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Bone Reports Jun 2024Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast... (Review)
Review
INTRODUCTION
Tumor-induced osteomalacia (TIO), is a rare acquired paraneoplastic syndrome characterized by defective bone mineralization, caused by the overproduction of fibroblast growth factor 23 (FGF23) by a tumor.
MATERIAL AND METHODS
We conducted a systematic review to identify all case reports of TIO, focusing on those associated with mesenchymal tumors. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) consensus, and we included patients with a diagnosis of TIO and histological confirmation of phosphaturic mesenchymal tumors or resolution of the condition after treatment of the tumor. Bibliographical searches were carried out until December 2023 in the Cochrane Library, Medline and Embase, as well as congress abstracts online.
RESULTS
We identified 769 articles with 1979 cases reported. Most patients were adults, with a higher incidence on men. Disease duration before diagnosis is a mean of 4.8 years. Most tumors were histologically classified as PMT. Lower limbs were the predominant location. Hypophosphatemia was present in 99.8 % of patients. The FGF23 was elevated at diagnosis in 95.5 %. Resection of the tumor was the treatment of choice in most of patients. After resection, there was a clinical improvement in 97.6 % of cases, and serum phosphorus and FGF23 levels returned to normal ranges in 91.5 % and 81.4 % of the patients, respectively.
CONCLUSION
TIO is usually misdiagnosed with rheumatological or musculoskeletal disorders. The diagnosis should be suspected in patients with hypophosphatemic osteomalacia, and the measurement of serum FGF23 can be useful for diagnosis and management.
PubMed: 38774264
DOI: 10.1016/j.bonr.2024.101772 -
Clinical and Experimental Medicine Nov 2023Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for... (Meta-Analysis)
Meta-Analysis
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355; P < 0.001) and miR-34a-5p (logOR 6.955; P < 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586; P < 0.001) and miR-140-5p (logOR 6.373; P < 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-β were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA.
Topics: Humans; MicroRNAs; Osteoarthritis; Biomarkers
PubMed: 37027064
DOI: 10.1007/s10238-023-01063-8 -
Stem Cell Research & Therapy Oct 2023Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell... (Meta-Analysis)
Meta-Analysis Review
AIM
Although the efficacy and safety of mesenchymal stem cell therapy for liver cirrhosis have been demonstrated in several studies. Clinical cases of mesenchymal stem cell therapy for patients with liver cirrhosis are limited and these studies lack the consistency of treatment effects. This article aimed to systematically investigate the efficacy and safety of mesenchymal stem cells in the treatment of liver cirrhosis.
METHOD
The data source included PubMed/Medline, Web of Science, EMBASE, and Cochrane Library, from inception to May 2023. Literature was screened by the PICOS principle, followed by literature quality evaluation to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Outcome indicators of the assessment included liver functions and adverse events. Statistical analysis was performed using Review Manager 5.4.
RESULTS
A total of 11 clinical trials met the selection criteria. The pooled analysis' findings demonstrated that both primary and secondary indicators had improved. Compared to the control group, infusion of mesenchymal stem cells significantly increased ALB levels in 2 weeks, 1 month, 3 months, and 6 months, and significantly decreased MELD score in 1 month, 2 months, and 6 months, according to a subgroup analysis using a random-effects model. Additionally, the hepatic arterial injection favored improvements in MELD score and ALB levels. Importantly, none of the included studies indicated any severe adverse effects.
CONCLUSION
The results showed that mesenchymal stem cell was effective and safe in the treatment of liver cirrhosis, improving liver function (such as a decrease in MELD score and an increase in ALB levels) in patients with liver cirrhosis and exerting protective effects on complications of liver cirrhosis and the incidence of hepatocellular carcinoma. Although the results of the subgroup analysis were informative for the selection of mesenchymal stem cells for clinical treatment, a large number of high-quality randomized controlled trials validations are still needed.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Liver Cirrhosis; Carcinoma, Hepatocellular; Liver Neoplasms
PubMed: 37864199
DOI: 10.1186/s13287-023-03518-x -
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 -
Pharmacology & Therapeutics Jan 2024The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not... (Review)
Review
The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach.
Topics: Animals; Connective Tissue Growth Factor; Fibrosis; Fibroblasts; Transforming Growth Factor beta; Idiopathic Pulmonary Fibrosis; Transforming Growth Factor beta1; Lung
PubMed: 38103794
DOI: 10.1016/j.pharmthera.2023.108578 -
International Journal of Molecular... Jul 2023Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and... (Review)
Review
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as "spinal cord injury," "stem cells," "stem cell therapy," "mesenchymal stem cells," and "traumatic spinal cord injury". Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Spinal Cord Injuries; Cell- and Tissue-Based Therapy; Myelin Sheath; Mesenchymal Stem Cells; Spinal Cord
PubMed: 37511478
DOI: 10.3390/ijms241411719 -
Regenerative Therapy Dec 2023The incidence of hair loss (HL) and telogen effluvium (TE) in COVID-19 patients has been reported in several studies.
BACKGROUND
The incidence of hair loss (HL) and telogen effluvium (TE) in COVID-19 patients has been reported in several studies.
OBJECTIVES
Evaluate both the increased incidence of HL and TE in COVID-19 and the effectiveness of Platelet-Rich Plasma (PRP), Adipose-derived Mesenchymal Stem Cells (AD-MSCs), and Human Follicle Stem Cells (HFSCs) in these patients.
METHODS
The protocol was developed by the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of PubMed, MEDLINE, Embase, Clinicaltrials. gov, Scopus, and Cochrane databases has been performed to identify papers focusing on HL and TE COVID-19 related, and papers focusing on AD-MSCs, HFSC, and PRP use.
RESULTS
Of the 404 articles initially identified focusing on HL and TE, 44 were related to COVID-19, and finally, only 6 were analyzed. On the other way, 331 articles focusing on AD-MSCs, HFSC, and PRP were initially identified. Of these, only 6 articles PRP (n = 3), AD-MSCs, and HFSCs (n = 3) have been analyzed.
CONCLUSION
Collected data confirmed both an increased incidence of HL and TE in COVID-19 patients, preliminarily, the related effectiveness of AD-MSCs, HFSCs, and PRP without major side effects.
PubMed: 37519906
DOI: 10.1016/j.reth.2023.07.001 -
The Cochrane Database of Systematic... Nov 2023Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute... (Review)
Review
BACKGROUND
Perinatal stroke refers to a diverse but specific group of cerebrovascular diseases that occur between 20 weeks of fetal life and 28 days of postnatal life. Acute treatment options for perinatal stroke are limited supportive care, such as controlling hypoglycemia and seizures. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. Preclinical findings have culminated in ongoing human neonatal studies.
OBJECTIVES
To evaluate the benefits and harms of stem cell-based interventions for the treatment of stroke in newborn infants compared to control (placebo or no treatment) or stem-cell based interventions of a different type or source.
SEARCH METHODS
We searched CENTRAL, PubMed, Embase, and three trials registries in February 2023. We planned to search the reference lists of included studies and relevant systematic reviews for studies not identified by the database searches.
SELECTION CRITERIA
We attempted to include randomized controlled trials, quasi-randomized controlled trials, and cluster trials that evaluated any of the following comparisons. • Stem cell-based interventions (any type) versus control (placebo or no treatment) • Mesenchymal stem/stromal cells (MSCs) of a specifictype (e.g. number of doses or passages) or source (e.g. autologous/allogeneic or bone marrow/cord) versus MSCs of another type or source • Stem cell-based interventions (other than MSCs) of a specific type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, or induced pluripotent stem cell-derived cells) or source (e.g. autologous/allogeneic or bone marrow/cord) versus stem cell-based interventions (other than MSCs) of another type or source • MSCs versus stem cell-based interventions other than MSCs We planned to include all types of transplantation regardless of cell source (bone marrow, cord blood, Wharton's jelly, placenta, adipose tissue, peripheral blood), type of graft (autologous or allogeneic), and dose.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were all-cause neonatal mortality, major neurodevelopmental disability, and immune rejection or any serious adverse event. Our secondary outcomes included all-cause mortality prior to first hospital discharge, seizures, adverse effects, and death or major neurodevelopmental disability at 18 to 24 months of age. We planned to use GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified no completed or ongoing randomized trials that met our inclusion criteria. We excluded three studies: two were phase 1 trials, and one included newborn infants with conditions other than stroke (i.e. cerebral ischemia and anemia). Among the three excluded studies, we identified the first phase 1 trial on the use of stem cells for neonatal stroke. It reported that a single intranasal application of bone marrow-derived MSCs in term neonates with a diagnosis of perinatal arterial ischemic stroke (PAIS) was feasible and apparently not associated with severe adverse events. However, the trial included only 10 infants, and follow-up was limited to three months.
AUTHORS' CONCLUSIONS
No evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment of stroke in newborn infants. We identified no ongoing studies. Future clinical trials should focus on standardizing the timing and method of cell delivery and cell processing to optimize the therapeutic potential of stem cell-based interventions and safety profiles. Phase 1 and large animal studies might provide the groundwork for future randomized trials. Outcome measures should include all-cause mortality, major neurodevelopmental disability and immune rejection, and any other serious adverse events.
Topics: Infant, Newborn; Pregnancy; Female; Infant; Humans; Infant Mortality; Stem Cell Transplantation; Stroke; Seizures
PubMed: 37994736
DOI: 10.1002/14651858.CD015582.pub2 -
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 -
Child's Nervous System : ChNS :... May 2024Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignant tumor in pediatric population. IMC can present as extra- or intra-axial lesion in pediatric patients,... (Review)
Review
BACKGROUND
Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignant tumor in pediatric population. IMC can present as extra- or intra-axial lesion in pediatric patients, though the former is commoner causing raised intracranial pressure (ICP). Radiological diagnosis is a challenge in these cases, as is it difficult to differentiate these from other extra-axial neoplasms due to the wide differential diagnosis in pediatric population. We aim to systematically review the literature and present a rare case of extraskeletal intracranial mesenchymal chondrosarcoma treated with safe maximal resection.
METHODS
A systematic review of literature was conducted in accordance with PRISMA guidelines. PubMed and Scopus databases were queried using the search terms, "primary intracranial chondrosarcoma", "extraskeletal mesenchymal chondrosarcoma", "mesenchymal chondrosarcoma" and "pediatric". Presentation, surgical management and outcome of a 15-year-old male with an extraskeletal IMC are also described.
RESULTS
The search yielded 25 articles which met the inclusion criteria. These published records consisted of 33 IMC cases with mean age at presentation of 9.81 ± 5.2 years (range 2 months to 18 years). Frontal region was the commonest locations (11, 33.3%). Most common presentation was headache (14, 42.4%). All patients underwent surgical intervention: gross total resection (20, 60.6%), subtotal resection (9, 27.3%) and no extent mentioned (4, 12.1%). No adjuvant therapy was received in 15 patients (45.5%). On latest follow-up, 11 patients (33.3%) are on remission, 5 patients (15.2%) are symptom free, 3 patients (9.1%) had recurrence, 2 patients (6.1%) had metastasis and 9 patients (27.3%) expired.
CONCLUSION
IMC is a rare entity in pediatric population with imaging findings which are non-characteristic leading to its diagnostic challenge. It can masquerade as other extra-axial intracranial neoplasm (meningioma or hemangiopericytoma). Combination of clinico-radiological and pathological examination can help in accurate diagnosis. Safe Maximal resection followed by radiotherapy is the preferred treatment strategy.
PubMed: 38762839
DOI: 10.1007/s00381-024-06452-2