Types Of Adult Stem Cells Research Articles

Cellular stress and epigenetic regulation in adult stem cells.

Stem cells are a unique class of cells that possess the ability to differentiate and self-renew, enabling them to repair and replenish tissues. To protect and maintain the potential of stem cells, the cells and the environment surrounding these cells (stem cell niche) are highly responsive and tightly regulated. However, various stresses can affect the stem cells and their niches. These stresses are both systemic and cellular and can arise from intrinsic or extrinsic factors which would have strong implications on overall aging and certain disease states. Therefore, understanding the breadth of drivers, namely epigenetic alterations, involved in cellular stress is important for the development of interventions aimed at maintaining healthy stem cells and tissue homeostasis. In this review, we summarize published findings of epigenetic responses to replicative, oxidative, mechanical, and inflammatory stress on various types of adult stem cells.

Azoxymethane-induced carcinogenesis-like model of mouse intestine and mouse embryonic stem cell-derived intestinal organoids.

Tumor modeling using organoids holds potential in studies of cancer development, enlightening both the intracellular and extracellular molecular mechanisms behind different cancer types, biobanking, and drug screening. Intestinal organoids can be generated in vitro using a unique type of adult stem cells which are found at the base of crypts and are characterized by their high Lgr5 expression levels. In this study, we successfully established intestinal cancer organoid models by using both the BALB/c derived and mouse embryonic stem cells (mESCs)-derived intestinal organoids. In both cases, carcinogenesis-like model was developed by using azoxymethane (AOM) treatment. Carcinogenesis-like model was verified by H&E staining, immunostaining, relative mRNA expression analysis, and LC/MS analysis. The morphologic analysis demonstrated that the number of generated organoids, the number of crypts, and the intensity of the organoids were significantly augmented in AOM-treated intestinal organoids compared to non-AOM-treated ones. Relative mRNA expression data revealed that there was a significant increase in both Wnt signaling pathway-related genes and pluripotency transcription factors in the AOM-induced intestinal organoids. We successfully developed simple carcinogenesis-like models using mESC-based and Lgr5 + stem cell-based intestinal organoids. Intestinal organoid based carcinogenesi models might be used for personalized cancer therapy in the future.

Menstrual blood-derived mesenchymal stem cells combined with collagen I gel as a regenerative therapeutic strategy for degenerated disc after discectomy in rats

BackgroundAnnulus fibrosis (AF) defects have been identified as the primary cause of disc herniation relapse and subsequent disc degeneration following discectomy. Stem cell-based tissue engineering offers a promising approach for structural repair. Menstrual blood-derived mesenchymal stem cells (MenSCs), a type of adult stem cell, have gained attention as an appealing source for clinical applications due to their potential for structure regeneration, with ease of acquisition and regardless of ethical issues.MethodsThe differential potential of MenSCs cocultured with AF cells was examined by the expression of collagen I, SCX, and CD146 using immunofluorescence. Western blot and ELISA were used to examine the expression of TGF-β and IGF-I in coculture system. An AF defect animal model was established in tail disc of Sprague-Dawley rats (males, 8 weeks old). An injectable gel containing MenSCs (about 1*106/ml) was fabricated and transplanted into the AF defects immediately after the animal model establishment, to evaluate its repairment properties. Disc degeneration was assessed via magnetic resonance (MR) imaging and histological staining. Immunohistochemical analysis was performed to assess the expression of aggrecan, MMP13, TGF-β and IGF-I in discs with different treatments. Apoptosis in the discs was evaluated using TUNEL, caspase3, and caspase 8 immunofluorescence staining.ResultsCoculturing MenSCs with AF cells demonstrated ability to express collagen I and biomarkers of AF cells. Moreover, the coculture system presented upregulation of the growth factors TGF-β and IGF-I. After 12 weeks, discs treated with MenSCs gel exhibited significantly lower Pffirrmann scores (2.29 ± 0.18), compared to discs treated with MenSCs (3.43 ± 0.37, p < 0.05) or gel (3.71 ± 0.29, p < 0.01) alone. There is significant higher MR index in disc treated with MenSCs gel than that treated with MenSCs (0.51 ± 0.05 vs. 0.24 ± 0.04, p < 0.01) or gel (0.51 ± 0.05 vs. 0.26 ± 0.06, p < 0.01) alone. Additionally, MenSCs gel demonstrated preservation of the structure of degenerated discs, as indicated by histological scoring (5.43 ± 0.43 vs. 9.71 ± 1.04 in MenSCs group and 10.86 ± 0.63 in gel group, both p < 0.01), increased aggrecan expression, and decreased MMP13 expression in vivo. Furthermore, the percentage of TUNEL and caspase 3-positive cells in the disc treated with MenSCs Gel was significantly lower than those treated with gel alone and MenSCs alone. The expression of TGF-β and IGF-I was higher in discs treated with MenSCs gel or MenSCs alone than in those treated with gel alone.ConclusionMenSCs embedded in collagen I gel has the potential to preserve the disc structure and prevent disc degeneration after discectomy, which was probably attributed to the paracrine of growth factors of MenSCs.

Conditioned Media from Deer Antler Stem Cells Effectively Alleviate Type 1 Diabetes Mellitus Possibly via Inhibiting the NF-κB Signaling Pathway.

Type 1 diabetes mellitus (T1D) represents a severe threat to human health. Persistent hyperglycemia and dyslipidemia can lead to damaged liver function, while effective interventions for these complications are currently lacking. Deer antler stem cells (AnSCs), a novel type of adult stem cells, significantly reduced liver injury, which was speculated to be achieved through the paracrine pathway. In this study, AnSC-conditioned medium (AnSC-CM) was used to treat C57BL/6 mice with T1D symptoms induced by streptozotocin (STZ). The therapeutic effects of AnSC-CM on T1D were evaluated, and the underlying mechanism was investigated. It was shown that AnSC-CM alleviated the T1D symptom: decreased body weight, increased blood glucose levels and islet lesions, and reduced insulin secretion. Moreover, AnSC-CM treatment improved liver function and mitigated liver injury in T1D mice. Impressively, the therapeutic effects of AnSC-CM on T1D were better than those of bone marrow mesenchymal stem cell-CM (BMSC-CM). The mechanistic study revealed that AnSC-CM significantly downregulated the NF-κB signaling pathway in both pancreatic and liver tissues. Therapeutic effects of AnSC-CM on STZ-induced T1D and liver injury may be achieved through targeting the NF-κB signaling pathway.

Stem Cells Reprogramming in Diabetes Mellitus and Diabetic Complications: Recent Advances.

The incidence of diabetes mellitus (DM) is dramatically increasing worldwide, and it is expected to affect 700 million cases by 2045. Diabetes influences health care economics, human quality of life, morbidity, and mortality, which were primarily seen extensively in developing countries. Uncontrolled DM, which results in consistent hyperglycemia, may lead to severe life-threatening complications such as nephropathy, retinopathy, neuropathy, and cardiovascular complications. In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin-producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations. This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

Three-Dimensional Cell Culture of Epididymal Basal Cells and Organoids: A Novel Tool for Toxicology.

Spermatozoa are formed in the testis but must transit through the epididymis to acquire motility and the ability to fertilize. The epididymis is a single convoluted tubule comprising several anatomically and physiologically distinct regions. The pseudostratified epithelium consists of multiple cell types, including principal cells, clear cells, narrow cells, and apical cells, that line the lumen of the epididymis. Basal cells are present at the base of the epithelium, and halo cells, which includes macrophages/monocytes, mononuclear phagocytes, and T lymphocytes, are also present in the epithelium. Several aspects of this complex spermatozoan maturation process are well established, but a great deal remains poorly understood. Given that dysfunction of the epididymis has been associated with male infertility, in vitro tools to study epididymal function and epididymal sperm maturation are required. Our lab and others have previously developed human, rat, and mouse epithelial principal cell lines, which have been used to address certain questions, such as about the regulation of junctional proteins in the epididymis, as well as the toxicity of nonylphenols. Given that the epididymal epithelium comprises multiple cell types, however, a 3D in vitro model provides a more comprehensive and realistic tool that can be used to study and elucidate the multiple aspects of epididymal function. The purpose of this article is to provide detailed information regarding the preparation, maintenance, passaging, and immunofluorescent staining of rat epididymal organoids derived from adult basal cells, which we have demonstrated to be a type of adult stem cell in the rat epididymis. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation of epididymal cells Basic Protocol 2: Magnetic activated cell sorting and isolation of basal cells Basic Protocol 3: Preparation and culture of epididymal basal cell organoids Basic Protocol 4: Passage of epididymal basal cell organoids Basic Protocol 5: Freezing and thawing of epididymal basal cell organoids Basic Protocol 6: Immunofluorescent staining of epididymal basal cell organoids.

Metformin-mediated effects on mesenchymal stem cells and mechanisms: proliferation, differentiation and aging.

Mesenchymal stem cells (MSCs) are a type of pluripotent adult stem cell with strong self-renewal and multi-differentiation abilities. Their excellent biological traits, minimal immunogenicity, and abundant availability have made them the perfect seed cells for treating a wide range of diseases. After more than 60years of clinical practice, metformin is currently one of the most commonly used hypoglycaemic drugs for type 2 diabetes in clinical practice. In addition, metformin has shown great potential in the treatment of various systemic diseases except for type 2 diabetes in recent years, and the mechanisms are involved with antioxidant stress, anti-inflammatory, and induced autophagy, etc. This article reviews the effects and the underlying mechanisms of metformin on the biological properties, including proliferation, multi-differentiation, and aging, of MSCs in vitro and in vivo with the aim of providing theoretical support for in-depth scientific research and clinical applications in MSCs-mediated disease treatment.

Antler stem cell exosomes alleviate pulmonary fibrosis via inhibiting recruitment of monocyte macrophage, rather than polarization of M2 macrophages in mice

Pulmonary fibrosis (PF), a chronic interstitial lung disease, is characterized by over-abundant deposition of extracellular matrix consisting mainly of collagen I. In previous studies, we demonstrated that deer antler stem cells (AnSCs), a novel type of adult stem cell, are capable of significantly down-regulating collagen formation in different organs and tissues and speculated that they could effectively treat PF via reducing collagen deposition in the lung tissue. In the present study, we found that administration of AnSCs improved the survival rate of PF mice and reduced lung fibrosis, collagen deposition and myofibroblast differentiation. The effects of AnSC treatment were significantly better than the positive control (adipose-derived stem cells). Interestingly, AnSC-Exos were almost equally effective as AnSCs in treating PF, suggesting that the effects of AnSCs on reduction of PF may be mainly through a paracrine mechanism. Further, AnSC-Exos reduced the number of M2 macrophages, a type of macrophage that secrets pro-fibrotic factors to accelerate fibrotic progression, in the lung tissues. In vitro experiments showed that the effects of AnSC-Exos on macrophage modulation were likely achieved via inhibition of the recruitment of circulating monocyte-derived macrophages (reducing the number of macrophages), rather than via inhibition of M2 polarization of macrophages. Inhibition of macrophage recruitment by AnSCs may be achieved indirectly via inhibiting CCL7 expression in fibroblasts; both let-7b and let-7a were highly enriched in AnSC-Exos and may play a critical role in the inhibition of CCL7 expression of fibroblasts. Collectively, the use of antler stem cells or their exosomes opens up a novel strategy for PF treatment in the clinical setting.

Use of mesenchymal stem cells to enhance or restore fertility potential: a systematic review of available experimental strategies.

To what extent does regenerative medicine with stem cell therapy help to address infertility issues for future clinical application? Regenerative medicine using different stem cell sources is yielding promising results in terms of protecting the ovarian reserve from damage and senescence, and improving fertility potential in various preclinical settings. Regenerative medicine using stem cell therapy is emerging as a potential strategy to address a number of issues in the field of human reproduction. Indeed, different types of adult and fetal mesenchymal stem cells (MSCs) have been tested with promising results, owing to their ability to differentiate into different tissue lineages, move toward specific injured sites (homing), and generate a secretome with wound-healing, proangiogenic, and antioxidant capacities. Guided by the checklist for preferred reporting items for systematic reviews and meta-analyses, we retrieved relevant studies from PubMed, Medline, and Embase databases until June 2023 using the following keywords: 'mesenchymal stem cells' AND 'ovarian follicles' OR 'ovarian tissue culture' OR 'ovarian follicle culture' OR 'cumulus oocyte complex'. Only peer-reviewed published articles written in English were included. The primary outcome for the experimental strategies was evaluation of the ovarian reserve, with a focus on follicle survival, number, and growth. Secondary outcomes involved analyses of other parameters associated with the follicle pool, such as hormones and growth factors, ovarian tissue viability markers including oxidative stress levels, oocyte growth and maturation rates, and of course pregnancy outcomes. Preclinical studies exploring MSCs from different animal origins and tissue sources in specific conditions were selected (n = 112), including: in vitro culture of granulosa cells, ovarian tissue and isolated ovarian follicles; ovarian tissue transplantation; and systemic or intraovarian injection after gonadotoxic or age-related follicle pool decline. Protecting the ovarian reserve from aging and gonadotoxic damage has been widely tested in vitro and in vivo using murine models and is now yielding initial data in the first ever case series of patients with premature ovarian insufficiency. Use of MSCs as feeder cells in ovarian tissue culture was found to improve follicle outcomes and oocyte competence, bringing us one step closer to future clinical application. MSCs also have proved effective at boosting revascularization in the transplantation site when grafting ovarian tissue in experimental animal models. While preclinical results look promising in terms of protecting the ovarian reserve in different experimental models (especially those in vitro using various mammal experimental models and in vivo using murine models), there is still a lot of work to do before this approach can be considered safe and successfully implemented in a clinical setting. All gathered data on the one hand show that regenerative medicine techniques are quickly gaining ground among innovative techniques being developed for future clinical application in the field of reproductive medicine. After proving MSC effectiveness in preclinical settings, there is still a lot of work to do before MSCs can be safely and effectively used in different clinical applications. This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR T.0077.14, FNRS-CDR J.0063.20, and grant 5/4/150/5 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, and the Fondation St Luc. None of the authors have any competing interest to disclose. N/A.

Harnessing knee joint resident mesenchymal stem cells in cartilage tissue engineering.

Osteoarthritis (OA) is a widespread clinical disease characterized by cartilage degeneration in middle-aged and elderly people. Currently, there is no effective treatment for OA apart from total joint replacement in advanced stages. Mesenchymal stem cells (MSCs) are a type of adult stem cell with diverse differentiation capabilities and immunomodulatory potentials. MSCs are known to effectively regulate the cartilage microenvironment, promote cartilage regeneration, and alleviate OA symptoms. As a result, they are promising sources of cells for OA therapy. Recent studies have revealed the presence of resident MSCs in synovial fluid, synovial membrane, and articular cartilage, which can be collected as knee joint-derived MSCs (KJD-MSC). Several preclinical and clinical studies have demonstrated that KJD-MSCs have great potential for OA treatment, whether applied alone, in combination with biomaterials, or as exocrine MSCs. In this article, we will review the characteristics of MSCs in the joints, including their cytological characteristics, such as proliferation, cartilage differentiation, and immunomodulatory abilities, as well as the biological function of MSC exosomes. We will also discuss the use of tissue engineering in OA treatment and introduce the concept of a new generation of stem cell-based tissue engineering therapy, including the use of engineering, gene therapy, and gene editing techniques to create KJD-MSCs or KJD-MSC derivative exosomes with improved functionality and targeted delivery. These advances aim to maximize the efficiency of cartilage tissue engineering and provide new strategies to overcome the bottleneck of OA therapy. STATEMENT OF SIGNIFICANCE: This research will provide new insights into the medicinal benefit of Joint resident Mesenchymal Stem Cells (MSCs), specifically on its cartilage tissue engineering ability. Through this review, the community will further realize promoting joint resident mesenchymal stem cells, especially cartilage progenitor/MSC-like progenitor cells (CPSC), as a preventive measure against osteoarthritis and cartilage injury. People and medical institutions may also consider cartilage derived MSC as an alternative approach against cartilage degeneration. Moreover, the discussion presented in this study will convey valuable information for future research that will explore the medicinal benefits of cartilage derived MSC.

Characterization of oral-derived neural crest-derived stem cell populations (oNCSCs) in the teeth: Therapeutic potential for bone tissue engineering

Oral Neural Crest-Derived Stem Cells (oNCSCs) are a type of adult stem cell that can be isolated from the oral cavity. These stem cells have the ability to differentiate into various cell types, including neurons, glial cells, and adipocytes. oNCSCs have been shown to play a crucial

Mesenchymal Stem Cells: Generalities and Clinical Significance in Feline and Canine Medicine

Mesenchymal stem cells (MSCs) are multipotent cells: they can proliferate like undifferentiated cells and have the ability to differentiate into different types of cells. A considerable amount of research focuses on the potential therapeutic benefits of MSCs, such as cell therapy or tissue regeneration, and MSCs are considered powerful tools in veterinary regenerative medicine. They are the leading type of adult stem cells in clinical trials owing to their immunosuppressive, immunomodulatory, and anti-inflammatory properties, as well as their low teratogenic risk compared with pluripotent stem cells. The present review details the current understanding of the fundamental biology of MSCs. We focus on MSCs’ properties and their characteristics with the goal of providing an overview of therapeutic innovations based on MSCs in canines and felines.

The Discovery of Menstrual Derived Stem Cells and their Therapeutic Effects

Stem cell therapy is the future of medicine as research is ever-growing for uncurable diseases and injuries. Stem cells are difficult to obtain due to ethical conflicts, retrieval difficulties, or high expenses. However, a stem cell line referred to as menstrual derived stem cells (MenSCs) show great potential in addressing all these issues. MenSCs are a type of adult stem cell that can be found in menstrual blood. These cells are considered a valuable source of stem cells due to their ease of accessibility, abundance, and lack of ethical concerns. MenSCs have been found to possess properties similar to other adult stem cells, such as the ability to differentiate into various cell types, including nerve cells, bone cells, and cartilage cells. Research has shown that MenSCs have the potential to be used in regenerative medicine for various conditions, including cardiovascular disease, nervous system repair, spinal cord injuries, liver and lung health, as well as skin repair. Additionally, MenSCs have been found to possess anti-inflammatory and immunomodulatory properties, making them a potential candidate for the treatment of autoimmune diseases. Despite the potential benefits of MenSCs, further research is needed to fully understand their properties and potential uses. Currently, there are ongoing clinical trials to evaluate the safety and efficacy of MenSCs for various conditions.

Hydrogels from TEMPO-Oxidized Nanofibrillated Cellulose Support In Vitro Cultivation of Encapsulated Human Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) are the most prominent type of adult stem cells for clinical applications. Three-dimensional (3D) cultivation of MSCs in biomimetic hydrogels provides a more physiologically relevant cultivation microenvironment for in vitro testing and modeling, thus overcoming the limitations of traditional planar cultivation methods. Cellulose nanofibers are an excellent candidate biomaterial for synthesis of hydrogels for this application, due to their biocompatibility, tunable properties, availability, and low cost. Herein, we demonstrate the capacity of hydrogels prepared from 2,2,6,6-tetramethylpiperidine-1-oxyl -oxidized and subsequently individualized cellulose-nanofibrils to support physiologically relevant 3D in vitro cultivation of human MSCs at low solid contents (0.2-0.5 wt %). Our results show that MSCs can spread, proliferate, and migrate inside the cellulose hydrogels, while the metabolic activity and proliferative capacity of the cells as well as their morphological characteristics benefit more in the lower bulk cellulose concentration hydrogels.

MiR-221/222 Promote Endothelial Differentiation of Adipose-Derived Stem Cells by Regulation of PTEN/PI3K/AKT/mTOR Pathway.

Adipose-derived stem cells (ADSCs) are a type of adult mesenchymal stem cell that show a repair effect on ischemic tissues owing to their capacity for endothelial differentiation. MicroRNA-221/222 (miR-221/222) has been extensively studied in endothelial cells (ECs). However, the mechanism that regulates ADSCs differentiation into ECs remains unknown. In this study, we investigated the effects of miR-221/222-overexpression/silence in ADSCs on endothelial differentiation by constructing lentiviral vectors. Differentiation capacity was assessed by measuring the expression of endothelial markers (CD31, CD34, and CD144). In addition, low-density lipoprotein (LDL) uptake and tube-like formation were performed for evaluation of functional characterization. The PTEN/PI3K/AKT/mTOR signaling pathway was investigated using western blotting to clarify the action mechanism of this gene. The revascularization of miR-221/222-transfeted ADSCs was further verified in a rat hind limb ischemia model. The results confirmed that transfection with miR-221/222 promoted the expression of endothelial markers, LDL uptake, and tube-like formation. As expected, the PI3K/AKT signaling pathway was effectively activated when ADSCs showed high expression of miR-221/222 during endothelial differentiation. Furthermore, injection of miR-221/222 transfected ADSCs significantly improved rat hindlimb ischemia, as evidenced by increased blood flow and structural integrity and reduce inflammatory infiltration. The results of this study suggest that miR-221/222 is essential for endothelial differentiation of ADSCs and provides a novel strategy for modulating vascular formation and ischemic tissue regeneration.

A UNIQUE ADIPOCYTE PROGENITOR POPULATION PROMOTES AGE-RELATED ADIPOSITY

Abstract The average fat mass in adults increases dramatically with age, and older people often suffer from visceral obesity and related adverse metabolic disorders. Unfortunately, how aging leads to fat accumulation is poorly understood. It is known that fat cell (adipocyte) turnover is very low in young mice, similar to that in young humans. Here, we find that mice mimic age-related fat expansion in humans. In vivo lineage tracing shows that massive adipogenesis (the generation of new adipocytes), especially in the visceral fat, is triggered during aging. Thus, in contrast to most types of adult stem cells that exhibit a reduced ability to proliferate and differentiate, the adipogenic potential of adipocyte progenitor cells (APCs) is unlocked by aging. In vivo transplantation and 3D imaging of transplants show that APCs in aged mice cell-autonomously gain high adipogenic capacity. Single-cell RNA sequencing analyses reveal that aging globally remodels APCs. Herein, we identify a novel committed preadipocyte population that is age-specific (CP-A), existing both in mice and humans, with a global activation of proliferation and adipogenesis pathways. CP-A cells display high proliferation and adipogenesis activity, both in vivo and in vitro. LIFR serves as a functional maker of CP-A, which promotes CP-A proliferation. Together, these findings define a new fundamental mechanism involved in fat tissue aging and offer prospects for preventing and treating age-related metabolic disorders.

Mesenchymal Stem Cells Promote Intestinal Mucosal Repair by Positively Regulating the Nrf2/Keap1/ARE Signaling Pathway in Acute Experimental Colitis.

Mesenchymal stem cells (MSCs) are a type of adult pluripotent stem cell that has anti-inflammatory and immunomodulatory effects, and whose conditioned medium (CM) has also been found to be effective. We used MSC and CM enemas to investigate their ameliorative effects in a mouse model of colitis. We employed MSCs, CM, and MSCs + ML385 (an inhibitor of Nrf2) in dextran sodium sulfate (DSS)-induced colitis. Mice were sacrificed on day 8, and the effects of MSC or CM treatment on the levels of inflammation and oxidative stress in colonic epithelial cells were evaluated by histological analyses. MSCs inhibited inflammatory cell infiltration and proinflammatory cytokine expression in the colon. In addition, MSCs reduced extracellular matrix deposition and maintained the mechanical barrier and permeability of colonic epithelial cells. Mechanistically, MSCs activated Nrf2, which then increased HO-1 and NQO-1 levels and downregulated the expression of Keap1 to suppress reactive oxygen species production and MDA generation, accompanied by increases in components of the enzymatic antioxidant system, including SOD, CAT, GSH-Px, and T-AOC. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/Keap1/ARE pathway, we failed to observe protective effects of MSCs in mice with colitis. CM alone also produced some of the therapeutic benefits of MSCs but was not as effective as MSCs. Our data confirmed that MSCs and CM can effectively improve intestinal mucosal repair in experimental colitis and that MSCs can improve this condition by activating the Nrf2/Keap1/ARE pathway.

Strategies to Convert Cells into Hyaline Cartilage: Magic Spells for Adult Stem Cells.

Damaged hyaline cartilage gradually decreases joint function and growing pain significantly reduces the quality of a patient’s life. The clinically approved procedure of autologous chondrocyte implantation (ACI) for treating knee cartilage lesions has several limits, including the absence of healthy articular cartilage tissues for cell isolation and difficulties related to the chondrocyte expansion in vitro. Today, various ACI modifications are being developed using autologous chondrocytes from alternative sources, such as the auricles, nose and ribs. Adult stem cells from different tissues are also of great interest due to their less traumatic material extraction and their innate abilities of active proliferation and chondrogenic differentiation. According to the different adult stem cell types and their origin, various strategies have been proposed for stem cell expansion and initiation of their chondrogenic differentiation. The current review presents the diversity in developing applied techniques based on autologous adult stem cell differentiation to hyaline cartilage tissue and targeted to articular cartilage damage therapy.

P-296 Relationship between the percentage of stem cells and implantation success in women with in-vitro fertilization

Abstract Study question Is there a relationship between the percentage of stem cells in human endometrial stroma during the mid-luteal phase of the menstrual cycle and implantation success? Summary answer Women with successful implantation have significantly higher percentage of endometrial stromal CD117-positive stem cells during the mid-luteal phase of the menstrual cycle. What is known already Human endometrium as a highly regenerative dynamic tissue has a population of certain types of adult stem cells localized in the stroma and epithelium. These cells, including mesenchymal and hematopoietic stromal stem cells, participate in the immense cellular turnover in the human endometrium before and during the implantation process. General adult stem cell markers such as CD117 and NOTCH1 have been identified in human endometrium. However, there is a scarce data about the quantity of these endometrial stromal stem cells and their influence on the process of implantation. Study design, size, duration This is a cohort study of 109 women who had an endometrial biopsy during the mid-lutheal phase (LH + 7) in a natural cycle and positive or negative hCG test after in-vitro fertilization (IVF) with euploid embryos within 6 months of biopsy. We used immunohistochemical biomarkers NOTCH1 (E-AB-12815, Elabscience), CD117 (CD117/c-Kit/SCF-Receptor) (RB-9038-RQ, Epredia), to identify stem cells in endometrial stroma. The study was conducted between March 2020 and January 2022. Participants/materials, setting, methods The percentages of NOTCH1-positive and CD117-positive stem cells in the stroma were calculated after enumeration by two independent investigators in multiple endometrial sections. After embryo transfer women were divided into the following groups: unsuccessful embryo implantation (negative hCG test) ( n = 45) and successful implantation (positive hCG test) ( n = 64). The percentage of NOTCH1-positive and CD117-positive cells in the endometrial stroma were compared between these groups through Wilcoxon signed-rank test. Main results and the role of chance The percentage of CD117-positive stem cells in the endometrial stroma ranged between 0% and 0.21%, with a median of 0.02%. The percentage of NOTCH1-positive stem cells in the endometrial stroma ranged between 0.003% and 2.11%, with a median of 0.06%. There was no significant difference in female age (years), BMI (kg/m2) and blastocyst quality between the studied patient groups (P &amp;lt; 0.05). The quantity of NOTCH1-positive cells also did not differ significantly between the two groups (P = 0.18). However, the mean percentage of CD117-positive stromal cells was significantly higher in women with successful implantation compared to patients with unsuccessful implantation (0.04% vs. 0.02%, respectively, P = 0.004). The optimal successful implantation cut-off value for the percentage of CD117-positive stromal cells, was 0.018% (AUC 0.67, 95% CI 0.56-0.77). Therefore, a percentage of 0.018% of CD117-positive stem cells in the endometrial stroma was associated with 63.1% sensitivity and 61.4% specificity for predicting successful implantation after IVF. Limitations, reasons for caution The study cohort was limited in sample size. Not all confounding factors such as potential immunological and genetic reasons for unsuccessful implantation have been taken into account. In addition, the endometrial biopsy could also have an effect on endometrial receptivity and pregnancy outcome. Wider implications of the findings The results of this study revealed that the quantity of certain types of stem cells is associated with successful embryo implantation. These findings emphasize the essential impact of stem cells in human endometrium on the process of implantation. Trial registration number not applicable

Cryopreservation of porcine skin-derived stem cells using melatonin or trehalose maintains their ability to self-renew and differentiate

Porcine skin-derived stem cells (pSDSCs) are a type of adult stem cells (ASCs) that retain the ability to self-renew and differentiate. Currently, pSDSCs research has entered an intense period of development; however there has been no research regarding methods of cryopreservation. In this paper, we explored an efficient cryopreservation method for pSDSCs. Our results demonstrated that cryopreserving 50 μm diameter pSDSCs aggregates resulted in a lower apoptosis rate and a greater ability to proliferate to form larger spherical cell aggregates than during single-cell cryopreservation. To further optimize the cryopreservation method, we added different concentrations of melatonin (N-acetyl-5-methoxytryptamine, MLT) and trehalose (d-trehalose anhydrous, TRE) to act as cryoprotectants (CPAs) for the pSDSCs. After comparative experiments, we found that the cryopreservation efficiency of 50 mM TRE was superior. Further experiments demonstrated that the reason why 50 mM TRE improved cryopreservation efficiency was that it reduced the intracellular oxidative stress and mitochondrial damage caused by cryopreservation. Taken together, our results suggest that cryopreserving 50 μm diameter pSDSCs aggregates in F12 medium with 10% dimethyl sulfoxide (DMSO) and 50 mM TRE promotes the long-term storage of pSDSCs.