been very useful to the field to undertake additional immunohistochemical studies to determine the diagnosis and, on occasions, to assign subtype tumors.
MATERIAL AND METHODS
A systematic review of three databases (Medline, Biological Science Collection and Health & Medical Collection) was carried out with the purpose of analyzing rhabdomyosarcoma cases reported in the literature, specifically with localization in the head and neck regions in children. This strategy allowed us to identify the main anatomical site of appearance, the subtype of RMS, average age, histologic characteristics and immunohistochemistry markers used in a usual and any additional way.
RESULTS
According to the selection criteria in this systematic review, twelve articles, and fourteen cases were identified that highlight that the histological diagnosis usually presents cellular heterogeneity. Therefore, immunohistochemistry is needed to confirm the diagnosis.
CONCLUSIONS
Histologic characterization is not always sufficient for a conclusive diagnosis of RMS. Therefore, immunohistochemistry is helpful to determine the subtype and consequently, sometimes the behavior, treatment and prognosis. Additional markers may vary according to the institution and the need of particular cases.
Topics: Child; Humans; Rhabdomyosarcoma; Immunohistochemistry; Prognosis; Diagnosis, Differential
PubMed: 36173721
DOI: 10.4317/medoral.25508 -
Medicina (Kaunas, Lithuania) Jan 2023Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic... (Review)
Review
Efficacy of Adipose-Derived Mesenchymal Stem Cells and Stromal Vascular Fraction Alone and Combined to Biomaterials in Tendinopathy or Tendon Injury: Systematic Review of Current Concepts.
Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is often suboptimal and impaired. This is due to the inherent scarce ability of tendon tissue to repair and return itself to the original structure. Recently, Adipose-derived mesenchymal stem cells (ADSC) and stromal vascular fraction (SVF) have gained a central interest in the scientific community, demonstrating their effectiveness in treatments of acute and chronic tendon disorders in animals and humans. Either enzymatic or mechanical procedures to obtain ADSC and SVF have been described and used in current clinical practice. However, no unified protocols and processes have been established. This systematic review aims at providing a comprehensive update of the literature on the clinical application of ADSC enzymatically or mechanically processed to obtain SVF, alone and in association with biomaterials in the local treatment of tendinopathy and tendon injury in vivo, in animal models and humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Thirty-two articles met our inclusion criteria, with a total of 18 studies in animals, 10 studies in humans and 4 studies concerning the application of biomaterials in vivo in animals. The review of the literature suggests that ADSC/SVF therapy can represent a promising alternative in tendonregenerative medicine for the enhancement of tendon healing. Nevertheless, further investigations and randomized control trials are needed to improve the knowledge, standardize the procedures and extend the consensus on their use for such applications.
Topics: Animals; Humans; Stromal Vascular Fraction; Biocompatible Materials; Mesenchymal Stem Cells; Tendinopathy; Tendons
PubMed: 36837474
DOI: 10.3390/medicina59020273 -
The application and progress of stem cells in auricular cartilage regeneration: a systematic review.Frontiers in Cell and Developmental... 2023The treatment of microtia or acquired ear deformities by surgery is a significant challenge for plastic and ENT surgeons; one of the most difficult points is... (Review)
Review
The treatment of microtia or acquired ear deformities by surgery is a significant challenge for plastic and ENT surgeons; one of the most difficult points is constructing the scaffold for auricular reconstruction. As a type of cell with multiple differentiation potentials, stem cells play an essential role in the construction of cartilage scaffolds, and therefore have received widespread attention in ear reconstructive research. A literature search was conducted for peer-reviewed articles between 2005 and 2023 with the following keywords: stem cells; auricular cartilage; ear cartilage; conchal cartilage; auricular reconstruction, regeneration, and reparation of chondrocytes; tissue engineering in the following databases: PubMed, MEDLINE, Cochrane, and Ovid. Thirty-three research articles were finally selected and their main characteristics were summarized. Adipose-derived stem cells (ADSCs), bone marrow mesenchymal stem cells (BMMSCs), perichondrial stem/progenitor cells (PPCs), and cartilage stem/progenitor cells (CSPCs) were mainly used in chondrocyte regeneration. Injecting the stem cells into the cartilage niche directly, co-culturing the stem cells with the auricular cartilage cells, and inducing the cells in the chondrogenic medium were the main methods that have been demonstrated in the studies. The chondrogenic ability of these cells was observed , and they also maintained good elasticity and morphology after implantation for a period of time. ADSC, BMMSC, PPC, and CSPC were the main stem cells that have been researched in craniofacial cartilage reconstruction, the regenerative cartilage performed highly similar to normal cartilage, and the test of AGA and type II collagen content also proved the cartilage property of the neo-cartilage. However, stem cell reconstruction of the auricle is still in the initial stage of animal experiments, transplantation with such scaffolds in large animals is still lacking, and there is still a long way to go.
PubMed: 37564374
DOI: 10.3389/fcell.2023.1204050