Application Of Stem Cells Research Articles

AI-organoid integrated systems for biomedical studies and applications.

In this review, we explore the growing role of artificial intelligence (AI) in advancing the biomedical applications of human pluripotent stem cell (hPSC)-derived organoids. Stem cell-derived organoids, these miniature organ replicas, have become essential tools for disease modeling, drug discovery, and regenerative medicine. However, analyzing the vast and intricate datasets generated from these organoids can be inefficient and error-prone. AI techniques offer a promising solution to efficiently extract insights and make predictions from diverse data types generated from microscopy images, transcriptomics, metabolomics, and proteomics. This review offers a brief overview of organoid characterization and fundamental concepts in AI while focusing on a comprehensive exploration of AI applications in organoid-based disease modeling and drug evaluation. It provides insights into the future possibilities of AI in enhancing the quality control of organoid fabrication, label-free organoid recognition, and three-dimensional image reconstruction of complex organoid structures. This review presents the challenges and potential solutions in AI-organoid integration, focusing on the establishment of reliable AI model decision-making processes and the standardization of organoid research.

Application of adipose-derived stem cells in ischemic heart disease: theory, potency, and advantage.

Adipose-derived mesenchymal stem cells (ASCs) represent an innovative candidate to treat ischemic heart disease (IHD) due to their abundance, renewable sources, minor invasiveness to obtain, and no ethical limitations. Compared with other mesenchymal stem cells, ASCs have demonstrated great advantages, especially in the commercialization of stem cell-based therapy. Mechanistically, ASCs exert a cardioprotective effect not only through differentiation into functional cells but also via robust paracrine of various bioactive factors that promote angiogenesis and immunomodulation. Exosomes from ASCs also play an indispensable role in this process. However, due to the distinct biological functions of ASCs from different origins or donors with varing health statuses (such as aging, diabetes, or atherosclerosis), the heterogeneity of ASCs deserves more attention. This prompts scientists to select optimal donors for clinical applications. In addition, to overcome the primary obstacle of poor retention and low survival after transplantation, a variety of studies have been dedicated to the engineering of ASCs with biomaterials. Besides, clinical trials have confirmed the safety and efficacy of ASCs therapy in the context of heart failure or myocardial infarction. This article reviews the theory, efficacy, and advantages of ASCs-based therapy, the factors affecting ASCs function, heterogeneity, engineering strategies and clinical application of ASCs.

Adult stem cells in the eye: Identification, characterisation, and therapeutic application in ocular regeneration - A review.

Adult stem cells, present in various parts of the human body, are undifferentiated cells that can proliferate and differentiate to replace dying cells within tissues. Stem cells have specifically been identified in the cornea, trabecular meshwork, crystalline lens, iris, ciliary body, retina, choroid, sclera, conjunctiva, eyelid, lacrimal gland, and orbital fat. The identification of ocular stem cells broadens the potential therapeutic strategies for untreatable eye diseases. Currently, stem cell transplantation for corneal and conjunctival diseases remains the most common stem cell-based therapy in ocular clinical management. Lens epithelial stem cells have been applied in the treatment of paediatric cataracts. Several early-phase clinical trials for corneal and retinal regeneration using ocular stem cells are also underway. Extensive preclinical studies using ocular stem cells have been conducted, showing encouraging outcomes. Ocular stem cells currently demonstrate great promise in potential treatments of eye diseases. In this review, we focus on the identification, characterisation, and therapeutic application of adult stem cells in the eye.

Perinatal Tissue-Derived Stem Cells: An Emerging Therapeutic Strategy for Challenging Neurodegenerative Diseases.

Over the past 20 years, stem cell therapy has been considered a promising option for treating numerous disorders, in particular, neurodegenerative disorders. Stem cells exert neuroprotective and neurodegenerative benefits through different mechanisms, such as the secretion of neurotrophic factors, cell replacement, the activation of endogenous stem cells, and decreased neuroinflammation. Several sources of stem cells have been proposed for transplantation and the restoration of damaged tissue. Over recent decades, intensive research has focused on gestational stem cells considered a novel resource for cell transplantation therapy. The present review provides an update on the recent preclinical/clinical applications of gestational stem cells for the treatment of protein-misfolding diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). However, further studies should be encouraged to translate this promising therapeutic approach into the clinical setting.

Biocompatibility of hydrogel derived from equine tendon extracellular matrix in horses subcutaneous tissue.

Tendinopathies account for a substantial proportion of musculoskeletal injuries. To improve treatment outcomes for partial and total tendon ruptures, new therapies are under investigation. These include the application of mesenchymal stem cells (MSCs) and biocompatible scaffolds derived from the Extracellular Matrix (ECM). Synthetic polymer hydrogels have not demonstrated results as promising as those achieved with ECM hydrogels sourced from the original tissue. This study aimed to evaluate the biocompatibility of a hydrogel formulated from equine tendon ECM. Six horses were administered three subcutaneous doses of the hydrogel, with a saline solution serving as a control. Biopsies were conducted on days 7, 14, and 56 post-application to gauge the hydrogel's impact. Throughout the experiment, the horse's physical condition remained stable. Thermographic analyses revealed a temperature increase in the treated groups compared to the control group within the initial 12h. The von Frey test, used to measure the mechanical nociceptive threshold, also showed significant differences between the treated group and the control group at 6h, 21 days, and 28 days. Histopathological analyses identified an inflammatory response on day 7, which was absent on days 14 and 56. Transmission electron microscopy indicated a decrease in inflammatory cellularity, while immunohistochemistry staining suggested an increased presence of inflammatory factors on day 14. In summary, the hydrogel is easily injectable, triggers a temporary local inflammatory response, and integrates into the adjacent tissue from day 14 onwards.

Rapid human genomic DNA cloning into mouse artificial chromosome via direct chromosome transfer from human iPSC and CRISPR/Cas9-mediated translocation.

A 'genomically' humanized animal stably maintains and functionally expresses the genes on human chromosome fragment (hCF; <24 Mb) loaded onto mouse artificial chromosome (MAC); however, cloning of hCF onto the MAC (hCF-MAC) requires a complex process that involves multiple steps of chromosome engineering through various cells via chromosome transfer and Cre-loxP chromosome translocation. Here, we aimed to develop a strategy to rapidly construct the hCF-MAC by employing three alternative techniques: (i) application of human induced pluripotent stem cells (hiPSCs) as chromosome donors for microcell-mediated chromosome transfer (MMCT), (ii) combination of paclitaxel (PTX) and reversine (Rev) as micronucleation inducers and (iii) CRISPR/Cas9 genome editing for site-specific translocations. We achieved a direct transfer of human chromosome 6 or 21 as a model from hiPSCs as alternative human chromosome donors into CHO cells containing MAC. MMCT was performed with less toxicity through induction of micronucleation by PTX and Rev. Furthermore, chromosome translocation was induced by simultaneous cleavage between human chromosome and MAC by using CRISPR/Cas9, resulting in the generation of hCF-MAC containing CHO clones without Cre-loxP recombination and drug selection. Our strategy facilitates rapid chromosome cloning and also contributes to the functional genomic analyses of human chromosomes.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

The Novel Application of Stem Cells And Tissue Engineering In Medicine And Dentistry

The Novel Application of Stem Cells And Tissue Engineering In Medicine And Dentistry

The effects of Wharton's jelly MSCs secretomes for restoring busulfan-induced reproductive toxicity in male mice.

Several studies investigated the application of Mesenchymal stem cells (MSCs) for treating spermatogenic disorders. Considering the limitation of MSC application, the present study aimed to compare Wharton's jelly MSCs secretomes, including condition medium (CM) 10-fold concentrated (CM10), 20-fold concentrated CM (CM20), and extracellular vesicles (EVs) to restore busulfan-induced damage on male mice reproduction. So, Wharton's jelly MSCs were cultured, CM was collected, and EVs were isolated. Seventy-two mice were randomly assigned to nine groups, including Control, Busulfan 1 month (1M), Busulfan 2 months (2M), CM10, Busulfan + CM10, CM20, Busulfan + CM20, EVs, and Busulfan + EVs groups. Sperm characteristics, DNA maturity, DNA fragmentation index (DFI), and testicular gene expression were evaluated. Data analysis revealed that CM10 significantly improved sperm plasma membrane integrity, sperm DNA maturity, and DFI in the Busulfan + CM10 group compared to the Busulfan 2M group. Although CM20 and EVs showed a non-significant improvement. Gene expression analysis showed busulfan administration significantly decreased the expression of AR, CREB1, and PLCζ genes, while CM10 significantly restored CREB1 gene expression. The present study demonstrated that CM10 is more effective than CM20 or EVs in reducing busulfan-induced reproductive toxicity.

Mesenchymal stem cells in animal reproduction: sources, uses and scenario.

Studies regarding mesenchymal stem cells turned up in the 1960's and this cell type created a great number of questions about its functions and applicability in science and medicine. When used with therapeutic intent, these cells present an inclination to migrate to sites of injury, inflammation or disease, where they secrete bioactive factors that stimulates the synthesis of new tissue. In this context, studies using rodents reported that MSCs promoted positive effects in the ovarian function in mice with premature aging of follicular reserve. In female bovines, experimental stem cell-based therapies have been used to either generate new oocytes with in vitro quality or stimulate such action in vivo. It is also reported, that the intraovarian application of mesenchymal stem cells generates a greater production of embryos in vitro and the production of early and expanded blastocysts. Additionally, analysis of ovarian tissue in animal subjected to treatment showed an increase in the number of developing follicles. Nevertheless, the treatments involving stem cells with different modes of application, different sources and different species were able to act on the hormonal, tissue, cellular and metabolic levels, generating positive results in the recovery and improvement of ovarian functions.

Adult Mesenchymal Stem Cells in Presence of Glycosaminoglycans.

The application of adult mesenchymal stem cells (MSCs) in the field of tissue regeneration is of increasing interest to the scientific community. In particular, scaffolds and/or hydrogel based on glycosaminoglycans (GAGs) play a pivotal role due to their ability to support the in vitro growth and differentiation of MSCs toward a specific phenotype. Here, we describe different possible approaches to develop GAGs-based biomaterials, hydrogel, and polymeric viscous solutions in order to assess/develop a suitable biomimetic environment. To sustain MSCs viability and promote their differentiation for potential therapeutic applications.

Preventive effect of human umbilical cord mesenchymal stem cells on skin aging in rats

The irreversibility of aging makes anti-aging become an important research direction in the field of medical research. As the most direct manifestation of human aging, skin aging has been paid more and more attention. Stem cells have been used as a basis for anti-aging studies in skin, of which adipose-derived mesenchymal stem cells are more commonly used. In this study, human umbilical cord mesenchymal stem cells were used, and human umbilical cord mesenchymal stem cells were intervened while making a skin aging model, which was planned to reduce the process of preventing skin aging in the study method. At the end of the experiment, rat skin and serum were taken for relevant data detection. The results showed that the contents of EGF and VEGF in serum and skin tissue of rats increased and the content of MDA decreased after the application of human umbilical cord mesenchymal stem cells. At the same time, hUCMSC intervention increased skin thickness, increased dermal vessels, increased type I collagen type III collagen mRNA expression, and decreased MMP-1 content in rats. The results showed that hUCMSC could prevent skin aging in rats.

The Potential Role of Intestinal Stem Cells and Microbiota for the Treatment of Colorectal Cancer.

Colorectal cancer is a global health concern with high incidence and mortality rates. Conventional treatments like surgery, chemotherapy, and radiation therapy have limitations in improving patient survival rates. Recent research highlights the role of gut microbiota and intestinal stem cells in maintaining intestinal health and their potential therapeutic applications in colorectal cancer treatment. The interaction between gut microbiota and stem cells influences epithelial self-renewal and overall intestinal homeostasis. Novel therapeutic approaches, including immunotherapy, targeted therapy, regenerative medicine using stem cells, and modulation of gut microbiota, are being explored to improve treatment outcomes. Accordingly, this chapter provides an overview of the potential therapeutic applications of gut microbiota and intestinal stem cells in treating colorectal cancer.

Application of Bone Marrow Mesenchymal Stem Cells to Osteogenic Differentiation in Stomatology

Application of Bone Marrow Mesenchymal Stem Cells to Osteogenic Differentiation in Stomatology

Autologous fat grafting and adipose-derived stem cells therapy for acute burns and burn-related scar: A systematic review.

The objective of this study was to analyze all available research on the application of autologous fat grafting (AFG) and adipose-derived stem cells (ADSC) to present evidence-based recommendations, particularly in the clinical treatment of acute burns and burn-related scars. We conducted a systematic search of PubMed, COCHRANE, and EMBASE, as well as a manual search of previous reviews' reference lists up. The risk of bias (RoB) was assessed using RoB 2.0 and ROBINS-I, where appropriate. Six eligible studies were selected (2 randomized clinical trials [RCT], 1 retrospective cohort, and 3 experimental studies) with subjects ranging from 3 to 100. Only one study evaluated the use of AFG for acute burns. Improvements in wound healing, vascularization, scar characteristics, and tissue architecture were generally observed in some studies, supported by molecular markers, while one study reported nonsignificant results. Subjective patient satisfaction was reported to have improved. Functional outcomes improvement in the treated regions was minimal. However, study heterogeneity arose mainly from treatment protocols. Cautious results interpretation due to potential bias, especially in selection and confounding domains, and limited clinical trials are important to note. More studies are needed to evaluate. AFG and ADSC hold potential as valuable treatment options for burn-related scars, supported by a body of evidence, but further well-designed RCT are needed. The efficacy of acute burn settings is yet to be further evaluated since evidence is limited.

Intravitreal application of stem cells and their products does not ameliorate experimental autoimmune uveitis

Aims/Purpose: Stem cell therapy has demonstrated potential therapeutic benefits in various medical disciplines. This study evaluated therapeutic effects of mesenchymal stem cells (MSCs) or their by‐products on intraocular inflammation in experimental autoimmune uveitis (EAU) model.Methods: EAU was induced in C57BL/6J mouse strain through administration of IRBP, Freund's adjuvant and pertussis toxin. Conditioned medium was procured through cultivation of MSCs in serum‐free medium, while MSC supernatant was obtained via MSC centrifugation and membrane removal. Either conditioned medium or MSC supernatant was intravitreally administered unilaterally, typically on day 14 post‐EAU induction. Ocular fundus of mice was documented regularly. Experiments were generally concluded on day 28, with eyes processed for FACS and PCR analysis. Infiltration of retina by inflammatory cells (F4/80, CD11c, CD45, CD80, CD86, CD206) and gene expression of pro‐inflammatory factors (Gfap, Iba‐1, IL‐1, iNOS) were quantified.Results: Across all experiments, clinical grading, FACS, and PCR analysis indicated exacerbation of intraocular inflammation. Post‐intravitreal administration of MSC by‐products into eyes with EAU, increased infiltration of retina by inflammatory cells and upregulation in gene expression of pro‐inflammatory factors were observed. These findings were corroborated in vitro, where co‐culturing of retina with EAU in presence of MSCs or their supernatant did not significantly reduce gene expression of pro‐inflammatory factors. Upsurge in pro‐inflammatory factors was also noted in control experiments on healthy eyes post‐intravitreal injection of no substance, serum‐free medium, PBS, or conditioned medium.Conclusions: No improvement in EAU was observed following application of MSC products, both in vivo and in vitro. Instead, inflammation was more severe. Trauma induced by intravitreal application itself significantly influenced outcome.Financial support: GA UK 309621, SVV UK 260631.

Fundamentals and Translational Applications of Stem Cells and Biomaterials in Dental, Oral and Craniofacial Regenerative Medicine.

Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy, and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics, and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Materials that mimic the microenvironment of the stem cell niche are also presented. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.

Positron emission tomography probes for stem cell monitoring: a review.

Stem cells possess unique self-renewal and differentiation capacities, that are central to cell replacement and tissue regeneration. The therapeutic potential of stem cell applications has garnered increasing attention in recent years for a spectrum of human diseases, from ischemic disorders to oncological challenges. Despite their potential, a comprehensive understanding of the biological behavior, efficacy, and safety of these cells remains elusive, hindering their clinical adoption. This review focuses on the use of positron emission tomography (PET) imaging as a cutting-edge tool for bridging this knowledge gap. PET imaging, a noninvasive diagnostic method, has been highlighted for its ability to monitor cellular dynamics after stem cell transplantation. A variety of molecular probes within the PET framework enable the longitudinal and quantitative evaluation of post-transplant cellular behavior. This discourse systematically delineates various PET probes specifically designed for the in vivo tracking of the stem cell life cycle. These probes offer a pathway to a deeper understanding and more precise evaluation of stem cell behavior post-transplantation. Implementing PET imaging probes can revolutionize the clinical understanding of stem cell behavior, advancing and widening clinical therapeutic applications.

Applications of Mesenchymal Stem Cells in Treatments of Domestic Animals

Mesenchymal stem cells: they have received great attention in the field of regenerative medicine due to their ability to differentiate into different cell types and their ability to secrete a wide range of biologically active molecules that repair and regenerate tissues. Stem cells are usually isolated from bone marrow, adipose tissue, or other adult tissues and can be grown in culture media to generate large numbers of cells. Stem cells are widely used in veterinary medicine: for the treatment of bone diseases, diseases of the respiratory and digestive systems, immune diseases. The therapeutic effect of stem cells is due to the anti-inflammatory and immunomodulatory effects of the cells themselves and their excretory products. In general, the continuous investigation and development of Veterinary key therapies is essential to improve animal health and well-being, promote Translational Medicine, and thereby benefit human health. Mesenchymal stem cells have been studied as a potential treatment for various gastrointestinal diseases in cattle, including inflammatory bowel disease and Colitis. Stem cells can be used to replace damaged or diseased tissue by differentiating between specific cell types required for repair and regeneration. Stem cells can also secrete factors that promote tissue regeneration, which can enhance their therapeutic potential. Diverse alternatives provide an attractive option for the possibility of developing clinical applications of stem cells in veterinary medicine.

Effect of umbilical cord mesenchymal stem cells on hypoxia-inducible factor-1 alpha (HIF-1α) production in arteriovenous fistula (AVF) animal model: A preliminary study.

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that plays a crucial role in cellular responses to hypoxia, such as in the development of intimal hyperplasia, a common complication in arteriovenous fistula (AVF) creation. While the application of umbilical cord mesenchymal stem cells (UC-MSCs) has shown promise in various regenerative medicine applications, including tissue repair and angiogenesis, the effect of UC-MSCs on HIF-1α level in the AVF has not been tested. Therefore, the aim of this study was to evaluate the effect of UC-MSCs administration on HIF-1α levels in the AVF animal model. An experimental study was conducted on 28 local male rabbits (Lepus domestica) using a post-test-only design. The rabbits were divided randomly into four groups: normal rabbit group (negative control), placebo-treated AVF rabbit group (positive control), AVF rabbits treated with in-situ UC-MSCs injection (one dose, 106 UC-MSCs/kg body weight), and AVF rabbits treated with intravenous UC-MSCs (one dose, 106 UC-MSCs/kg body weight (BW). HIF-1α level was measured using ELISA method after 28 days post-treatment. All data were analyzed using the one-way analysis of variance (ANOVA) and continued with the Duncan's post-hoc test. The data indicated that the levels of HIF-1α were different among all four groups (p<0.001). The post-hoc analysis revealed that the HIF-1α levels in both UC-MSC treated groups were significantly lower compared to untreated AVF rabbits (p<0.05). This study suggests that UC-MSCs could be a promising therapy to prevent and reduce intimal hyperplasia in AVF.