-
Frontiers in Endocrinology 2022Hypothyroidism is a common hormone deficiency disorder. Although hormone supplemental therapy can be easily performed by daily levothyroxine administration, a proportion...
BACKGROUND
Hypothyroidism is a common hormone deficiency disorder. Although hormone supplemental therapy can be easily performed by daily levothyroxine administration, a proportion of patients suffer from persisting complaints due to unbalanced hormone levels, leaving room for new therapeutic strategies, such as tissue engineering and regenerative medicine.
METHODS
Electronic searches of databases for studies of thyroid regeneration or thyroid organoids were performed. A systematic review including both and models of thyroid regenerative medicine was conducted.
RESULTS
Sixty-six independent studies published between 1959 and May 1st, 2022 were included in the current systematic review. Among these 66 studies, the most commonly involved species was human (19 studies), followed by mouse (18 studies), swine (14 studies), rat (13 studies), calf/bovine (4 studies), sheep/lamb (4 studies) and chick (1 study). In addition, in these experiments, the most frequently utilized tissue source was adult thyroid tissue (46 studies), followed by embryonic stem cells (ESCs)/pluripotent stem cells (iPSCs) (10 studies), rat thyroid cell lines (7 studies), embryonic thyroid tissue (2 studies) and newborn or fetal thyroid tissue (2 studies). Sixty-three studies reported relevant thyroid follicular regeneration experiments , while 21 studies showed an experiment section that included transplanting engineered thyroid tissue into recipients. Together, 12 studies were carried out using 2D structures, while 50 studies constructed 3D structures.
CONCLUSIONS
Each aspect of thyroid regenerative medicine was comprehensively described in this review. The recovery of optimal hormonal equilibrium by the transplantation of an engineered functional thyroid holds great therapeutic promise.
Topics: Animals; Humans; Sheep; Cattle; Mice; Rats; Swine; Hypothyroidism; Pluripotent Stem Cells; Induced Pluripotent Stem Cells; Hormones
PubMed: 36531472
DOI: 10.3389/fendo.2022.1065410 -
Biology Sep 2022This systematic scoping review aims to map and identify the available artificial-intelligence-based techniques for imaging analysis, the characterization of stem cell... (Review)
Review
This systematic scoping review aims to map and identify the available artificial-intelligence-based techniques for imaging analysis, the characterization of stem cell differentiation, and trans-differentiation pathways. On the ninth of March 2022, data were collected from five electronic databases (PubMed, Medline, Web of Science, Cochrane, and Scopus) and manual citation searching; all data were gathered in Zotero 5.0. A total of 4422 articles were collected after deduplication; only twenty-seven studies were included in this systematic scoping review after a two-phase screening against inclusion criteria by two independent reviewers. The amount of research in this field is significantly increasing over the years. While the current state of artificial intelligence (AI) can tackle a multitude of medical problems, the consensus amongst researchers remains that AI still falls short in multiple ways that investigators should examine, ranging from the quality of images used in training sets and appropriate sample size, as well as the unexpected events that may occur which the algorithm cannot predict.
PubMed: 36290317
DOI: 10.3390/biology11101412 -
Communications Biology Oct 2022The myriad of available hepatocyte in vitro models provides researchers the possibility to select hepatocyte-like cells (HLCs) for specific research goals. However,...
The myriad of available hepatocyte in vitro models provides researchers the possibility to select hepatocyte-like cells (HLCs) for specific research goals. However, direct comparison of hepatocyte models is currently challenging. We systematically searched the literature and compared different HLCs, but reported functions were limited to a small subset of hepatic functions. To enable a more comprehensive comparison, we developed an algorithm to compare transcriptomic data across studies that tested HLCs derived from hepatocytes, biliary cells, fibroblasts, and pluripotent stem cells, alongside primary human hepatocytes (PHHs). This revealed that no HLC covered the complete hepatic transcriptome, highlighting the importance of HLC selection. HLCs derived from hepatocytes had the highest transcriptional resemblance to PHHs regardless of the protocol, whereas the quality of fibroblasts and PSC derived HLCs varied depending on the protocol used. Finally, we developed and validated a web application (HLCompR) enabling comparison for specific pathways and addition of new HLCs. In conclusion, our comprehensive transcriptomic comparison of HLCs allows selection of HLCs for specific research questions and can guide improvements in culturing conditions.
Topics: Cell Differentiation; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Pluripotent Stem Cells; Transcriptome
PubMed: 36241695
DOI: 10.1038/s42003-022-04046-9 -
Birth Defects Research Oct 2022The dynamics and complexities of in utero fetal development create significant challenges in transitioning from lab animal-centric developmental toxicity testing methods...
BACKGROUND
The dynamics and complexities of in utero fetal development create significant challenges in transitioning from lab animal-centric developmental toxicity testing methods to assessment strategies based on new approach methodologies (NAMs). Nevertheless, considerable progress is being made, stimulated by increased research investments and scientific advances, such as induced pluripotent stem cell-derived models. To help identify developmental toxicity NAMs for toxicity screening and potential funding through the American Chemistry Council's Long-Range Research Initiative, a systematic literature review was conducted to better understand the current landscape of developmental toxicity NAMs.
METHODS
Scoping review tools were used to systematically survey the literature (2010-2021; ~18,000 references identified), results and metadata were then extracted, and a user-friendly interactive dashboard was created.
RESULTS
The data visualization dashboard, developed using Tableau® software, is provided as a free, open-access web tool. This dashboard enables straightforward interactive queries and visualizations to identify trends and to distinguish and understand areas or NAMs where research has been most, or least focused.
CONCLUSIONS
Herein, we describe the approach and methods used, summarize the benefits and challenges of applying the systematic-review techniques, and highlight the types of questions and answers for which the dashboard can be used to explore the many different facets of developmental toxicity NAMs.
Topics: Animals; Software; Toxicity Tests; United States
PubMed: 36205106
DOI: 10.1002/bdr2.2075 -
Tissue Engineering. Part B, Reviews Apr 2023Tissue Engineering (TE) is a branch of Regenerative Medicine (RM) that combines stem cells and biomaterial scaffolds to create living tissue constructs to restore... (Review)
Review
Tissue Engineering (TE) is a branch of Regenerative Medicine (RM) that combines stem cells and biomaterial scaffolds to create living tissue constructs to restore patients' organs after injury or disease. Over the last decade, emerging technologies such as 3D bioprinting, biofabrication, supramolecular materials, induced pluripotent stem cells, and organoids have entered the field. While this rapidly evolving field is expected to have great therapeutic potential, its development from bench to bedside presents several ethical and societal challenges. To make sure TE will reach its ultimate goal of improving patient welfare, these challenges should be mapped out and evaluated. Therefore, we performed a systematic review of the ethical implications of the development and application of TE for regenerative purposes, as mentioned in the academic literature. A search query in PubMed, Embase, Scopus, and PhilPapers yielded 2451 unique articles. After systematic screening, 237 relevant ethical and biomedical articles published between 2008 and 2021 were included in our review. We identified a broad range of ethical implications that could be categorized under 10 themes. Seven themes trace the development from bench to bedside: (1) animal experimentation, (2) handling human tissue, (3) informed consent, (4) therapeutic potential, (5) risk and safety, (6) clinical translation, and (7) societal impact. Three themes represent ethical safeguards relevant to all developmental phases: (8) scientific integrity, (9) regulation, and (10) patient and public involvement. This review reveals that since 2008 a significant body of literature has emerged on how to design clinical trials for TE in a responsible manner. However, several topics remain in need of more attention. These include the acceptability of alternative translational pathways outside clinical trials, soft impacts on society and questions of ownership over engineered tissues. Overall, this overview of the ethical and societal implications of the field will help promote responsible development of new interventions in TE and RM. It can also serve as a valuable resource and educational tool for scientists, engineers, and clinicians in the field by providing an overview of the ethical considerations relevant to their work. Impact statement To our knowledge, this is the first time that the ethical implications of Tissue Engineering (TE) have been reviewed systematically. By gathering existing scholarly work and identifying knowledge gaps, this review facilitates further research into the ethical and societal implications of TE and Regenerative Medicine (RM) and other emerging biomedical technologies. Moreover, it will serve as a valuable resource and educational tool for scientists, engineers, and clinicians in the field by providing an overview of the ethical considerations relevant to their work. As such, our review may promote successful and responsible development of new strategies in TE and RM.
Topics: Animals; Humans; Tissue Engineering; Regenerative Medicine; Biocompatible Materials; Induced Pluripotent Stem Cells; Bioprinting
PubMed: 36112697
DOI: 10.1089/ten.TEB.2022.0033 -
Clinical Ophthalmology (Auckland, N.Z.) 2022Glaucoma is an optic neuropathy disease that causes cupping of the optic disc and decreased visual field. Glaucoma is still the second leading cause of blindness... (Review)
Review
Glaucoma is an optic neuropathy disease that causes cupping of the optic disc and decreased visual field. Glaucoma is still the second leading cause of blindness globally, with a worldwide prevalence of more than 76 million people in 2020. However, no therapy can cure glaucoma completely, especially when optic nerve damage has occurred. Available treatments only play a role in keeping the intraocular pressure stable This research aims to determine the potential use of modified stem cell therapy to treat intraocular damage in glaucoma cases. Literature research was conducted by involving seven online databases, namely Pubmed, ScienceDirect, Proquest, EBSCOhost, SAGE, Clinicalkey, and Scopus, published between 2010-2020 with the keywords stem cells; therapy; glaucoma; optic nerve. Six articles were selected, and out of the six articles, all writings were experimental research. The entire literature states that modified stem cell therapy has the potential as a therapeutic option in treating intraocular damage in patients with glaucoma. Based on the systematic literature review that has been carried out, it is known that stem cell therapy has the potential to be a therapeutic option in treating glaucoma cases. Much more research is needed to assess the effectiveness of modified stem cell therapy in managing intraocular damage due to glaucoma.
PubMed: 36061629
DOI: 10.2147/OPTH.S372114 -
Frontiers in Cardiovascular Medicine 2022Cardiovascular diseases are the leading cause of mortality and reduced quality of life globally. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)...
Cardiovascular diseases are the leading cause of mortality and reduced quality of life globally. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a personalized platform to study inherited heart diseases, drug-induced cardiac toxicity, and cardiac regenerative therapy. However, the immaturity of CMs obtained by current strategies is a major hurdle in utilizing hiPSC-CMs at their fullest potential. Here, the major findings and limitations of current maturation methodologies to enhance the utility of hiPSC-CMs in the battle against a major source of morbidity and mortality are reviewed. The most recent knowledge of the potential signaling pathways involved in the transition of fetal to adult CMs are assimilated. In particular, we take a deeper look on role of nutrient sensing signaling pathways and the potential role of cap-independent translation mediated by the modulation of mTOR pathway in the regulation of cardiac gap junctions and other yet to be identified aspects of CM maturation. Moreover, a relatively unexplored perspective on how our knowledge on the effects of preterm birth on cardiovascular development can be actually utilized to enhance the current understanding of CM maturation is examined. Furthermore, the interaction between the evolving neonatal human heart and brown adipose tissue as the major source of neonatal thermogenesis and its endocrine function on CM development is another discussed topic which is worthy of future investigation. Finally, the current knowledge regarding transcriptional mediators of CM maturation is still limited. The recent studies have produced the groundwork to better understand CM maturation in terms of providing some of the key factors involved in maturation and development of metrics for assessment of maturation which proves essential for future studies on PSC-CMs maturation.
PubMed: 36061558
DOI: 10.3389/fcvm.2022.967659 -
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