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The Cochrane Database of Systematic... May 2022Crohn's disease (CD) is an inflammatory bowel disease that causes inflammation and stricture, of any part of the mucosa and the gut wall. It forms skip lesions, sparing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Crohn's disease (CD) is an inflammatory bowel disease that causes inflammation and stricture, of any part of the mucosa and the gut wall. It forms skip lesions, sparing the areas in between the affected parts of the gastrointestinal tract. Crohn's disease could have one of three complications; fistula, intestinal obstruction due to stricture, or gastrointestinal inflammation presenting as severe diarrhoea. Stem cell therapy (SCT) is an innovative treatment that has been recently used in CD. The exact role of SCT in CD is still unclear. Stem cells modify the immunity of the patients or act as a "reset tool" for the immune system as in the case of systemically-injected stem cells, or regenerate the affected area of necrotic and inflammatory tissue as in the case of local injection into the lesion. Stem cells are a wide variety of cells including pluripotent stem cells or differentiated stem cells. The hazards range from rejection to symptomatic manifestations as fever or increase infection. OBJECTIVES: The objective of this Cochrane systematic review is to assess the effects of stem cell transplantation compared to standard of care alone or with placebo on efficacy and safety outcomes in patients with refractory CD.
SEARCH METHODS
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and clinical trial registries (Clinicaltrials.gov, World Health Organization-International Clinical Trials Registry Platform WHO ICTRP) from inception to 19 March 2021, without any language, publication year, or publication status restrictions. In addition, we searched references of included studies and review articles for further references. An update of the published studies was done during the writing of the review.
SELECTION CRITERIA
We included only randomised controlled trials (RCTs) that assessed the effectiveness and safety of SCT in refractory CD versus standard care alone (control) or with placebo.
DATA COLLECTION AND ANALYSIS
Two review authors (SEN and SFA) independently screened the studies retrieved from the search results for inclusion, extracted data and assessed the risk of bias. Any disagreement was resolved through a consensus between the authors. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We conducted our search on 19 March 2021 and identified 639 records. We added two records by a manual search of the published reviews on the topic to a total of 641 records. The Covidence program removed 125 duplicates making a total of 516 reports. Two review authors (SEN and SFA) screened titles and abstracts and excluded 451 records with the remaining 65 for full-text records screened independently by the two authors; only 18 studies were considered for inclusion. We included seven RCTs with a total of 442 participants for the meta-analysis. The intervention group included 234 patients, and the control group included 208 patients. Nine trials are ongoing and, two abstracts are awaiting classification. All patients in the control and intervention groups received the standard therapy for CD. Only three studies used blinding methods for the control group in the form of a placebo, with one study of the three stated that the blinding method was inefficient. The patients and personnel were aware of the intervention in the rest of the four studies as they were open-label trials. However, the effect of unblinding was balanced by the low risk of detection bias in five of the included studies. The evidence is uncertain about the effect of SCT on achieving clinical remission as compared to control/placebo (risk ratio (RR) 1.88, 95% Confidence Interval (CI) 0.80 to 4.41; 3 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT on achieving Crohn's Disease Activity Index (CDAI) <150 at 24 weeks compared to control (RR1.02 95% CI 0.67 to 1.56; 4 studies; very-low certainty evidence). SCT is likely to achieve fistula closure as compared to the control/placebo both in the short term (RR 1.48, 95% CI 1.12 to 1.96); low-certainty evidence) and in the long term (RR 1.42, 95% CI 1.09 to 1.87; 4 studies; low-certainty evidence) follow-up. The evidence is very uncertain about the effect of SCT to cause no difference in the number of total adverse events as compared to the control/placebo (RR 0.99, 95% CI [0.88 to 1.13); 4 studies; very-low-certainty evidence). However, SCT is likely to increase the number of serious adverse events as compared to the control/placebo (RR 1.22, 95% CI 0.88 to 1.67; 7 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT to decrease the withdrawal due to adverse events as compared to the control/placebo (RR 0.78, 95% CI 0.32 to 1.89; 3 studies; very-low certainty evidence). Funding by pharmaceutical companies was found in three studies, with one including more than 50% of our studied population.
AUTHORS' CONCLUSIONS
SCT shows an uncertain effect on clinical remission with low certainty of evidence. SCT shows an uncertain effect on CDAI score to reach <150 after 24 weeks of treatment, with very low certainty evidence. SCT shows beneficial effects on fistula-closure during short and long-term follow-up with low-certainty evidence in both outcomes. There was no change in the total number of adverse events with SCT as compared to control, with very low certainty evidence. While there was a moderate effect on increasing the number of serious adverse events in the SCT group, as compared to the control with low-certainty evidence. Withdrawal due to adverse events was slightly higher in the control group with very low certainty evidence. All the participants were refractory to standard medical treatment, but the number of participants was small, this may limit the generalizability of the results. Further research is needed for validation. More objective outcomes are needed in the assessment of stem cell effectiveness in the treatment of Crohn's disease, especially the intestinal CD subtype; with standardization of the dose, methods of stem cell preparation, route of administration, and inclusion criteria to the studies to achieve clear results.
Topics: Constriction, Pathologic; Crohn Disease; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; Remission Induction
PubMed: 35556242
DOI: 10.1002/14651858.CD013070.pub2 -
BioMed Research International 2021The SARS-CoV-2 virus is the cause of the latest pandemic of the 21st century; it is responsible for the development of COVID-19. Within the multiple study models for...
BACKGROUND
The SARS-CoV-2 virus is the cause of the latest pandemic of the 21st century; it is responsible for the development of COVID-19. Within the multiple study models for both the biology and the treatment of SARS-CoV-2, the use of stem cells has been proposed because of their ability to increase the immune response and to repair tissue. Therefore, the objective of this review is to evaluate the role of stem cells against SARS-CoV-2 and COVID-19 in order to identify their potential as a study model and as a possible therapeutic source against tissue damage caused by this virus. Therefore, the following research question was established: What is the role of stem cells in the study of SARS-CoV-2 and the treatment of COVID-19?
MATERIALS AND METHODS
A search was carried out in the electronic databases of PUBMED, Scopus, and ScienceDirect. The following keywords were used: "SARS-CoV-2," "COVID-19," and "STEM CELL," plus independent search strategies with the Boolean operators "OR" and "AND." The identified reports were those whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19. For the development of this study, the following inclusion criteria were taken into account: studies whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19 and clinical case studies, case reports, clinical trials, pilot studies, in vitro, or in vivo studies. For assessment of the risk of bias for in vitro studies, the SciRAP tool was used. The data collected for each type of study, clinical or in vitro, were analyzed with descriptive statistics using the SPSS V.22 program.
RESULTS
Of the total of studies included ( = 39), 22 corresponded to in vitro investigations and 17 to human studies (clinical cases ( = 9), case series ( = 2), pilot clinical trials ( = 5), clinical trials ( = 1)). In vitro studies that induced pluripotent stem cells were the most used ( = 12), and in clinical studies, the umbilical stem cells derived were the most reported ( = 11). The mean age of the study subjects was 58.3 years. After the application of stem cell therapy, the follow-up period was 8 days minimum and 90 days maximum. . The mechanism by which the virus enters the cell is through protein "S," located on the surface of the membrane, by recognizing the ACE2 receptor located on the target cell. The evidence that the expression of ACE2 and TMPRSS2 in stem cells indicates that stem cells from bone marrow and amniotic fluid have very little expression. This shows that stem cell has a low risk of infection with SARS-CoV-2.
CONCLUSION
The use of stem cells is a highly relevant therapeutic option. It has been shown in both in vitro studies and clinical trials that it counteracts the excessive secretion of cytokines. There are even more studies that focus on long-term follow-up; thus, the potential for major side effects can be analyzed more clearly. Finally, the ethical use of stem cells from fetal or infant origin needs to be regulated. The study was registered in PROSPERO (no. CRD42021229038). The limitations of the study were because of the methodology employed, the sample was not very large, and the follow-up period of the clinical studies was relatively short.
Topics: COVID-19; Clinical Trials as Topic; Humans; SARS-CoV-2; Stem Cell Transplantation; Stem Cells
PubMed: 34458372
DOI: 10.1155/2021/9915927 -
Frontiers in Cellular Neuroscience 2021The brain is our most complex and least understood organ. Animal models have long been the most versatile tools available to dissect brain form and function; however,...
The brain is our most complex and least understood organ. Animal models have long been the most versatile tools available to dissect brain form and function; however, the human brain is highly distinct from that of standard model organisms. In addition to existing models, access to human brain cells and tissues is essential to reach new frontiers in our understanding of the human brain and how to intervene therapeutically in the face of disease or injury. In this review, we discuss current and developing culture models of human neural tissue, outlining advantages over animal models and key challenges that remain to be overcome. Our principal focus is on advances in engineering neural cells and tissue constructs from human pluripotent stem cells (PSCs), though primary human cell and slice culture are also discussed. By highlighting studies that combine animal models and human neural cell culture techniques, we endeavor to demonstrate that clever use of these orthogonal model systems produces more reproducible, physiological, and clinically relevant data than either approach alone. We provide examples across a range of topics in neuroscience research including brain development, injury, and cancer, neurodegenerative diseases, and psychiatric conditions. Finally, as testing of PSC-derived neurons for cell replacement therapy progresses, we touch on the advancements that are needed to make this a clinical mainstay.
PubMed: 34867204
DOI: 10.3389/fncel.2021.767457 -
Odontology Jan 2023The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in the regeneration of periodontal bone defects in animal models. A systematic review... (Meta-Analysis)
Meta-Analysis
The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in the regeneration of periodontal bone defects in animal models. A systematic review and meta-analysis were conducted following the PRISMA guidelines, and the study was recorded in PROSPERO under reference number CDR42021247462. The PICO question was: is periodontal regeneration (cementum, periodontal ligament and alveolar bone) with MSCs more effective than other techniques? Three groups were considered: Group 1: MSCs alone or mixed with regenerative materials. Group 2: only regenerative materials. Group 3: no regenerative material nor MSCs. The search was conducted using MeSH with a total of 18 articles for qualitative analysis and 5 for quantitative analysis. For the meta-analysis, a modification of the effect size algorithm was developed, which considered a comparison of means between treatments using the Student's t sample distribution. When comparing the effect size between Group 1 and Group 2, the effect size for the new cementum was 2.83 mm with an estimated confidence interval of 95% (CI 95%) between 0.48 and 5.17 mm. When considering the fit to a random-effects model, the combined variance (τ) was 6.1573 mm, with a standard deviation (SD) of 5.6008 mm and a percentage of total heterogeneity I of 92.33% (p < 0.0001). For new bone, the effect size was 0.88 mm, CI 95% - 0.25 to 2.01 mm, τ = 1.3108 mm (SD = 1.2021 mm) and I = 80.46%, p = 0.0004). With regard to the new periodontal ligament, it was not possible for the meta-analysis to be performed. MSCs have a greater capacity for tissue regeneration in root cementum than in alveolar bone compared to other regenerative materials.
Topics: Animals; Alveolar Bone Loss; Bone Regeneration; Guided Tissue Regeneration, Periodontal; Models, Animal; Periodontal Ligament; Mesenchymal Stem Cells
PubMed: 35788845
DOI: 10.1007/s10266-022-00725-5 -
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 -
Cureus Sep 2019Objective The effects of stem cell therapy in patients with advanced heart failure is an ongoing debate. This study aimed to assess the effectiveness and safety of stem...
Objective The effects of stem cell therapy in patients with advanced heart failure is an ongoing debate. This study aimed to assess the effectiveness and safety of stem cell therapy plus the standard of care as compared to the placebo plus the standard of care in advanced heart failure patients. Methods A comprehensive keyword search of PubMed between 2017 and 2019 was performed to extract trials conducted with stem cell therapy controlled with placebo in advanced heart failure. We included randomized controlled trials (RCTs) with data on safety and efficacy in patients with advanced heart failure after stem cell transplantation. Results Six RCTs, consisting of 569 patients, were selected. Three-hundred sixty-seven (367) out of 369 participants from the eligible four out of six RCTs were included for efficacy analysis, as we lost two patients from the final analysis due to early death. Five-hundred twenty-six (526) out of 527 participants from the eligible five out of six RCTs were included for safety analysis, as we lost one patient from the final analysis for not being able to receive the intervention. Stem cell transplantation significantly improved left ventricular ejection fraction (LVEF) by 4.58% (95% CI: 3.73-5.43%; p = 0.00001), improved left ventricular end-systolic volume (LVESV) by -5.18 ml (95% CI: -9.74 to -0.63 ml; p =0.03), and there was no difference in the risk of all-cause mortality (OR 0.97; 95% CI: 0.52 to 1.78%; p = 0.91). The above results correlate with the previous meta-analysis data conducted in 2016. Conclusions This meta-analysis provided the cumulative efficacy and safety results of stem cell transplantation in advanced heart failure based on recent RCTs. The above results suggest that stem cell therapy was associated with a moderate improvement in LVEF, and the safety analysis indicates no increased risk of mortality in patients with advanced heart failure. This meta-analysis recommends conducting more RCTs comparing stem cell transplantation and placebo with a larger patient population and longer follow-up.
PubMed: 31696004
DOI: 10.7759/cureus.5585 -
Stem Cells (Dayton, Ohio) Oct 2022The TP53 gene is unarguably one of the most studied human genes. Its encoded protein, p53, is a tumor suppressor and is often called the "guardian of the genome" due to...
The TP53 gene is unarguably one of the most studied human genes. Its encoded protein, p53, is a tumor suppressor and is often called the "guardian of the genome" due to its pivotal role in maintaining genome stability. Historically, most studies of p53 have focused on its roles in somatic cells and tissues, but in the last 2 decades, its functions in embryonic stem cells (ESCs) and induced pluripotent stem cells have attracted increasing attention. Recent studies have identified p53 as a critical regulator of pluripotency, self-renewal, differentiation, proliferation, and genome stability in mouse and human embryonic stem cells. In this article, we systematically review the studies on the functions of p53 in ESCs, provide an updated overview, attempt to reconcile controversial results described in the literature, and discuss the relevance of these cellular functions of p53 to its roles in tumor suppression.
Topics: Animals; Humans; Mice; Cell Differentiation; Embryonic Stem Cells; Genes, p53; Genomic Instability; Tumor Suppressor Protein p53
PubMed: 35904997
DOI: 10.1093/stmcls/sxac051 -
Frontiers in Behavioral Neuroscience 2024Neurexins, essential synaptic proteins, are linked to neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD) and schizophrenia.
BACKGROUND
Neurexins, essential synaptic proteins, are linked to neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD) and schizophrenia.
OBJECTIVE
Through this systematic review, we aimed to shed light on the relationship between neurexin dysfunction and its implications in neurodevelopmental and neuropsychiatric manifestations. Both animal and human-induced pluripotent stem cell (hiPSC) models served as our primary investigative platforms.
METHODS
Utilizing the PRISMA 2020 guidelines, our search strategy involved scouring articles from the PubMed and Google Scholar databases covering a span of two decades (2003-2023). Of the initial collection, 27 rigorously evaluated studies formed the essence of our review.
RESULTS
Our review suggested the significant ties between neurexin anomalies and neurodevelopmental and neuropsychiatric outcomes, most notably ASD. Rodent-based investigations delineated pronounced ASD-associated behaviors, and hiPSC models derived from ASD-diagnosed patients revealed the disruptions in calcium dynamics and synaptic activities. Additionally, our review underlined the integral role of specific neurexin variants, primarily NRXN1, in the pathology of schizophrenia. It was also evident from our observation that neurexin malfunctions were implicated in a broader array of these disorders, including ADHD, intellectual challenges, and seizure disorders.
CONCLUSION
This review accentuates the cardinal role neurexins play in the pathological process of neurodevelopmental and neuropsychiatric disorders. The findings underscore a critical need for standardized methodologies in developing animal and hiPSC models for future studies, aiming to minimize heterogeneity. Moreover, we highlight the need to expand research into less studied neurexin variants (i.e., NRXN2 and NRXN3), broadening the scope of our understanding in this field. Our observation also projects hiPSC models as potent tools for bridging research gaps, promoting translational research, and fostering the development of patient-specific therapeutic interventions.
PubMed: 38380150
DOI: 10.3389/fnbeh.2024.1297374 -
PloS One 2024Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial...
BACKGROUND
Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), has played a pivotal role in refining iPSC classification, monitoring cell functionality, and conducting genetic analysis. These enhancements are broadening the applications of iPSC technology in disease modelling, drug screening, and regenerative medicine. This review aims to explore the role of AI in the advancement of iPSC research.
METHODS
In December 2023, data were collected from three electronic databases (PubMed, Web of Science, and Science Direct) to investigate the application of AI technology in iPSC processing.
RESULTS
This systematic scoping review encompassed 79 studies that met the inclusion criteria. The number of research studies in this area has increased over time, with the United States emerging as a leading contributor in this field. AI technologies have been diversely applied in iPSC technology, encompassing the classification of cell types, assessment of disease-specific phenotypes in iPSC-derived cells, and the facilitation of drug screening using iPSC. The precision of AI methodologies has improved significantly in recent years, creating a foundation for future advancements in iPSC-based technologies.
CONCLUSIONS
Our review offers insights into the role of AI in regenerative and personalized medicine, highlighting both challenges and opportunities. Although still in its early stages, AI technologies show significant promise in advancing our understanding of disease progression and development, paving the way for future clinical applications.
Topics: Induced Pluripotent Stem Cells; Humans; Artificial Intelligence; Regenerative Medicine; Machine Learning
PubMed: 38771829
DOI: 10.1371/journal.pone.0302537 -
Advanced Drug Delivery Reviews 2020Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human...
Modeling of human organs has long been a task for scientists in order to lower the costs of therapeutic development and understand the pathological onset of human disease. For decades, despite marked differences in genetics and etiology, animal models remained the norm for drug discovery and disease modeling. Innovative biofabrication techniques have facilitated the development of organ-on-a-chip technology that has great potential to complement conventional animal models. However, human organ as a whole, more specifically the human heart, is difficult to regenerate in vitro, in terms of its chamber specific orientation and its electrical functional complexity. Recent progress with the development of induced pluripotent stem cell differentiation protocols, made recapitulating the complexity of the human heart possible through the generation of cells representative of atrial & ventricular tissue, the sinoatrial node, atrioventricular node and Purkinje fibers. Current heart-on-a-chip approaches incorporate biological, electrical, mechanical, and topographical cues to facilitate tissue maturation, therefore improving the predictive power for the chamber-specific therapeutic effects targeting adult human. In this review, we will give a summary of current advances in heart-on-a-chip technology and provide a comprehensive outlook on the challenges involved in the development of human physiologically relevant heart-on-a-chip.
Topics: Drug Discovery; Heart; Humans; Induced Pluripotent Stem Cells; Lab-On-A-Chip Devices; Microtechnology; Myocytes, Cardiac; Tissue Engineering
PubMed: 31917972
DOI: 10.1016/j.addr.2019.12.002