In recent years, various clinical trials have been designed and implemented using mesenchymal stem cells (MSCs) for the treatment of heart diseases. Clinical trials exploring MSC-based treatments have proliferated, yet the lack of standardized protocols for MSC administration remains a significant challenge. Despite the growing popularity of MSC trials, questions persist regarding optimal dosing, administration routes, and frequency to achieve safety and efficacy, particularly in the context of cardiac regeneration. The current study has reviewed the clinical trials that have used MSCs for the treatment of heart diseases since 2009. The findings reveal diverse transplantation methods and varying MSCs quantities, highlighting the absence of a universal guideline for MSCs utilization in heart disease clinical trials.

Recently, cell therapies, including chimeric antigen receptor (CAR) modified T cell therapy and mesenchymal stem cell (MSC) therapy, have demonstrated considerable potential for systemic lupus erythematosus (SLE). In this study, a CAR-MSC model was constructed, combining two cell therapies. The structural domains of the CAR were designed by using the anti-CD19 scFv, targeting the CD19 antigen on the surface of B cells and the intracellular region of the interferon-gamma receptor, activating the JAK-STAT1 signaling pathway. Then we screened and identified the most effective structural domain of CAR as CAR1, as it facilitates MSCs to maintain significantly higher levels of JAK2 phosphorylation and IDO expression, as shown by western blot analysis. We also demonstrated CAR1 could be consistently and stably expressed at high levels in MSCs, and CAR1 transduction did not significantly affect the surface antigenic phenotypic criteria of MSCs via flow analysis. Furthermore, immunofluorescence results showed CAR1-MSCs could stably bind CD19 antigen, and they were activated by human CD19 antigen resulting in significantly high JAK2 phosphorylation and IDO expression via western blot analysis following co-culture. Besides, when activated peripheral blood mononuclear cells (PBMCs) were co-cultured with untransduced MSCs (UTD-MSCs) and CAR1-MSCs in vitro, respectively, the results showed that the percentage of activated CD3+ T cells and CD19+ B cells was both significantly lower after co-culturing. The percentage of activated CD19+ B cells was lower in the CAR1-MSCs co-culture group than in the UTD-MSCs co-culture group, whereas the percentage of activated CD3+ T cells was similar in the two co-culture groups. This suggests that CAR1 increased the inhibitory ability of MSCs on activated CD19+ B cells and had no significant effect on the ability of MSCs to inhibit activated CD3+ T cells. In conclusion, CAR1-MSCs were successfully constructed and demonstrated the ability to enhance the inhibitory effect of MSCs on activated human CD19+ B cells, facilitating SLE therapy.

Mesenchymal stem cells (MSCs) have demonstrated significant potential in heart failure (HF) treatment, but the exact mechanisms are still not fully understood. This research utilized single-cell RNA sequencing to examine alterations in peripheral blood mononuclear cells from heart failure patients pre- and post-MSC therapy. Moreover, we utilized Mendelian randomization (MR) analysis to identify causal genes linked to HF. Specifically, through scRNA-seq, we observed a progressive increase in Natural Killer (NK) cells within peripheral blood mononuclear cells (PBMCs) following MSC treatment. Furthermore, MR analysis identified the differentially expressed gene (DEG) BAX as a potential target gene for HF. Notably, the expression of BAX was significantly downregulated after MSC treatment, suggesting its potential as a therapeutic response biomarker. Cell-cell communication analysis revealed that BAXhigh NK cells displayed reduced cell-cell communication and increased apoptotic activity. Enrichment analysis indicated an association between BAXhigh NK cells and the "coagulant" pathway. Taken together, our findings suggest that BAX may contribute to the pathogenesis of HF by promoting coagulation and apoptotic pathways. In contrast, MSCs appear to suppress BAX expression, thereby inhibiting these pathways. MSC treatment increases the proportion of NK cells and reduces BAXhigh NK cells, ultimately improving NK cell function, and ameliorating HF.

Heart failure (HF) remains a leading cause of mortality, responsible for 13% of all deaths worldwide. The prognosis for patients with HF is poor, with only a 50% survival rate within 5 years. A major challenge of ischaemia-driven HF is the loss of cardiomyocytes, compounded by the minimal regenerative capacity of the adult heart. To date, replacement of irreversibly damaged heart muscle can only be achieved by complete heart transplantation. In the past 20 years, cell therapy has emerged and evolved as a promising avenue for cardiac repair and regeneration. During this time, cell therapy for HF has encountered substantial barriers in both preclinical studies and clinical trials but the field continues to progress and evolve from lessons learned from such research. In this Review, we provide an overview of ongoing trials of cell-based and cell product-based therapies for the treatment of HF. Findings from these trials will facilitate the clinical translation of cardiac regenerative and reparative therapies not only by evaluating the safety and efficacy of specific cell-based therapeutics but also by establishing the feasibility of novel or underexplored treatment protocols such as repeated intravenous dosing, personalized patient selection based on pharmacogenomics, systemic versus intramural cell delivery, and epicardial engraftment of engineered tissue products.

Mesenchymal stem cell (MSC) therapy for cardiovascular diseases has shown promise; however, sex-specific differences remain understudied. This scientometric analysis provides the first comprehensive overview of sex-specific differences in mesenchymal stem cell (MSC) therapy for cardiovascular diseases, spanning from 1947 to 2024.

We analyzed 61,029 publications using advanced bibliometric tools to identify research hotspots, publication trends, and collaborative networks.

A significant shift in research focus has been observed in the field of mesenchymal stem cell (MSC) therapy for cardiovascular diseases, transitioning from broad cardiovascular concepts in the 20th century to specialized sex-specific considerations in the 21st century. Furthermore, in the 21st-century research landscape, the formation of two distinct clusters for "male" and "female" in VOSviewer-generated network visualizations is highly important, emphasizing the growing recognition of sex-specific differences in MSC therapy responses and outcomes. This shift was accompanied by a marked increase in terminology related to sex-specific differences, with keywords like "genetic association" and "body mass index" forming distinct clusters in recent years.

This analysis underscores the critical need for sex-specific considerations in MSC therapy for cardiovascular disease. The emergence of distinct male and female clusters in research networks emphasizes the importance of tailoring approaches based on sex differences. Key areas identified for future investigation include the role of epigenetics in mediating sex-specific effects and the potential of sex-matched MSC-derived exosomes. These findings pave the way for more effective and personalized approaches in cardiovascular regenerative medicine, potentially leading to improved outcomes through sex-specific therapeutic strategies.

Heart failure (HF) represents the terminal stage of cardiovascular disease and remains a leading cause of mortality. Epidemiological studies indicate a high prevalence and mortality rate of HF globally. Current treatment options primarily include pharmacological and non-pharmacological approaches. With the development of mesenchymal stem cell (MSC) transplantation technology, increasing research has shown that stem cell therapy and exosomes derived from these cells hold promise for repairing damaged myocardium and improving cardiac function, becoming a hot topic in clinical treatment for HF. However, this approach also presents certain limitations. This review summarizes the mechanisms of HF, current treatment strategies, and the latest progress in the application of MSCs and their exosomes in HF therapy.

Recent randomized controlled trials have consistently demonstrated the safety and potential efficacy of MSC therapy for heart failure patients. This study delves into mesenchymal stem cells' promising potential, offering a beacon of hope for the future of heart failure treatment with reduced ejection fraction (HFrEF).

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for this systematic review and meta-analysis. We searched four databases and registers for RCTs, including PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other relevant websites. We then selected thirteen RCTs with 1184 participants based on our pre-defined inclusion/exclusion criteria. Two independent assessors extracted the data and performed a quality assessment. The data were then plotted for various outcomes, including death, hospitalization, major adverse cardiac events, pump function parameters, and 6-min walk distance.

The safety of MSC-based treatment has been consistently demonstrated with MSCs from autologous (AutoMSCs) and allogeneic (AlloMSCs) sources. This reassuring finding underscores the reliability of MSC-based therapy irrespective of their source. However, AutoMSCs showed a trend toward greater protective benefits. Subgroup analysis revealed no significant differences between AutoMSCs and AlloMSCs in improving LVEF; 0.86% (95% CI - 1.21-2.94%) for AlloMSCs versus 2.17% (- 0.48%; 95% CI - 1.33-5.67%) for AutoMSCs. AlloMSCs significantly reduced end-diastolic volume (LVEDV) by - 2.08 mL (95% CI - 3.52-0.64 mL). Only AlloMSCs significantly improved 6-min walking distance (6-MWD); 31.88 m (95% CI 5.03-58.74 m) for AlloMSCs versus 31.71 m (95% CI - 8.91-71.25 m) for AutoMSCs. The exclusion of studies using adipose-derived cells resulted in even better safety and a significant improvement in LVEF for AlloMSCs treatment.

Our findings suggest that AlloMSCs are at par with AutoMSCs in improving functional outcomes in heart failure patients. This underscores the need for future investigations in a larger patient cohort, emphasizing the urgency and importance of further research to fully understand the potential of MSCs in treating heart failure.

The current medical need to respond to different diseases has sparked great interest in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) due to their great regenerative potential and as drug carriers by playing a critical role in cell-cell communication. However, due to their heterogeneity, there is no standardized universal method for their identification and characterization, which limits their clinical application. This study, following the recommendations and methodologies proposed by MISEV2023 for the characterization of EVs, shows for the first time a detailed morphological, protein, and biochemical comparison between EVs derived from three different MSCs sources (placenta, endometrium, and dental pulp). The information obtained from the different applied assays suggests that there are substantial differences between one EVs source and another. It also offers valuable insights that provide the guidelines to ease their profiling and therefore improve their selection, in order to speed up their use and clinical application; additionally, the knowledge obtained from each characterization test could facilitate new researchers in the field to choose a specific cell source to obtain EVs and select the appropriate methods that provide the necessary information according to their requirements.

Stem cell-based therapy has emerged as a promising approach for heart repair, potentially regenerating damaged heart tissue and improving outcomes for patients with heart disease. However, the efficacy of stem cell-based therapies remains limited by several challenges, including poor cell survival, low retention rates, poor integration, and limited functional outcomes. This article reviews current enhancement strategies to optimize mesenchymal stem cell therapy for cardiac repair. Key approaches include optimizing cell delivery methods, enhancing cell engraftment, promoting cell functions through genetic and molecular modifications, enhancing the paracrine effects of stem cells, and leveraging biomaterials and tissue engineering techniques. By focusing on these enhancement techniques, the paper highlights innovative approaches that can potentially transform stem cell therapy into a more viable and effective treatment option for cardiac repair. The ongoing research and technological advancements continue to push the boundaries, hoping to make stem cell therapy a mainstream treatment for heart disease.

As living biodrugs, mesenchymal stem cells (MSCs) have progressed to phase 3 clinical trials for cardiovascular applications. However, their limited immediate availability hampers their routine clinical use.

To validate our hypothesis that cryopreserved MSCs (CryoMSCs) are as safe and effective as freshly cultured MSC counterparts but carry logistical advantages.

Four databases were systematically reviewed for relevant randomized controlled trials (RCTs) evaluating the safety and efficacy of CryoMSCs from various tissue sources in treating patients with heart disease. A subgroup analysis was performed based on MSC source and post-thaw cell viability to determine treatment effects across different CryoMSCs sources and viability status. Weighted mean differences (WMDs) and odds ratios were calculated to measure changes in the estimated treatment effects. All statistical analyses were performed using RevMan version 5.4.1 software.

Seven RCTs (285 patients) met the eligibility criteria for inclusion in the meta-analysis. During short-term follow-up, CryoMSCs demonstrated a significant 2.11% improvement in left ventricular ejection fraction (LVEF) [WMD (95%CI) = 2.11 (0.66-3.56), P = 0.004, I 2 = 1%], with umbilical cord-derived MSCs being the most effective cell type. However, the significant effect on LVEF was not sustained over the 12 months of follow-up. Subgroup analysis demonstrated a substantial 3.44% improvement in LVEF [WMD (95%CI) = 3.44 (1.46-5.43), P = 0.0007, I 2 = 0%] when using MSCs with post-thaw viability exceeding 80%. There was no statistically significant difference in the frequency of major cardiac adverse events observed in rehospitalization or mortality in patients treated with CryoMSCs vs the control group.

CryoMSCs are a promising option for heart failure patients, particularly considering the current treatment options for cardiovascular diseases. Our data suggest that CryoMSCs could be a viable alternative or complementary treatment to the current options, potentially improving patient outcomes.

The human eye, a photo-sensory organ with an array of neuronal and tissue networks, remains susceptible to damage from various diseases and disorders despite its being a flawless masterpiece. It is estimated that over 2 billion people suffer from vision loss with common causative factors such as; age-related macular degeneration (AMD), glaucoma, cataracts, diabetic retinopathy, and infections amongst others. The use of Orthodox procedures has only helped mitigate the pathology; however, it doesn't serve any substantial curative purpose. More recently, the incorporation of new therapies via ocular delivery of nanomaterials and stem cell intervention has helped to change tides in the treatment of various ophthalmic pathologies.

This review provides an overview of the current trends and breakthroughs in ophthalmology via stem cell therapy, with emphasis on its types, mechanisms, applications, and benefits. Mesenchymal stem cells which can arise from embryonic or adult origin possess some immunomodulatory effects that contribute to the therapeutic relevance of the MSCs and the ability to evade rejection from the host. However, the major drawback has been uncontrolled growth which can result in unintended side effects. Moreso, religious and ethical issues concerning the employment of MSCs from embryonic origin have also hindered clinical progression with its use. The use of stem cell therapy in the treatment of eye pathologies which is still undergoing clinical trials has shown to be a more viable treatment approach in ophthalmology as it targets retinal degenerative diseases thereby offering novel pathways for vision restoration. And also serves as a revolutionary alternative for treating severe ocular diseases. Stem cell delivery techniques might be quite cumbersome as the eye is a very delicate organ. The therapeutic interventional technique employed is aimed to ensure the reduction or absence of undesired effects in the deposition of the active pharmaceutical ingredient (API) being the stem cells. Techniques such as hydrogel-based injectables, which offer delivery of the APIs to the desired site of action without change in the physicochemical properties of the drug molecule, the scaffold delivery techniques, and the use of 3D bio-printing which can be used to develop scaffolds for retinal degeneration. The employment of artificial intelligence and machine learning in stem cell therapy has shown to be very fast and efficient in stem cell delivery and preventing likely human errors.

Unlike conventional treatments that often focus on managing symptoms, stem cells have the unique ability to repair and regenerate damaged tissues, addressing the root causes of the diseases. However, limitations due to economic, regulatory, and ethical challenges have posed barriers to advancing stem cell therapies.

The use of mesenchymal stem cells (MSCs) from perinatal tissue sources has gained attention due to their availability and lack of significant ethical or moral concerns. These cells have a higher proliferative capability than adult MSCs and less immunogenic or tumorigenesis risk than fetal and embryonic stem cells. Additionally, they do not require invasive isolation methods like fetal and adult MSCs. We reviewed the main biological and therapeutic aspects of perinatal MSCs in a three-part article. In the first part, we revised the main biological features and characteristics of MSCs and the advantages of perinatal MSCs over other types of SCs. In the second part, we provided a detailed molecular background for the main biomarkers that can be used to identify MSCs. In the final part, we appraised the therapeutic application of perinatal MSCs in four major degenerative disorders: degenerative disc disease, retinal degenerative diseases, ischemic heart disease, and neurodegenerative diseases. In conclusion, there is no single specific molecular marker to identify MSCs. We recommend using at least two positive markers of stemness (CD29, CD73, CD90, or CD105) and two negative markers (CD34, CD45, or CD14) to exclude the hematopoietic origin. Moreover, utilizing perinatal MSCs for managing degenerative diseases presents a promising therapeutic approach. This review emphasizes the significance of employing more specialized progenitor cells that originated from the perinatal MSCs. The review provides scientific evidence from the literature that applying these progenitor cells in therapeutic procedures provides a greater regenerative capacity than the original primitive MSCs. Finally, this review provides a valuable reference for researchers exploring perinatal MSCs and their therapeutic applications.

Ischemic reperfusion (IR) generates reactive oxygen species (ROS) that inevitably result in myocardial cell death and heart failure. The regenerative power of cardiac progenitor/stem pools (CSCs), especially the Sca1+ population, in response to IR injury remains unclear.

Our work sought to investigate whether small extracellular vesicles (sEVs) isolated from bone marrow-mesenchymal stem cells (BMMSCs) could rescue CSCs, specifically Sca-1+/CSCs, from IR by increasing their proliferative capacity and limiting their apoptosis in vitro. The Sca-1+/CSCs-IR model was induced by the oxygen-glucose deprivation/reoxygenation method (OGD/R). The effects of treatment with BMMSCs-derived sEVs on oxidative stress, cell proliferation, apoptosis, and cell cycle were assessed. To further test the mechanistic action, we assessed the PTEN/pAkt/HIF-1α pathway.

Compared to hypoxic untreated CSCs, BMMSCs-derived sEVs-treated cells had shifted from their quiescent to proliferative phase (p > 0.05) and showed decreased apoptosis (p < 0.001). sEVs-treated CSCs were predominately in the S phase (11.8 ± 0.9%) (p < 0.01). We identified an abundance of miRNA-21-5P in BMMSCs. HIF-1α expression was highest in CSCs treated with sEVs (p < 0.05). Moreover, miRNA-21-5p-rich sEVs shifted the redox state, reducing oxidative stress and promoting balance (p > 0.05).

Conditioning Sca-1+/CSCs, an essential population in the postnatal heart, with sEVs rich in miRNA-21 robustly enhanced the proliferation, and synthesis phase of the cell cycle, and stabilized HIF-1α while alleviating oxidative stress and apoptosis. Such sEVs rich in miRNA-21-5p can be further used as a preconditioning tool to enhance endogenous Sca-1+/CSCs regeneration in response to IR injury.

Cardiovascular diseases are a leading cause of morbidity and mortality in dogs, with limited options available for reversing myocardial damage. Stem cell therapies have shown significant potential for cardiac repair, owing to their immunomodulatory, antifibrotic, and regenerative properties. This review evaluates the therapeutic applications of mesenchymal stem cells (MSCs) derived from bone marrow, adipose tissue, and Wharton's jelly with a focus on their role in canine cardiology and their immunoregulatory properties. Preclinical studies have highlighted their efficacy in enhancing cardiac function, reducing fibrosis, and promoting angiogenesis. Various delivery methods, including intracoronary and intramyocardial injections, are assessed for their safety and efficacy. Challenges such as low cell retention, differentiation efficiency, and variability in therapeutic responses are also discussed. Emerging strategies, including genetic modifications and combination therapies, aim to enhance the efficacy of MSCs. Additionally, advances in delivery systems and regulatory frameworks are reviewed to support clinical translation. This comprehensive evaluation underscores the potential of stem cell therapies to revolutionize canine cardiovascular disease management while identifying critical areas for future research and clinical integration.

Knee osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disorder, which is particularly common in older population. While conventional treatments have limited effectiveness, the development of more effective therapeutic strategies is necessary to address this primary source of pain and disability. Umbilical cord mesenchymal stromal cells (UC-MSCs) offer a promising therapeutic approach for treating knee OA.

This randomized, prospective, double-blind and controlled pilot study was carried out to evaluate and compare the safety and therapeutic efficacy of a single intra-articular injection of a standardized product CellistemOA (5 × 106 ± 5 × 105 UC-MSCs), vs. triamcinolone (a synthetic corticosteroid) (10 mg/mL) in thirty patients with symptomatic knee OA (Kellgren-Lawrence grade II or III).

The outcomes included changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores based on a Likert scale, numerical rating score (NRS) for pain, Magnetic Resonance Imaging (MRI), and quality of life (SF-36 questionnaire), from baseline and throughout 12-months of follow-up.

Patients treated with CellistemOA showed significant improvement in WOMAC score (including the three subscale scores (pain, stiffness and function), NRS in pain, and SF-36 profile from baseline to 12 months (p < 0.05) compared to the triamcinolone group, and no severe adverse events were reported. There were no significant differences in MRI WORMS scores between the two groups. However, patients who received the cellular treatment experienced a significant improvement in their SF-36 profile (p < 0.05).

This pilot study revealed that a single dose of CellistemOA is safe and superior to the active comparator in knee OA at 1-year of follow-up, making it a compelling therapeutic alternative to treat symptomatic OA patients.

Human induced pluripotent stem cell derived hepatocytes (hiPSC-heps) hold promising value for acute liver failure (ALF) treatment, while their therapeutic efficacy is usually limited by low cell bioactivity and untargeted in vivo accumulation. Here, inspired by vascularity supporting cellular architectures in the tissues and organs, a novel vascularized hiPSC-heps spheroid based on microfluidic microcapsules is presented for liver repair via orthotopic transplantation. The microcapsules are comprised of aqueous cores that facilitate hiPSC-hep aggregating into spheroids, and hybrid hydrogel shells of sodium alginate and hyaluronic acid methacryloyl (HAMA). By selectively degrading the alginate, the microcapsules are imparted with porous HAMA shells, which not only allowed human umbilical vein endothelial cells (HUVECs) to attach and form vascularized networks, but also facilitated communication between HUVECs and hiPSC-heps. The specific spatial distributions of these cells in the vascularized hiPSC-hep spheroids can provide nutrition support, promote the hepatic functions, and avoid immune cell attacks. Based on these features, it is illustrated that the vascularized hiPSC-hep spheroids can repair the acute failing liver more effectively, indicating their practical values in clinical liver repair.

This study aimed to investigate the effects of super-activated platelet lysate (sPL) on the proliferation, migration, and chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs).

Cell proliferation and migration assay, enzyme-linked immunosorbent analysis, RT-qPCR, chondrogenic differentiation, and Western blot were performed on sPL-treated hUCMSCs.

The extraction of sPL from PRP yielded a significant release of growth factors. The proliferation of hUCMSCs was significantly enhanced by both 5% and 10% sPL, and the 5% sPL showed the most promising results. Additionally, 10% sPL demonstrated the strongest positive effect on hUCMSC migration. The 20% sPL group showed a significant decrease in inflammatory factor levels compared to the 0% sPL group when hIL-1β was added to the differentiation system. Notably, hUCMSCs in the 5% sPL, 10% sPL and 20% sPL groups displayed excellent chondrogenic differentiation.

In summary, sPL demonstrates the ability to promote stem cell proliferation, migration, and chondrogenic differentiation, while also suppressing inflammation.

Heart failure (HF) is a complex syndrome characterized by the reduced capacity of the heart to adequately fill or eject blood. Currently, HF remains a leading cause of morbidity and mortality worldwide, imposing a substantial burden on global healthcare systems. Recent advancements have highlighted the therapeutic potential of mesenchymal stromal cells (MSCs) in managing HF. Notably, umbilical cord-derived MSCs (UC-MSCs) have demonstrated superior clinical potential compared to traditional bone marrow-derived MSCs; this is evident in their non-invasive collection process, higher proliferation efficacy, and lower immunogenicity and tumorigenicity, as substantiated by preclinical studies. Although the feasibility and safety of UC-MSCs have been tested in animal models, the application of UC-MSCs in HF treatment remains challenged by issues such as inaccurate targeted migration and low survival rates of UC-MSCs. Therefore, further research and clinical trials are imperative to advance the clinical application of UC-MSCs.

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for OA treatment, achieving consistent clinical-grade sEV products remains a significant challenge. This study aims to develop fully characterized, reproducible, clinical-grade batches of sEV derived from umbilical cord (UC)-MSC for the treatment of OA while assessing its efficacy and safety. Initially, a standardized, research-grade manufacturing protocol was established to ensure consistent sEV production. UC-MSC-sEV characterization under non-cGMP conditions showed consistent miRNA and protein profiles, suggesting their potential for standardized manufacturing. In vitro studies evaluated the efficacy, safety, and potency of sEV; animal studies confirmed their effectiveness and safety. In vitro, UC-MSC-sEV polarized macrophages to an anti-inflammatory M2b-like phenotype, through STAT1 modulation, indicating their potential to create an anti-inflammatory environment in the affected joints. In silico studies confirmed sEV's immunosuppressive signature through miRNA and proteome analysis. In an OA mouse model, sEV injected intra-articularly (IA) induced hyaline cartilage regeneration, validated by histological and μCT analyses. The unique detection of sEV signals within the knee joint over time highlights its safety profile by confirming the retention of sEV in the joint. The product development of UC-MSC-sEV involved refining, standardizing, and validating processes in compliance with GMP standards. The initial assessment of the safety of the clinical-grade product via IA administration in a first-in-human study showed no adverse effects after a 12 month follow-up period. These results support the progress of this sEV-based therapy in an early-phase clinical trial, the details of which are presented and discussed in this work. This study provides data on using UC-MSC-sEV as local therapy for OA, highlighting their regenerative and anti-inflammatory properties and safety in preclinical and a proof-of-principle clinical application.

Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrine illness in women of reproductive age and is one of the most important causes of female infertility. The pathogenesis of PCOS is complex. Although mesenchymal stem cell therapy is anticipated to be a successful treatment for PCOS, its long-term safety, including tumorigenesis in patients, remains unknown.

This study aimed to confirm the efficacy and safety of human umbilical cord mesenchymal stem cells in improving fertility in PCOS mice.

In this study, dehydroepiandrosterone (DHEA) was used to construct a C56BL/6 mouse PCOS model, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used as a treatment, and the reproductive phenotype was observed in parallel breeding experiments to confirm the efficacy of the treatment. A 4-month follow-up period, final blood tests, and organ histology were carried out to confirm the long-term safety of the treatment.

After hUC-MSCs treatment, the sex hormone disorder of mice was corrected, the morphology and function of the ovary were improved, the number of offspring was significantly increased compared to the control group, and no adverse reactions related to stem cell transplantation such as tumor formation were found within 4 months.

The treatment of hUC-MSCs is safe and effective in treating PCOS over the long term.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by loss of the neurons, excessive accumulation of misfolded Aβ and Tau proteins, and degeneration of neural synapses, primarily occurring in the neocortex and the hippocampus regions of the brain. AD Progression is marked by cognitive deterioration, memory decline, disorientation, and loss of problem-solving skills, as well as language. Due to limited comprehension of the factors contributing to AD and its severity due to neuronal loss, even today, the medications approved by the U.S. Food and Drug Administration (FDA) are not precisely efficient and curative. Stem cells possess great potential in aiding AD due to their self-renewal, proliferation, and differentiation properties. Stem cell therapy can aid by replacing the lost neurons, enhancing neurogenesis, and providing an enriched environment to the pre-existing neural cells. Stem cell therapy has provided us with promising results in regard to the animal AD models, and even pre-clinical studies have shown rather positive results. Cell replacement therapies are potential curative means to treat AD, and there are a number of undergoing human clinical trials to make Stem Cell therapy accessible for AD patients. In this review, we aim to discuss the AD pathophysiology and varied stem cell types and their application.

Mesenchymal stem cells (MSCs) show significant promise in treating immune diseases due to their ability to differentiate into various cell types and their immunomodulatory properties. However, the mechanisms by which MSCs regulate CD4+T cells, essential for immune responses, are not yet fully understood. This study aims to provide a comprehensive overview of how MSCs and their secreted extracellular vesicles (EVs) modulate CD4+T cells in immune diseases. We begin by discussing the immunomodulatory properties of MSCs and the factors contributing to their effectiveness. Following this, we explore how MSCs interact with CD4+T cells through various pathways, including the secretion of soluble factors, direct cell-cell contact, and EV-mediated communication. A key focus is on the therapeutic potential of MSC-derived EVs, which are rich in bioactive molecules such as proteins, lipids, and nucleic acids. These molecules can regulate the phenotype and function of CD4+T cells. The challenges and future perspectives in utilizing MSCs and EVs for immune-disease therapy are also addressed. Overall, this research aims to enhance our understanding of the mechanisms behind MSC-mediated regulation of CD4+T cells and provide insights into the potential use of MSCs and EVs as therapeutic tools in immune diseases. In summary, understanding how MSCs and their EVs control CD4+T cells can offer valuable perspectives for developing innovative immunotherapeutic approaches. Leveraging the immunomodulatory capacity of MSCs and EVs holds promise for managing immune-related disorders.

Currently, no therapy is proven to effectively improve heart failure with preserved ejection fraction (HFpEF). Although stem cell therapy has demonstrated promising results in treating ischemic heart disease, the effectiveness of treating HFpEF with human umbilical cord mesenchymal stem cells (hucMSCs) remains unclear. To answer this question, we administered hucMSCs intravenously (i.v.), either once or repetitively, in a mouse model of HFpEF induced by a high-fat diet and NG-nitroarginine methyl ester hydrochloride. hucMSC treatment improved left ventricular diastolic dysfunction, reduced heart weight and pulmonary edema, and attenuated cardiac modeling (inflammation, interstitial fibrosis, and hypertrophy) in HFpEF mice. Repeat hucMSC administration had better outcomes than a single injection. In vitro, hucMSC culture supernatants reduced maladaptive remodeling in neonatal-rat cardiomyocytes. Ribonucleic acid sequencing and protein level analysis of left ventricle (LV) tissues suggested that hucMSCs activated the protein kinase B (Akt)/forkhead box protein O1 (FoxO1) signaling pathway to treat HFpEF. Inhibition of this pathway reversed the efficacy of hucMSC treatment. In conclusion, these findings indicated that hucMSCs could be a viable therapeutic option for HFpEF.

Biobanking has emerged as a transformative concept in advancing the medical field, particularly with the exponential growth of umbilical cord (UC) biobanking in recent decades. UC blood and tissue provide a rich source of primitive hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) for clinical transplantation, offering distinct advantages over alternative adult stem cell sources. However, to fully realize the therapeutic potential of UC-derived stem cells and establish a comprehensive global UC-biobanking network, it is imperative to optimize and standardize UC processing, cryopreservation methods, quality control protocols, and regulatory frameworks, alongside developing effective consent provisions. This review aims to comprehensively explore recent advancements in UC biobanking, focusing on the establishment of rigorous safety and quality control procedures, the standardization of biobanking operations, and the optimization and automation of UC processing and cryopreservation techniques. Additionally, the review examines the expanded clinical applications of UC stem cells, addresses the challenges associated with umbilical cord biobanking and UC-derived stem cell therapies, and discusses the promising role of artificial intelligence (AI) in enhancing various operational aspects of biobanking, streamlining data processing, and improving data analysis accuracy while ensuring compliance with safety and quality standards. By addressing these critical areas, this review seeks to provide insights into the future direction of UC biobanking and its potential to significantly impact regenerative medicine.

Articular cartilage damage is predominantly caused by trauma, osteoarthritis (OA), and other pathological conditions. The limited intrinsic capacity of cartilage tissue to self-repair necessitates timely intervention following acute injuries to prevent accelerated degeneration, leading to the development of planar arthritis or even osteoarthritis. Unfortunately, current therapies for articular cartilage damage are inadequate in effectively replacing or regenerating compromised cartilage due to the absence of suitable tissue-engineered artificial matrices. However, there is promise in utilizing hydrogels, a category of biomaterials characterized by their elasticity, smooth surfaces, and high water content, for cartilage regeneration. Recent advancements in hydrogel engineering have focused on improving their bioactive and physicochemical properties, encompassing innovative composition designs, dynamic modulation, and intricate architectures. This review provides a comprehensive analysis of hydrogels for articular cartilage repair, focusing on their innovative design, clinical applications, and future research directions. By integrating insights from the latest research studies and clinical trials, the review offers a unique perspective on the translation of hydrogels for articular cartilage repair, underscoring their potential as promising therapeutic agents.

This meta-analysis and systematic review compiles comparative data from 2004 to 2024, investigating the safety and efficacy of mesenchymal stem/stromal cells (MSCs) derived from various tissues for the treatment of ischemic cardiomyopathy (ICM) and associated heart failure. In addition, this review highlights the limitations of these interventions and provides valuable insights for future therapeutic approaches. Relevant articles were retrieved from the PubMed® database using targeted keywords. Our inclusion criteria included clinical trials with patients over 18 years of age, case reports and pilot studies. Animal experiments, in vitro studies, correlational and longitudinal studies, and study designs and protocols were excluded. Forty-nine original articles resulted in follow-up reports of 45 trials. MSCs from bone marrow, umbilical cord and adipose tissue were moderately well tolerated. Of the 1408 participants who received MSCs, 33 trials (67.3%) reported the occurrence of death or serious adverse events. These events resulted in 80 deaths (52% of reported cases) following MSC administration. Importantly, 41.3% of these deaths (n = 33) were not considered to be related to the intervention itself, while 40% of these deaths had no reported cause. As the primary outcome, the mean increase in left ventricular ejection fraction (LVEF) from baseline was 5.75% (95% CI: 3.38% -8.11%, p < 0.0001, I2 = 90,9%) in the randomized controlled trials only (n = 24) within the treatment groups and 3.19% (95% CI: 1.63% to 4.75%, p < 0.0001, I2 = 74,17%) in the control groups after the intervention. When the above results were compared using the standardized mean difference (SDM), a significance in favor of the treatment group was also found (SDM = 0.41; 95% CI: 0.19-0.64, p < 0.001, I2 = 71%). Although improvements were also seen in the control groups, 33.3% (n = 15) of the studies showed no significant difference between the control and treatment groups. The 6-minute walking test (6MWT) and New York Heart Association (NYHA) class scores, used for assessing exercise tolerance and quality of life (QoL), respectively, further supported the improvements in the treatment group. These improvements were noted as 62.5% (n = 10) for the 6MWT and 54.5% (n = 12) for the NYHA class scores. According to the risk of bias analysis, 4 trials were of good quality (11.8%), 15 were of fair quality (44.1%), and 15 were of poor quality (44.1%). Major limitations of these studies included small sample size, diagnostic challenges/lack, uncertain cell dosage and potential bias in patient selection. Despite the ongoing debate surrounding cell administration for ICM, there are supporting signs of improved clinical and laboratory outcomes, as well as improved QoL in the MSC-treated groups. However, it is important to recognize the limitations of each study, highlighting the need for larger, controlled trials to validate these findings.

The potential of biomaterials in medical sciences has attracted much interest, especially in promoting tissue regeneration and controlling immune responses. As the COVID-19 pandemic broke out, there was an increased interest in understanding more about how biomaterials could be employed to fight this dreaded disease, especially in the context of regenerative medicine. Out of the numerous regenerative medicine possibilities, stem cells and scaffolding (grafting) technology are two major areas in modern medicine and surgery. Mesenchymal stem cells are useful in tissue repair, tailored therapy and the treatment of COVID-19. Using biomaterials in COVID-19 treatment is intricate and needs multidisciplinary and cross-disciplinary research. Cell-based therapy and organ transplants pose immunological rejection challenges. Immunomodulation enhanced, tumorigenicity decreased, inflammation addressed and tissue damage restricted; bioengineered stem cells need clinical insights and validation. Advanced stem cell-based therapies should ideally be effective, safe and scalable. Cost and scalability shall dictate the dawn of techno-economically feasible regenerative medicine. A globally standard and uniform approval process could accelerate translational regenerative medicine. Researchers, patient advocacy organisations, regulators and biopharmaceutical stakeholders need to join hands for easy navigation of regulatory measures and expeditious market entry of regenerative medicine. This article summarises advances in biomaterials for regenerative medicine and their possible therapeutic benefits in managing infectious diseases like COVID-19. It highlights the significant recent developments in biomaterial design, scaffold construction, and stem cell-based therapies to treat tissue damage and COVID-19-linked immunological dysregulation. It also highlights the potential contribution of biomaterials towards creating novel treatment strategies to manage COVID-19.

Deep partial-thickness burns have a significant impact on both the physical and mental health of patients. Our previous study demonstrated human Umbilical Cord Mesenchymal stem cells (hUCMSCs) could enhance the healing of severe burns in small animal burn models, such as rats. Furthermore, our team has developed a deep partial-thickness burn model in Bama miniature pigs, which can be utilized for assessing drug efficacy in preclinical trials for wound healing. Therefore, this study further determine the optimal dosage of hUCMSCs in future clinical practice by comparing the efficacy of low-to-high doses of hUCMSCs on deep partial-thickness burn wounds in Bama miniature pigs.

The male Bama miniature pigs (N = 8, weight: 23-28 kg and length: 71-75 cm) were used to establish deep partial-thickness burn models, which used a continuous pressure of 1 kg and contact times of 35 s by the invented electronic burn instrument at 100℃ to prepare 10 round burn wounds with diameter of 5 cm according to our previous report. And then, 0 × 10^7, 1 × 10^7, 2 × 10^7, 5 × 10^7 and 1 × 10^8 doses of hUCMSCs were respectively injected into burn wounds of their corresponding groups. After treatment for 7, 14 and 21 days, the burned wound tissues were obtained for histological evaluation, including HE staining for histopathological changes, immunohistochemistry for neutrophil (MPO+) infiltration and microvessel (CD31+) quantity, as well as Masson staining for collagen deposition. The levels of inflammatory factors TNF-α, IL-1β, IL-10 and angiogenesis factors angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), as well as collagen type-I/type-III of the wound tissues were quantified by ELISA.

All of doses hUCMSCs can significantly increase wound healing rate and shorten healing time of the deep partial-thickness burn pigs in a dose-dependent manner. Furthermore, all of doses hUCMSCs can significantly promote epithelialization and decreased inflammatory reaction of wound, including infiltration of inflammatory cells and levels inflammatory factors. Meanwhile, the amounts of microvessel were increased in all of doses hUCMSCs group than those in the burn group. Furthermore, the collagen structure was disordered and partially necrotized, and ratios of collagen type-I and type-III were significantly decreased in burn group (4:1 in normal skin tissue), and those of all hUCMSCs groups were significantly improved in a dose-dependent manner. In a word, 1 × 10^8 dose of hUCMSCs could regenerate the deep partial-thickness burn wounds most efficaciously compared to other dosages groups and the burn group.

This regenerative cell therapy study using hUCMSCs demonstrates the best efficacy toward a high dose, that is dose of 1 × 10^8 of hUCMSCs was used as a reference therapeutic dose for treating 20 cm2 deep partial-thickness burns wound in future clinical practice.

The use of mesenchymal stem cells for heart failure treatment has gained increasing interest. However, most studies have relied on a single injection approach, with no research yet confirming the effects of multiple administrations. The present trial aims to investigate the safety and efficacy of multi-intravenous infusion of umbilical cord-mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF).

The PRIME-HFrEF trial is a single-center, prospective, randomized, triple-blinded, placebo-controlled trial of multi-intravenous infusion of UC-MSCs in HFrEF patients. A total of 40 patients meeting the inclusion criteria for HFrEF were enrolled and randomized 1:1 to the MSC group or the placebo group. Patients enrolled will receive intravenous injections of either UC-MSCs or placebo every 6 weeks for three times. Both groups will be followed up for 12 months. The primary safety endpoint is the incidence of serious adverse events. The primary efficacy endpoint is a change in left ventricular ejection fraction (LVEF) measured by left ventricular opacification (LVO) with contrast echocardiography and magnetic resonance imaging (MRI) at 12 months. The secondary endpoints include a composite of the incidence of death and re-hospitalization caused by heart failure at the 12th month, serum NT-proBNP, growth stimulation expressed gene 2 (ST2), and a change of right ventricular structure and function.

The PRIME-HFrEF study is designed to shed new light on multiple UC-MSC administration regimens for heart failure treatment.

The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes.

This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed.

A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches.

From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested.

Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis.

https://osf.io/th8yf/.

Myocardial infarction (MI) is a serious complication of coronary artery disease. This condition is common worldwide and has a profound impact on patients' lives and quality of life. Despite significant advances in the treatment of heart disease in modern medicine, the efficient treatment of MI still faces a number of challenges. Problems such as scar formation and loss of myocardial function after a heart attack still limit patients' recovery. Therefore, the search for a new therapeutic tool that can promote repair and regeneration of myocardial tissue has become crucial. In this context, mesenchymal stromal cells (MSCs) have attracted much attention as a potential therapeutic tool. MSCs are a class of adult stem cells with multidirectional differentiation potential, derived from bone marrow, fat, placenta and other tissues, and possessing properties such as self-renewal and immunomodulation. The application of MSCs may provide a new direction for the treatment of MI. These stem cells have the potential to differentiate into cardiomyocytes and vascular endothelial cells in damaged tissue and to repair and protect myocardial tissue through anti-inflammatory, anti-fibrotic and pro-neovascularization mechanisms. However, the clinical results of MSCs transplantation for the treatment of MI are less satisfactory due to the limitations of the native function of MSCs. Genetic modification has overcome problems such as the low survival rate of transplanted MSCs in vivo and enhanced their functions of promoting neovascularization and differentiation into cardiomyocytes, paving the way for them to become an effective tool for repair therapy after MI. In previous studies, MSCs have shown some therapeutic potential in experimental animals and preliminary clinical trials. This review aims to provide readers with a comprehensive and in-depth understanding to promote the wider application of engineering MSCs in the field of MI therapy, offering new hope for recovery and improved survival of cardiac patients.

Apoptosis, a form of programmed cell death, is critical for the development and homeostasis of the immune system. Chimeric antigen receptor T (CAR-T) cell therapy, approved for hematologic cancers, retains several limitations and challenges associated with ex vivo manipulation, including CAR T-cell susceptibility to apoptosis. Therefore, strategies to improve T-cell survival and persistence are required. Mesenchymal stem/stromal cells (MSCs) exhibit immunoregulatory and tissue-restoring potential. We have previously shown that the transfer of umbilical cord MSC (UC-MSC)-derived mitochondrial (MitoT) prompts the genetic reprogramming of CD3+ T cells towards a Treg cell lineage. The potency of T cells plays an important role in effective immunotherapy, underscoring the need for improving their metabolic fitness. In the present work, we evaluate the effect of MitoT on apoptotis of native T lymphocytes and engineered CAR-T cells.

We used a cell-free approach using artificial MitoT (Mitoception) of UC-MSC derived MT to peripheral blood mononuclear cells (PBMCs) followed by RNA-seq analysis of CD3+ MitoTpos and MitoTneg sorted cells. Target cell apoptosis was induced with Staurosporine (STS), and cell viability was evaluated with Annexin V/7AAD and TUNEL assays. Changes in apoptotic regulators were assessed by flow cytometry, western blot, and qRT-PCR. The effect of MitoT on 19BBz CAR T-cell apoptosis in response to electroporation with a non-viral transposon-based vector was assessed with Annexin V/7AAD.

Gene expression related to apoptosis, cell death and/or responses to different stimuli was modified in CD3+ T cells after Mitoception. CD3+MitoTpos cells were resistant to STS-induced apoptosis compared to MitoTneg cells, showing a decreased percentage in apoptotic T cells as well as in TUNEL+ cells. Additionally, MitoT prevented the STS-induced collapse of the mitochondrial membrane potential (MMP) levels, decreased caspase-3 cleavage, increased BCL2 transcript levels and BCL-2-related BARD1 expression in FACS-sorted CD3+ T cells. Furthermore, UC-MSC-derived MitoT reduced both early and late apoptosis in CAR-T cells following electroporation, and exhibited an increasing trend in cytotoxic activity levels.

Artificial MitoT prevents STS-induced apoptosis of human CD3+ T cells by interfering with the caspase pathway. Furthermore, we observed that MitoT confers protection to apoptosis induced by electroporation in MitoTpos CAR T-engineered cells, potentially improving their metabolic fitness and resistance to environmental stress. These results widen the physiological perspective of organelle-based therapies in immune conditions while offering potential avenues to enhance CAR-T treatment outcomes where their viability is compromised.

During a heart attack, ischemia causes losses of billions of cells; this is especially concerning given the minimal regenerative capability of cardiomyocytes (CMs). Heart remuscularization utilizing stem cells has improved cardiac outcomes despite little cell engraftment, thereby shifting focus to cell-free therapies. Consequently, we chose induced pluripotent stem cells (iPSCs) given their pluripotent nature, efficacy in previous studies, and easy obtainability from minimally invasive techniques. Nonetheless, using iPSC secretome-based therapies for treating injured CMs in a clinical setting is ill-understood. We hypothesized that the iPSC secretome, regardless of donor health, would improve cardiovascular outcomes in the CM model of ischemia-reperfusion (IR) injury. Episomal-generated iPSCs from healthy and dilated cardiomyopathy (DCM) donors, passaged 6-10 times, underwent 24 h incubation in serum-free media. Protein content of the secretome was analyzed by mass spectroscopy and used to treat AC16 immortalized CMs during 5 h reperfusion following 24 h of hypoxia. IPSC-derived secretome content, independent of donor health status, had elevated expression of proteins involved in cell survival pathways. In IR conditions, iPSC-derived secretome increased cell survival as measured by metabolic activity (p < 0.05), cell viability (p < 0.001), and maladaptive cellular remodelling (p = 0.052). Healthy donor-derived secretome contained increased expression of proteins related to calcium contractility compared to DCM donors. Congruently, only healthy donor-derived secretomes improved CM intracellular calcium concentrations (p < 0.01). Heretofore, secretome studies mainly investigated differences relating to cell type rather than donor health. Our work suggests that healthy donors provide more efficacious iPSC-derived secretome compared to DCM donors in the context of IR injury in human CMs. These findings illustrate that the regenerative potential of the iPSC secretome varies due to donor-specific differences.

Mesenchymal stromal/stem cells (MSC) have emerged as a promising therapeutic avenue for treating autoimmune diseases, eliciting considerable interest and discussion regarding their underlying mechanisms. This study revealed the distinctive ability of human umbilical cord MSC to aggregate within the lymph nodes of mice afflicted with autoimmune diseases, but this phenomenon was not observed in healthy mice. The specific distribution is driven by the heightened expression of the CCL21-CCR7 axis in mice with autoimmune diseases, facilitating the targeted homing of MSC to the lymph nodes. Within the lymph nodes, MSC exhibit a remarkable capacity to modulate Th17 cell function, exerting a pronounced anti-inflammatory effect. Transplanted MSC stimulates the secretion of L-amino-acid oxidase (LAAO), a response triggered by elevated levels of tumor necrosis factor-α (TNF-α) in mice with autoimmune diseases through the NF-κB pathway. The presence of LAAO is indispensable for the efficacy of MSC, as it significantly contributes to the inhibition of Th17 cells. Furthermore, LAAO-derived indole-3-pyruvic acid (I3P) serves as a potent suppressor of Th17 cells by activating the aryl hydrocarbon receptor (AHR) pathway. These findings advance our understanding of the global immunomodulatory effects exerted by MSC, providing valuable information for optimizing therapeutic outcomes.

Cell therapy using adipose-derived mesenchymal stem cells (ADSCs) shows great potential as a treatment for cardiovascular diseases.

We conducted a systematic review to describe the safety and efficacy of ADSCs in ischemic heart disease.

We searched PubMed/MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS (from inception to March 2024) for clinical studies involving ADSCs in patients with ischemic heart disease. We excluded studies involving patients with other types of heart disease, studies using mesenchymal stem cells derived from other tissues, as well as ongoing studies. Two independent reviewers screened the retrieved citations, extracted relevant data, and assessed the risk of bias in the included trials, using the Cochrane Collaboration criteria modified by McMaster University and Methodological Index for Non-Randomized Studies (MINORS). We used a narrative synthesis to present the results.

Ten studies (comprising 29 publications) met our inclusion criteria, including 8 randomized controlled trials and 2 uncontrolled trials. No severe adverse events associated with ADSC therapy were reported. While most efficacy endpoints did not reach statistical significance, there were reports of improved ischemic area, functional capacity, symptoms, and contractility in patients treated with ADSCs.

The findings from our review suggest that ADSC therapy is generally safe for patients with ischemic heart disease. However, further investigation is warranted to confirm its efficacy, particularly with larger clinical trials and in specific conditions where improvements in microcirculation may have a notable impact on clinical outcomes.

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies.