-
F1000Research 2022Retinoic acid plays an essential role in testicular development and functions, especially spermatogenesis. We have reviewed the role of retinoic acid from basic...
Retinoic acid plays an essential role in testicular development and functions, especially spermatogenesis. We have reviewed the role of retinoic acid from basic (molecular) to clinical application. A search was conducted in the online database including PubMed, Google Scholar, and Scopus for English studies published in the last eight years about this issue. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in assessing the studies we are going to investigate. Studies indicated that retinoic acid plays an essential role during pluripotent stem cell migration and lineage commitment, cell differentiation, apoptosis, stem cell number regulation, and maturation arrest in spermatogenic cells. Retinoic acid can also affect related protein expression and signaling pathways at different stages of spermatogenesis. Four studies have applied retinoic acid to humans, all of them in the single-arm observational study. The results look promising but need further research with more controlled study methods, randomization, and large samples. This current systematic review emphasizes a novel retinoic acid mechanism that has not been well described in the literature previously on its functions during the first seven days of spermatogenesis, leading to new directions or explanations of male infertility cause and treatments as a part of reproductive health care.
Topics: Germ Cells; Humans; Infertility, Male; Male; Observational Studies as Topic; Spermatogenesis; Spermatozoa; Tretinoin
PubMed: 35967975
DOI: 10.12688/f1000research.110510.2 -
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 -
Stem Cell Research & Therapy Jul 2022Organoids are 3D structures grown from pluripotent stem cells derived from human tissue and serve as in vitro miniature models of human organs. Organoids are expected to... (Review)
Review
Organoids are 3D structures grown from pluripotent stem cells derived from human tissue and serve as in vitro miniature models of human organs. Organoids are expected to revolutionize biomedical research and clinical care. However, organoids are not seen as morally neutral. For instance, tissue donors may perceive enduring personal connections with their organoids, setting higher bars for informed consent and patient participation. Also, several organoid sub-types, e.g., brain organoids and human-animal chimeric organoids, have raised controversy. This systematic review provides an overview of ethical discussions as conducted in the scientific literature on organoids. The review covers both research and clinical applications of organoid technology and discusses the topics informed consent, commercialization, personalized medicine, transplantation, brain organoids, chimeras, and gastruloids. It shows that further ethical research is needed especially on organoid transplantation, to help ensure the responsible development and clinical implementation of this technology in this field.
Topics: Animals; Biomedical Research; Brain; Humans; Organoids; Pluripotent Stem Cells; Precision Medicine
PubMed: 35870991
DOI: 10.1186/s13287-022-02950-9 -
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 -
Cureus May 2022Somatic () mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).... (Review)
Review
A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With Inherited Bone Marrow Failure Syndromes.
Somatic () mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Mono-allelic mutations in germline cells may cause familial platelet disorder (FPD), an inherited bone marrow failure syndrome (IBMFS) associated with an increased lifetime risk of AML. It is suspected that additional mutations may play a role in the pathogenesis of hematological malignancies in IBMFS. This review aims to study the role of mutations in the pathogenesis of hematological malignancies in patients with IBMFS. A PubMed database search was conducted using the following medical subject heading (MeSH) terms: "inherited bone marrow failure syndromes," "hematological neoplasms," "gene expression regulation, leukemic," "RUNX1 protein, human," "RUNX1 protein, mouse," and "Neutropenia, Severe Congenital, Autosomal recessive." Three studies published in 2020 were identified as meeting our inclusion and exclusion criteria. Leukemic progression in severe congenital neutropenia was used as a disease model to evaluate the clinical, molecular, and mechanistic basis of mutations identified in hematological malignancies. Studies in mice and genetically reprogrammed or induced pluripotent stem cells (iPSCs) have shown that isolated mutations are weakly leukemogenic and only initiate hyperproduction of immature hematopoietic cells when in combination with () mutations. Despite this, whole-exome sequencing (WES) performed on leukemogenic transformed cells revealed that all AML cells had an additional mutation in the () gene that caused hyperproduction of the ten-eleven translocation (TET2) protein. This protein causes inflammation in cells with mutations. This process is thought to be critical for clonal myeloid malignant transformation (CMMT) of leukemogenic cells. In conclusion, the combinations of and mutations have a prominent effect on myeloid differentiation resulting in the hyperproduction of myeloblasts. In other studies, it has been noted that the mutations in and genes are not sufficient for the full transformation of leukemogenic cells to AML, and an additional clonal mutation in the gene is essential for full transformation to occur. These data have implicitly demonstrated that mutations are critical in the pathogenesis of various hematological malignancies, and further investigations into the role of are paramount for the development of new cancer treatments.
PubMed: 35765406
DOI: 10.7759/cureus.25372 -
Gels (Basel, Switzerland) Jun 2022Organoids are novel in vitro cell culture models that enable stem cells (including pluripotent stem cells and adult stem cells) to grow and undergo self-organization... (Review)
Review
Organoids are novel in vitro cell culture models that enable stem cells (including pluripotent stem cells and adult stem cells) to grow and undergo self-organization within a three-dimensional microenvironment during the process of differentiation into target tissues. Such miniature structures not only recapitulate the histological and genetic characteristics of organs in vivo, but also form tissues with the capacity for self-renewal and further differentiation. Recent advances in biomaterial technology, particularly hydrogels, have provided opportunities to improve organoid cultures; by closely integrating the mechanical and chemical properties of the extracellular matrix microenvironment, with novel synthetic materials and stem cell biology. This systematic review critically examines recent advances in various strategies and techniques utilized for stem-cell-derived organoid culture, with particular emphasis on the application potential of hydrogel technology in organoid culture. We hope this will give a better understanding of organoid cultures for modelling diseases and tissue engineering applications.
PubMed: 35735722
DOI: 10.3390/gels8060379 -
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 -
Alzheimer's Research & Therapy Feb 2022The NIA-AA research framework proposes a purely biological definition of Alzheimer's disease (AD). This implies that AD can be diagnosed based on biomarker...
BACKGROUND
The NIA-AA research framework proposes a purely biological definition of Alzheimer's disease (AD). This implies that AD can be diagnosed based on biomarker abnormalities, irrespective of clinical manifestation. While this brings opportunities, it also raises challenges. We aimed to provide an overview of considerations regarding the disclosure of AD pathology before the onset of dementia.
METHODS
A systematic literature review was conducted and reported according to PRISMA guidelines. We searched PubMed, Embase, APA PsycINFO, and Web of Science Core Collection (on 10 December 2020) for references on conveying AD biomarker results to individuals without dementia. Our query combined variations on the terms Alzheimer's disease, disclosure, or diagnosis, preclinical or prodromal, and biomarkers. Two reviewers independently screened the resulting 6860 titles and abstracts for eligibility and examined 162 full-text records for relevance. We included theoretical articles in English, on communicating amyloid and/or tau results to individuals with mild cognitive impairment, subjective cognitive decline, or normal cognition. MAXQDA-software was used for inductive data analysis.
RESULTS
We included 27 publications. From these, we extracted 26 unique considerations, which we grouped according to their primary relevance to a clinical, personal, or societal context. Clinical considerations included (lack of) validity, utility, and disclosure protocols. Personal considerations covered psychological and behavioral implications, as well as the right to (not) know. Finally, societal considerations comprised the risk of misconception, stigmatization, and discrimination. Overall, views were heterogeneous and often contradictory, with emphasis on harmful effects.
CONCLUSIONS
We found 26 diverse and opposing considerations, related to a clinical, personal, or societal context, which are relevant to diagnosing AD before dementia. The theoretical literature tended to focus on adverse impact and rely on common morality, while the motivation for and implications of biomarker testing are deeply personal. Our findings provide a starting point for clinicians to discuss biomarker-based diagnosis with their patients, which will become even more relevant in light of the conditional approval of a first disease-modifying drug for AD.
Topics: Alzheimer Disease; Amyloid; Biomarkers; Cognitive Dysfunction; Dementia; Disease Progression; Humans
PubMed: 35144684
DOI: 10.1186/s13195-022-00971-3 -
Frontiers in Cardiovascular Medicine 2021Recent research has suggested that cardiac regeneration may have the widely applicable potential of treating heart failure (HF). A comprehensive understanding of the...
Recent research has suggested that cardiac regeneration may have the widely applicable potential of treating heart failure (HF). A comprehensive understanding of the development status of this field is conducive to its development. However, no bibliometric analysis has summarized this field properly. We aimed to analyze cardiac regeneration-related literature over 20 years and provide valuable insights. Publications were collected from the Web of Science Core Collection (WoSCC). Microsoft Excel, VOSviewer, CiteSpace, and alluvial generator were used to analyze and present the data. The collected 11,700 publications showed an annually increasing trend. The United States and Harvard University were the leading force among all the countries and institutions. The majority of articles were published in Circulation Research, and Circulation was the most co-cited journal. According to co-citation analysis, burst detection and alluvial flow map, cardiomyocyte proliferation, stem cells, such as first-and second-generation, extracellular vesicles especially exosomes, direct cardiac reprogramming, macrophages, microRNAs, and inflammation have become more and more popular recently. Cardiac regeneration remains a research hotspot and develops rapidly. How to modify cardiac regeneration endogenously and exogenously may still be the hotspot in the future and should be discussed more deeply.
PubMed: 34966800
DOI: 10.3389/fcvm.2021.789503 -
Cureus Dec 2021The concept of has been taking a new form where scientists and researchers are in pursuance of regenerative medicine. Until now, doctors have "reacted" to disease by... (Review)
Review
The concept of has been taking a new form where scientists and researchers are in pursuance of regenerative medicine. Until now, doctors have "reacted" to disease by treating the symptoms; however, modern medicine is transforming toward regeneration rather than reactive treatment, which is where stem cell therapy comes into the play-the concept of replacing damaged cells with brand new cells that perform the same function better. Stem cell treatment is currently being used to treat autoimmune, inflammatory, neurological, orthopedic, and traumatic disorders, with various research being undertaken for a wide range of diseases. It could also be the answer to anti-aging and a disease-free state. Despite the benefits, numerous errors could prevail in treating patients with stem cells. With the advancement of technology and research in the modern period, medicine is beginning to turn to artificial intelligence (AI) to address the complicated errors that could occur in regenerative medicine. For successful treatment, one must achieve precision and accuracy when analyzing healthy and productive stem cells that possess all the properties of a native cell. This review intends to discuss and study the application of AI in stem cell therapy and how it influences how medicine is practiced, thus creating a path to a regenerative future with negligible adverse effects. The following databases were used for a literature search: PubMed, Google Scholar, PubMed Central, and Institute of Electrical and Electronics Engineers (IEEE) Xplore. After a thorough analysis, studies were chosen, keeping in mind the inclusion and exclusion criteria set by the authors of this review, which comprised reports published within the last six years in the English language. The authors also made sure to include studies that sufficed the quality of each report assessed using appropriate quality appraisal tools, after which eight reports were found to be eligible and were included in this review. This research mainly revolves around machine learning, deep neural networks (DNN), and other subclasses of AI encompassed in these categories. While there are concerns and limitations in implementing various mediums of AI in stem cell therapy, the analysis of the eligible studies concluded that artificial intelligence provides significant benefits to the global healthcare ecosystem in numerous ways, such as determining the viability, functionality, biosafety, and bioefficacy of stem cells, as well as appropriate patient selection. Applying AI to this novelty brings out the precision, accuracy, and a revolution in regenerative medicine. In addition, stem cell therapy is not currently FDA approved (except for the blood-forming stem cells) and, to date, is considered experimental with no clear outline of risks and benefits. Given this limitation, studies are conducted regularly around the world in hopes for a concrete conclusion where technological advances such as AI could help in shaping the future of regenerative medicine.
PubMed: 34873560
DOI: 10.7759/cureus.20083