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International Journal of Molecular... Jun 2024Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context,... (Review)
Review
Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration.
Topics: Exosomes; Nerve Regeneration; Mesenchymal Stem Cells; Humans; Animals; Tissue Scaffolds; Peripheral Nerve Injuries; Mesenchymal Stem Cell Transplantation
PubMed: 38928194
DOI: 10.3390/ijms25126489 -
Cureus May 2024In exploring therapeutic options for ischemic heart disease (IHD) and heart failure, cell-based cardiac repair has gained prominence. This systematic review delves into... (Review)
Review
In exploring therapeutic options for ischemic heart disease (IHD) and heart failure, cell-based cardiac repair has gained prominence. This systematic review delves into the current state of knowledge surrounding cell-based therapies for cardiac repair. Employing a comprehensive search across relevant databases, the study identifies 35 included studies with diverse cell types and methodologies. Encouragingly, these findings reveal the promise of cell-based therapies in cardiac repair, demonstrating significant enhancements in left ventricular ejection fraction (LVEF) across the studies. Mechanisms of action involve growth factors that stimulate angiogenesis, differentiation, and the survival of transplanted cells. Despite these positive outcomes, challenges persist, including low engraftment rates, limitations in cell differentiation, and variations in clinical reproducibility. The optimal dosage and frequency of cell administration remain subjects of debate, with potential benefits from repeated dosing. Additionally, the choice between autologous and allogeneic stem cell transplantation poses a critical decision. This systematic review underscores the potential of cell-based therapies for cardiac repair, bearing implications for innovative treatments in heart diseases. However, further research is imperative to optimize cell type selection, delivery techniques, and long-term efficacy, fostering a more comprehensive understanding of cell-based cardiac repair.
PubMed: 38832190
DOI: 10.7759/cureus.59474 -
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 -
International Journal of Molecular... Mar 2024Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful... (Review)
Review
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.
Topics: Humans; Endothelial Cells; Quality of Life; Wound Healing; Pluripotent Stem Cells; Intercellular Signaling Peptides and Proteins; Cytokines; Mesenchymal Stem Cell Transplantation
PubMed: 38474251
DOI: 10.3390/ijms25053006 -
Pain Feb 2024Developments in human cellular reprogramming now allow for the generation of human neurons for in vitro disease modelling. This technique has since been used for...
Developments in human cellular reprogramming now allow for the generation of human neurons for in vitro disease modelling. This technique has since been used for chemotherapy-induced peripheral neuropathy (CIPN) research, resulting in the description of numerous CIPN models constructed from human neurons. This systematic review provides a critical analysis of available models and their methodological considerations (ie, used cell type and source, CIPN induction strategy, and validation method) for prospective researchers aiming to incorporate human in vitro models of CIPN in their research. The search strategy was developed with assistance from a clinical librarian and conducted in MEDLINE (PubMed) and Embase (Ovid) on September 26, 2023. Twenty-six peer-reviewed experimental studies presenting original data about human reprogrammed nonmotor neuron cell culture systems and relevant market available chemotherapeutics drugs were included. Virtually, all recent reports modeled CIPN using nociceptive dorsal root ganglion neurons. Drugs known to cause the highest incidence of CIPN were most used. Furthermore, treatment effects were almost exclusively validated by the acute effects of chemotherapeutics on neurite dynamics and cytotoxicity parameters, enabling the extrapolation of the half-maximal inhibitory concentration for the 4 most used chemotherapeutics. Overall, substantial heterogeneity was observed in the way studies applied chemotherapy and reported their findings. We therefore propose 6 suggestions to improve the clinical relevance and appropriateness of human cellular reprogramming-derived CIPN models.
PubMed: 38381959
DOI: 10.1097/j.pain.0000000000003193 -
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 -
Bioengineering (Basel, Switzerland) Jan 2024Hereditary optic neuropathies (HONs) such as dominant optic atrophy (DOA) and Leber Hereditary Optic Neuropathy (LHON) are mitochondrial diseases characterized by a... (Review)
Review
Hereditary optic neuropathies (HONs) such as dominant optic atrophy (DOA) and Leber Hereditary Optic Neuropathy (LHON) are mitochondrial diseases characterized by a degenerative loss of retinal ganglion cells (RGCs) and are a cause of blindness worldwide. To date, there are only limited disease-modifying treatments for these disorders. The discovery of induced pluripotent stem cell (iPSC) technology has opened several promising opportunities in the field of HON research and the search for therapeutic approaches. This systematic review is focused on the two most frequent HONs (LHON and DOA) and on the recent studies related to the application of human iPSC technology in combination with biomaterials technology for their potential use in the development of RGC replacement therapies with the final aim of the improvement or even the restoration of the vision of HON patients. To this purpose, the combination of natural and synthetic biomaterials modified with peptides, neurotrophic factors, and other low- to medium-molecular weight compounds, mimicking the ocular extracellular matrices, with human iPSC or iPSC-derived cell retinal progenitors holds enormous potential to be exploited in the near future for the generation of transplantable RGC populations.
PubMed: 38247929
DOI: 10.3390/bioengineering11010052 -
European Journal of Medical Research Dec 2023Humans' nervous system has a limited ability to repair nerve cells, which poses substantial challenges in treating injuries and diseases. Stem cells are identified by... (Review)
Review
BACKGROUND
Humans' nervous system has a limited ability to repair nerve cells, which poses substantial challenges in treating injuries and diseases. Stem cells are identified by the potential to renew their selves and develop into several cell types, making them ideal candidates for cell replacement in injured neurons. Neuronal differentiation of embryonic stem cells in modern medicine is significant. Nanomaterials have distinct advantages in directing stem cell function and tissue regeneration in this field. We attempted in this systematic review to collect data, analyze them, and report results on the effect of nanomaterials on neuronal differentiation of embryonic stem cells.
METHODS
International databases such as PubMed, Scopus, ISI Web of Science, and EMBASE were searched for available articles on the effect of nanomaterials on neuronal differentiation of embryonic stem cells (up to OCTOBER 2023). After that, screening (by title, abstract, and full text), selection, and data extraction were performed. Also, quality assessment was conducted based on the STROBE checklist.
RESULTS
In total, 1507 articles were identified and assessed, and then only 29 articles were found eligible to be included. Nine studies used 0D nanomaterials, ten used 1D nanomaterials, two reported 2D nanomaterials, and eight demonstrated the application of 3D nanomaterials. The main biomaterial in studies was polymer-based composites. Three studies reported the negative effect of nanomaterials on neural differentiation.
CONCLUSION
Neural differentiation is crucial in neurological regenerative medicine. Nanomaterials with different characteristics, particularly those cellular regulating activities and stem cell fate, have much potential in neural tissue engineering. These findings indicate a new understanding of potential applications of physicochemical cues in nerve tissue engineering.
Topics: Humans; Embryonic Stem Cells; Neurons; Nanostructures; Tissue Engineering; Cell Differentiation
PubMed: 38071365
DOI: 10.1186/s40001-023-01546-0 -
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 -
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