In clinical trials, mesenchymal stromal/stem cells (MSCs) have consistently demonstrated safety. However, demonstration of efficacy has been inconsistent and many MSC trials have failed to meet their efficacy endpoint. This disappointing reality is reflected by the limited number MSC therapies approved by regulatory agencies, despite the large number of MSC trials registered on clinicaltrials.gov. Notably, there has been a recent approval of an MSC therapy for pediatric graft-vs.-host disease in the United States, marking the first MSC therapy approved by the U.S. Food and Drug Administration. This review provides a background of the history and potential therapeutic value of MSCs, an overview of MSC products with regulatory approval, and a summary of registered MSC trials. It concludes with a discussion on current and ongoing challenges and questions surrounding MSC therapy that remains to be resolved before becoming available for routine clinical use outside of clinical trials.

Stem cell-based therapies have emerged as a promising frontier in the treatment of gastrointestinal disorders, offering potential solutions for challenges posed by conventional treatments. This review comprehensively examines recent advancements in cell-based therapeutic strategies, particularly focusing on stem cell applications, immunotherapy, and cellular therapies for digestive diseases. It highlights the successful differentiation of enteric neural progenitors from pluripotent stem cells and their application in animal models, such as Hirschsprung disease. Furthermore, the review evaluates clinical trials and experimental studies demonstrating the potential of stem cells in regenerating damaged tissues, modulating immune responses, and promoting healing in conditions like Crohn's disease and liver failure. By addressing challenges, such as scalability, immunogenicity, and ethical considerations, the review underscores the translational opportunities and obstacles in realizing the clinical potential of these therapies. Concluding with an emphasis on future directions, the study provides insights into optimizing therapeutic efficacy and fostering innovations in personalized medicine for digestive disorders.

There is limited long-term clinical outcome data supporting the use of cell-based therapy to treat heart failure. The HYPERION study (NCT03071835) followed long-term outcomes of patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NIDCM) who received mesenchymal stromal cells (MSC). We hypothesized that improved cardiac parameters predict longer event-free survival.

We performed a Kaplan-Meier analysis to examine event-free survival as the primary outcome. Time-to-event information was captured from all eligible participants. Endpoint events were defined as death (all-cause), Left Ventricular Assist Device (LVAD) placement, or Heart Transplant. Subjects were categorized based on increase in Left Ventricular Ejection Fraction (LVEF) or decrease in Left Ventricular End Diastolic Volume (LVEDV) for comparisons within disease etiologies.

There were 134 men and 21 women, with mean age 60.0 ± 11.0 years. There were 121 (78%) with ICM and 34 (22%) with NIDCM. By the end of long-term follow-up (~13 years), 38 (24.5%) subjects had deceased, 5 (3.2%) received LVAD, and 8 (5.2%) underwent heart transplantation. Post-therapy increase of ≥5% LVEF was associated with longer event-free survival in NIDCM (HR:0.31; 95%CI, 0.11,0.86; P = .025), but not ICM (HR:1.14; 95%CI, 0.47,2.72; P = .776). Conversely, reduction in left ventricular end-diastolic volume (LVEDV) was associated with longer event-free survival in ICM (HR:0.16; 95%CI, 0.05, 0.55; P = .008) but not NIDCM (HR:0.35; 95%CI, 0.1,1.2; P = .098). ICM improvers had LVEDV of 225.7 ± 95.9 mL at baseline and 209.0 ± 100.6 mL by year 5 (P = .046). NIDCM improvers had LVEF of 27.2 ± 8.9% at baseline and 36.1 ± 11.6% by year 5 (P = .018).

In this long-term observational cohort analysis, improvement of LVEF and/or reduction in LVEDV was associated with survival benefits among subjects with NIDCM and ICM, respectively. In both etiologies the respective improvements are sustained for up to 5 years, providing evidence that cell-based therapy may be a promising and durable treatment option for patients with heart failure.

Steroid-refractory acute Graft-versus-Host Disease (SR-aGVHD) is a potentially fatal complication occurring in approximately 60-70% of severe grade III-IV GVHD cases, with a higher incidence in patients with gastrointestinal (GI) involvement. GI aGVHD is associated with poor prognosis, with a 2-year overall survival (OS) rate of only 25% in patients with stage 3-4 GI involvement. Mesenchymal stromal cells (MSC) have emerged as a promising therapeutic option due to their favorable efficacy and safety profile. However, data on bone marrow (BM)-derived MSC use in biopsy-proven grade III-IV SR-aGVHD with GI involvement, particularly in stage 3-4 cases, remain limited.

This prospective, observational, single-arm, single-center study assessed the efficacy and safety of BM-derived MSC for treating adult patients with biopsy-proven grade III-IV SR-aGVHD with predominant GI involvement. Early (1st-2nd) passage BM-derived MSC were administered weekly at a target dose of 1x106 MSC/kg in two regimens: up to three (MSC3) and six doses (MSC6).

Fifty-seven adult patients with biopsy-proven III-IV grade SR-aGVHD (93% with GI involvement) received MSC treatment. The overall response rate (ORR) was 39% and 42% on Days 14 and 28, respectively, with no significant differences between the two MSC groups (Day 28 ORR 38% for MSC3 and 44% for MSC6). In patients with stage 3-4 GI involvement, the ORR was 26% and 36% at the corresponding time points with comparable efficacy between the two MSC groups (Day 28 ORR 31% for MSC3 and 38% for MSC6). Day 14 and Day 28 responders had significantly higher OS compared to non-responders (52% vs. 7%, p=0.000; 54% vs. 5%, p=0.000), with a comparable OS benefit observed in patients with stage 3-4 GI involvement (45% vs. 8%, p=0.005; 42% vs. 6%, p=0.005), respectively. MSC treatment had a favorable safety profile. The one, 5 and 10-year OS rates were 27%, 24%, and 24%, respectively.

The grade III-IV SR-aGVHD patients, including cases with biopsy-proven severe GI involvement, had significantly better clinical outcomes if responses to MSC treatment were observed on Days 14 and 28. Intensified MSC administration schedule has failed to improve the clinical outcomes. MSC studies focusing on aGVHD prevention and (or) first-line treatment in combination with other agents should be considered.

Mesenchymal stromal cells (MSCs) have been under clinical investigation for the treatment of cerebral palsy (CP) for over a decade. However, the field has been limited by study heterogeneity and variable reports of efficacy. We conducted a scoping review of published and registered reports of MSC treatment for CP, with meta-analysis of Gross Motor Function Measure (GMFM) outcomes to summarize research and provide future recommendations. Thirty published reports and 10 registered trials were identified, including 1292 people with CP receiving MSCs. Most received ≥2 doses (72%) of umbilical cord tissue MSCs (75%), intrathecally (40%) or intravenously (38%), and 31% were treated via compassionate/Expanded access. MSC treatment was safe and meta-analyses demonstrated that MSCs conferred significant improvements in GMFM at 3 - (1.05 (0.19-1.92), p = 0.02), 6 - (0.97 (0.30-1.64), p = 0.005) and 12 months (0.99 (0.30-1.67), p = 0.005) post-treatment. Whilst MSCs are safe and improve GMFM outcomes in CP with large effect sizes, study and participant variability continues to confound data interpretation and limits subgroup analyses. With no published Phase 3 trials and high rates of compassionate access, the field would benefit from well-designed trials with unified outcomes. Additionally, data sharing to enable Individual Participant Data Meta-Analysis would support the determination of optimal source, route and dose to progress towards regulatory approval.

Steroid-refractory acute graft-versus-host disease (SR-AGVHD) presents a significant barrier to successful outcomes following allogeneic hematopoietic cell transplantation (HCT), despite advancements in GVHD prophylaxis and management. While ruxolitinib therapy has shown improved response rates, survival benefits remain elusive. This review explores the definitions and proposed distinct pathophysiology and treatment landscape of SR-AGVHD. Emerging therapies offer potential, yet further research is critical to better define steroid-refractory populations, improve treatment precision with biomarkers, and overcome resistance, particularly in ruxolitinib-refractory cases.

Defining the mechanism of immune modulation by mesenchymal stromal cells (MSCs) from distinct anatomical tissues is of great translational interest. The human cornea is an immunologically privileged organ, and the mechanism of immunoregulation of cornea-derived MSCs (cMSCs) is currently unknown. We investigated cMSCs derived from the corneas of 5 independent human donorS for their fitness and mechanism of action in suppressing T cells. cMSCs display the immunophenotype CD45-CD73+CD105+CD90+CD44+ and robust in vitro growth. 30-plex secretome analysis identified that cMSCs innately secrete specific molecules in a dose-dependent manner. cMSCs do not express or upregulate costimulatory but do upregulate coinhibitory molecules upon stimulation with interferon γ (IFNγ). cMSCs inhibit T-cell proliferation in contact-dependent co-cultures, which can be predicted by a unique secretome signature. In addition, co-culturing in a 2-chamber transwell system has demonstrated that cMSCs also inhibit T-cell proliferation in a non-contact-dependent manner. Mechanistic analysis has demonstrated that activated T cells effectively induce indoleamine 2,3-dioxygenase (IDO) but not other enzymes of the tryptophan metabolic pathway in cMSCs. Silencing of IDO in cMSCs reduces their fitness to suppress T cells. These results provide evidence that in cMSCs, one of the principal mechanisms of immunosuppression on T cells is through IDO. These results suggest that MSCs derived from the human cornea display immunoregulatory properties and, thus, may play a role in maintaining the immune-privileged niche of the cornea.

Retinal degeneration, characterized by the progressive loss of photoreceptors, retinal pigment epithelium cells, and/or ganglion cells, is a leading cause of vision impairment. These diseases are generally classified as inherited (e.g., retinitis pigmentosa, Stargardt disease) or acquired (e.g., age-related macular degeneration, diabetic retinopathy, glaucoma) ocular disorders that can lead to blindness. Available treatment options focus on managing symptoms or slowing disease progression and do not address the underlying causes of these diseases. However, recent advancements in regenerative medicine offer alternative solutions for repairing or protecting degenerated retinal tissue. Stem and progenitor cell therapies have shown great potential to differentiate into various retinal cell types and can be combined with gene editing, extracellular vesicles and exosomes, and bioactive molecules to modulate degenerative cellular pathways. Additionally, gene therapy and neuroprotective molecules play a crucial role in enhancing the efficacy of regenerative approaches. These innovative strategies hold the potential to halt the progression of retinal degenerative disorders, repair or replace damaged cells, and improve visual function, ultimately leading to a better quality of life for those affected.

Traumatic or degenerative defects of articular cartilage impair joint function, and the treatment of articular cartilage damage remains a challenge. By mimicking the cartilage extracellular matrix (ECM), exosome-seeded cryogels may enhance cell proliferation and chondral repair. ECM-based cryogels were cryopolymerized with gelatin, chondroitin sulfate, and various concentrations (0%, 0.3%, 0.5%, and 1%) of hyaluronic acid (HA), and their water content, swelling ratio, porosity, mechanical properties, and effects on cell viability were evaluated. The regenerative effects of bone marrow-derived mesenchymal stem cell (BM-MSC)-derived exosome (at a concentration of 106 particles/mL)-seeded 0.3% HA cryogels were assessed in vitro and in surgically induced male New Zealand rabbit cartilage defects in vivo. The water content, swelling ratio, and porosity of the cryogels significantly (p < 0.05) increased and the Young's modulus values of the cryogels decreased with increasing HA concentrations. MTT assays revealed that the developed biomaterials had no cytotoxic effects. The optimal cryogel composition was 0.3% HA, and the resulting cryogel had favorable properties and suitable mechanical strength. Exosomes alone and exosome-seeded cryogels promoted chondrocyte proliferation (with cell optical densities that were 58% and 51% greater than that of the control). The cryogel alone and the exosome-seeded cryogel facilitated ECM deposition and sulfated glycosaminoglycan synthesis. Although we observed cartilage repair via Alcian blue staining with both the cryogel alone and the exosome-seeded cryogel, the layered arrangement of the chondrocytes was superior to that of the control chondrocytes when exosome-seeded cryogels were used. This study revealed the potential value of using BM-MSC-derived exosome-seeded ECM-based cryogels for cartilage tissue engineering to treat cartilage injury.

Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE.

This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the Saint-Louis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 × 106, 2 × 106, or 4 × 106 umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 × 106 cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade ≥3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29.

From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 × 106 dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 × 106 cells per kg (range 2 × 106 to 4 × 106). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12·4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse.

Our results suggest that a single infusion of 2 × 106 cells per kg or 4 × 106 cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to confirm clinical efficacy and the role of B-cell modifications in clinical benefit.

Fondation du Rein, Alliance Maladies Rares AFM-Téléthon, Direction de la Recherche Clinique et de l'Innovation AP-HP, and ANR eCellFrance.

Periodontitis, the main cause of tooth loss in adults, is a public health concern; its incidence increases with age, and its prevalence increases with increasing life expectancy of the population. Innovative therapies such as cell therapy represent promising future solutions for guided tissue regeneration. However, these therapies may be associated with fears and mistrust from the general public. The aim of this study was to estimate the acceptability of an advanced therapy medicinal product combining allogeneic mesenchymal stromal cells from adipose tissue with a natural fibrin hydrogel in the treatment of periodontitis.

The methodology was based on a qualitative study conducted through semi-structured interviews with patients followed for periodontitis in the Oral Medicine Department of the Toulouse University Hospital, Toulouse, France. Qualitative studies are essential methodologies to understand the patterns of health behaviours, describe illness experiences, and design health interventions in a humanistic and person-centred way of discovering.

Eleven interviews (with 4 men and 7 women) were required to reach thematic saturation. Analysis allowed 4 main themes to emerge: (1) perception of new treatments, science, and caregivers; (2) conditions that the treatment must meet; (3) patient perception of the disease; and (4) factors related to the content of the treatment.

Patients find cell therapy for periodontitis to be acceptable. If they express a need to be informed about the benefit/risk ratio, they are not particularly worried about side effects of the treatment, for either allogeneic or blood-derived products. Periodontitis is a prototypical model of chronic inflammatory pathology and is multitissular, with hard- and soft-tissue lesions. In a patient-centred approach, the success of cell therapy will require a bilateral, informed decision, taking into account potential therapeutic effectiveness and patient expectations for regeneration.

Mesenchymal stem cells (MSCs) have emerged as a relevant strategy in regenerative medicine due to their multipotent differentiation capacity, immunomodulatory properties, and therapeutic applications in various medical fields. This review explores the therapeutic use of MSCs, focusing on their role in treating autoimmune disorders and neoplastic diseases and in tissue regeneration. We discuss the mechanisms underlying MSC-mediated tissue repair, including their paracrine activity, migration to injury sites, and interaction with the immune system. Advances in cellular therapies such as genome engineering and MSC-derived exosome treatments further enhance their applicability. Key methodologies analyzed include genomic studies, next-generation sequencing (NGS), and bioinformatics approaches to optimize MSC-based interventions. Additionally, we reviewed preclinical and clinical evidence demonstrating the therapeutic potential of MSCs in conditions such as graft-versus-host disease, osteoarthritis, liver cirrhosis, and neurodegenerative disorders. While promising, challenges remain regarding standardization, long-term safety, and potential tumorigenic risks associated with MSC therapy. Future research should focus on refining MSC-based treatments to enhance efficacy and minimize risks. This review underscores the need for large-scale clinical trials to validate MSC-based interventions and fully harness their therapeutic potential.

Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for nine months after a single dose of only 1500 magnetically-steered hAMSCs, explained by increased outflow through the conventional pathway and associated with an higher TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle three weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically-steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma.

A novel magnetic cell therapy provided effective intraocular pressure reduction in a mouse model, motivating future translational studies.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β cells within pancreatic islets, the specialized endocrine cell clusters of the pancreas. Islet transplantation has emerged as a β cell replacement therapy, involving the infusion of cadaveric islets into a patient's liver through the portal vein. This procedure offers individuals with T1D the potential to restore glucose control, reducing or even eliminating the need for exogenous insulin therapy. However, it does not address the underlying autoimmune condition responsible for T1D. The need for systemic immunosuppression remains the primary barrier to making islet transplantation a more widespread therapy for patients with T1D. Here, we review recent progress in addressing the key limitations of islet transplantation as a viable treatment for T1D. Concerns over systemic immunosuppression arise from its potential to cause severe side effects, including opportunistic infections, malignancies, and toxicity to transplanted islets. Recognizing the risks, the Edmonton protocol (2000) marked a shift away from glucocorticoids to prevent β cell damage specifically. This transition led to the development of combination immunosuppressive therapies and the emergence of less toxic immunosuppressive and anti-inflammatory drugs. More recent advances in islet transplantation derive from islet encapsulation devices, biomaterial platforms releasing immunomodulatory compounds or surface-modified with immune regulating ligands, islet engineering and co-transplantation with accessory cells. While most of the highlighted studies in this review remain at the preclinical stage using mouse and non-human primate models, they hold significant potential for clinical translation if a transdisciplinary research approach is prioritized.

Interest in Current Good Manufacturing Practices (cGMP)-grade extracellular vesicles (EVs) is expanding. Some obstacles in this new but rapidly growing field include a lack of standardization and scalability. This review focuses on automated biomanufacturing of EVs in conditioned media collected from cultured mesenchymal stromal cells (MSCs). Different automated cell culture systems are discussed, including factors affecting EV quantity and quality, isolating EVs manufactured in an automated system, and validations needed. The ultimate goal when manufacturing cGMP-grade EVs is to identify a specific application and characterize the EV population in detail. This is achieved by validating every step of the process, choosing appropriate release criteria, and assuring batch-to-batch consistency. Due to the lack of standards in the field, it is critical to ensure that the cGMP-grade EVs meet FDA standards pertaining to identity, reproducibility, sterility, safety, purity, and potency. A closed-system automated bioreactor can be a valuable tool to generate cGMP-EVs in a scalable, economical, and reproducible manner.

This meta-analysis aimed to pool the existing evidence to determine the clinical efficacy and safety of mesenchymal stem cells (MSC) in patients with non-unions.

A systematic search in PubMed and Scopus was performed until October 2024 to gather pertinent studies. The inclusion criteria included participants with non-unions, the intervention of MSC administration, a comparator of standard treatment (bone graft), and outcomes focused on healing rate, healing time, or side effects. The Jadad score Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in randomized and non-randomized studies, respectively. Moreover, GRADE criteria were used to assess the quality of evidence. Using a random effects model, odds ratios (OR) with 95% confidence intervals (CIs) were calculated for healing and complication rates, while standardized mean differences (SMD) with their 95% CIs were used to assess the impact of MSC therapy on bone union time.

Twenty-one studies, with 866 patients, were included. The bone healing rates were 44% at 3 months, 73% at 6 months, 90% at 9 months, and 86% at 12 months, eventually reaching 91% after 12 months of follow-up. MSC therapy, with or without scaffolds, was linked to higher odds of bone healing rate at 3 and 6 months, compared to bone grafts as the standard care (OR = 1.69). The time to union following the treatment was 6.30 months (95%CI: 86-96%), with patients treated with MSC/Scaffold experiencing a shorter time compared to MSC alone (5.85 vs. 6.36 months). MSC therapy significantly decreased bone union time (SMD:-0.54 months, 95% CI: -0.75 to -0.33). The complication rate was 1% (MSC/Scaffold: 0%, MSC alone: 2%), with MSC alone or MSC/Scaffold showing a lower risk than the standard care (OR = 0.41, 95% CI: 0.22-0.78).

MSC is a potential adjunct therapy for patients with non-union fractures.

Not applicable.

The long-term effect of adipose-derived mesenchymal stromal cells (ASC) on restoring radiation-induced salivary gland hypofunction in patients with previous head and neck cancer has not been validated in larger settings.

The study was a 12-month follow-up of a randomized trial, including patients with hyposalivation. Patients were randomized to receive allogeneic ASC or placebo in the submandibular glands. The primary endpoint was unstimulated whole saliva (UWS) followed by stimulated whole saliva, patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Module, and the xerostomia questionnaire), and safety.

Of the 120 enrolled patients, 117 (97.5%) were assessed at 12 months. Treatment with ASC did not increase UWS compared with placebo: Increase in UWS was 0.02 mL/minute [95% confidence interval (CI), 0.01-0.04] in the ASC group and 0.02 mL/minute (95% CI, 0-0.03) in the placebo group (P = 0.56). ASC reduced the symptom burden for dry mouth with -10.07 units (95% CI, -13.39 to -6.75) compared with -4.15 units (95% CI, -7.46 to -0.84) in the placebo group (P = 0.01). Compared with placebo, ASC did not improve sticky saliva (-9.27 vs. -4.55 units; P = 0.13), swallowing (-4.50 vs. 3.49 units; P = 0.5), or xerostomia (-3.12 vs. -2.74 units; P = 0.82). Treatment was safe and associated with a transient immune response.

Intraglandular ACS therapy in the submandibular glands significantly relieved subjective dry mouth symptoms. Both ASC and placebo increased UWS, but ASC did not prove superior to placebo in restoring salivary gland function, based on the salivary flow rate.

In recent years, the landscape of hematology has undergone rapid transformation, driven by innovative therapeutic strategies harnessing the properties of novel cellular therapies. Mesenchymal stem cells (MSCs) represent one of these promising therapies, with potential applications across a range of hematologic conditions. These cells are notable for their immunomodulatory properties, key role in supporting the hematopoietic micro-environment and capacity for multi-directional differentiation. This review will focus on the biologic mechanisms underlying MSC therapeutic use, current avenues of clinical investigation, and potential challenges and future directions for MSC derived therapies.

Stress urinary incontinence (SUI) is a prevalent pelvic floor dysfunction in women post-pregnancy. Currently, conservative treatment options have low success rates, while surgical interventions often result in multiple complications. The altered state of the extracellular matrix (ECM) is a pivotal factor in the onset of various diseases and likely plays a significant role in the pathogenesis of SUI, particularly through changes in collagen and elastin levels. Recent advances in mesenchymal stem cells (MSCs) therapy have shown considerable promise in treating SUI by modulating ECM remodeling, thereby enhancing the supportive tissues of the female pelvic floor. MSCs exhibit substantial potential in enhancing urethral sphincter function, modulating connective tissue architecture, and stimulating fibroblast activity. They play a pivotal role in the reconstruction and functional recovery of the ECM by influencing various signaling pathways, including TGF-β/SMAD, JAK/STAT, Wnt/β-catenin, PI3K/AKT, and ERK/MAPK. We have reviewed the advancements in MSC-mediated ECM metabolism in SUI and, by integrating the functions of ECM in other diseases and how MSCs can ameliorate conditions through their impact on ECM metabolism, we have projected the future trajectory of SUI treatment development.

Mesenchymal stem cells (MSCs) have emerged as a promising tool for regenerative medicine due to their multipotency and immunomodulatory properties. According to recent research, exposing MSCs to super-low-intensity microwave radiation can have a significant impact on how they behave and operate. This review provides an overview of the most recent studies on the effects of microwave radiation on MSCs with power densities that are much below thermal values. Studies repeatedly show that non-thermal mechanisms affecting calcium signaling, membrane transport, mitochondrial activity, along ion channel activation may increase MSC proliferation, differentiation along mesodermal lineages, paracrine factor secretion, and immunomodulatory capabilities during brief, regulated microwave exposures. These bioeffects greatly enhance MSC regeneration capability in preclinical models of myocardial infarction, osteoarthritis, brain damage, and other diseases. Additional study to understand microwave treatment settings, biological processes, and safety assessments will aid in the translation of this unique, non-invasive strategy of activating MSCs with microwave radiation to improve cell engraftment, survival, and tissue healing results. Microwave-enhanced MSC treatment, if shown safe and successful, might have broad relevance as a novel cell-based approach for a variety of regenerative medicine applications.

To visualize and analyze the trends and hotspots of efferocytosis and inflammation via bibliometric methods.

Relevant articles and reviews from 2006 to 2023 were retrieved from the Web of Science Core Collection. The data were processed with CiteSpace, and some graphs were generated with Microsoft Excel (version 2016), VOSviewer, Scimago Graphica, Bibliometrix and R Studio.

A total of 1,003 papers were included, revealing a significant upward trend in efferocytosis and inflammation research. The United States (456, 45.46%), China (164, 16.35%) and the United Kingdom (99, 9.87%) were the three countries with the highest numbers of publications. Harvard University (84, 6.74%) contributes the most out of the top 5 institutions. Among the researchers in this field, Serhan CN was the author with the highest number of articles in the field (35, 3.49%), and deCathelineau AM first named "efferocytosis" in 2003. Keyword analysis identified "activation," "tam receptors," "docosahexaenoic acid" "systemic lupus erythematosus," "myocardial infarction" and "alveolar macrophages" as core topics, indicating a concentrated trend in the mechanism of physiological state and inflammatory diseases such as autoimmune, cardiovascular, and pulmonary diseases. The latest surge words "inflammation resolution" and "cancer" in the keyword heatmap indicate future research directions.

Research on the association between efferocytosis and inflammation has been a promising field. Key areas of focus include the crucial role of efferocytosis on tissue homeostasis and the pathogenesis of nontumorous inflammatory diseases. Future research will likely continue to explore these frontiers, with an emphasis on understanding efferocytosis in the context of chronic diseases and cancer, as well as developing novel therapeutic strategies.

Postmenopausal osteoporosis is a common degenerative disease, with suboptimal clinical outcomes. The targets of current therapeutic agents are both nonspecific and diverse. We synthesized a novel nanoparticle (NP), ALN@BMSCM@PLGA-TK-PEG-SS31. After intravenous injection, the NP evaded immune phagocytosis, targeted bone tissue, and efficiently downregulated bone reactive oxygen species (ROS) generation. The core PLGA-TK-PEG-SS31 NP was ∼100 nm in diameter. The TK chemical bond breaks on exposure to ROS, releasing the novel mitochondrion-targeting peptide SS31. Outer bone marrow mesenchymal stem cell membranes (BMSCMs) were used to coat the NP with surface proteins to ensure membrane functionality. The circulation time was prolonged and immune phagocytosis was evaded. Embedding the DSPE-PEG-ALN lipid within the cell membrane enhanced the bone-targeting ability of the NP. Our results suggest that ALN@BMSCM@PLGA-TK-PEG-SS31 exerted dual effects on bone tissue in vitro, significantly inhibiting RANKL-induced osteoclastogenesis in the presence of H2O2 and promoting osteogenic differentiation in BMSCs. In a mouse model of ovariectomy-induced osteoporosis, ALN@BMSCM@PLGA-TK-PEG-SS31 significantly ameliorated oxidative stress and increased bone mass with no notable systemic side effects. These results suggest that ALN@BMSCM@PLGA-TK-PEG-SS31 is a promising treatment for osteoporosis.

Osteoarthritis (OA) is a common chronic musculoskeletal disease with heterogeneous clinical manifestations and variable responses to different treatments. Unfortunately, there is no effective disease modifying therapy at present that can alter the natural course of the disease. Cell therapy based on mesenchymal stromal cells (MSCs) may offer an attractive therapeutic option for OA with their multiple modes of action, particularly immune-regulatory and regenerative capacities.

In this narrative review, updates on mode of action based on patient's data, factors that can influence the efficacy of MSC treatment, current status in clinical application of MSCs as seen from randomized, controlled OA trials are introduced as well as the author's perspectives in the future of MSCs as OA therapeutics.

Symptomatic relief is not sufficient to justify the high cost associated with culture-expanded stem cells. Its advantages and efficacy over simple and low risk/cost modalities should be seriously reevaluated. Also, as the short-term strategy, efforts should be made to lower the cost of MSC therapy. In the future, multiomics technology may help to predict that subgroup of patients who will favorably respond to stem cell treatment, which would enhance the cost effectiveness and therapeutic benefit of MSC therapy.

The liver plays a crucial role in regulating lipid metabolism. Our study examined the impact of Exosomes derived from adipose mesenchymal stem cells (ADSCs-Exo) on lipid metabolism following liver ischemia-reperfusion injury (IRI) combined with partial hepatectomy. We developed a miniature swine model for a minimally invasive hemi-hepatectomy combined with liver IRI. In this study, we administered PBS, ADSCs-Exo, and adipose-derived stem cells (ADSCs) individually through the portal vein. Before and after surgery, we evaluated various factors including hepatocyte ultrastructure, lipid accumulation in liver tissue, and expression levels of genes and proteins associated with lipid metabolism. In addition, we measured serum and liver tissue levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (CHOL). TEM and oil red O stain indicated a significant reduction in liver steatosis following ADSCs-Exo treatment, which also elevated serum levels of HDL, LDL, TG, and CHOL. Additionally, ADSCs-Exo have been shown to significantly decrease serum concentrations of HDL, LDL, TG, and CHOL in the liver (p < 0.05). Finally, ADSCs-Exo significantly downregulated lipid synthesis-related genes and proteins, including SREBP-1, SREBP-2, ACC1, and FASN (p < 0.05), while upregulating lipid catabolism-related genes and proteins, such as PPAR-α and ACOX1 (p < 0.05). ADSCs-Exo as a cell-free therapy highlights its therapeutic potential in hepatic lipid metabolism abnormalities.

Promising therapeutic strategies are being explored to replace or regenerate the neuronal populations that are lost in patients with neurodegenerative disorders. Several research groups have attempted direct reprogramming of astrocytes into neurons by manipulating the expression of polypyrimidine tract-binding protein 1 (PTBP1) and claimed putative converted neurons to be functional, which led to improved disease outcomes in animal models of several neurodegenerative disorders. However, a few other studies reported data that contradict these claims, raising doubt about whether PTBP1 suppression truly reprograms astrocytes into neurons and the therapeutic potential of this approach. This review discusses recent advances in regenerative therapeutics including stem cell transplantations for central nervous system disorders, with a particular focus on Parkinson's and Alzheimer's diseases. We also provide a perspective on this controversy by considering that astrocyte heterogeneity may be the key to understanding the discrepancy in published studies, and that certain subpopulations of these glial cells may be more readily converted into neurons.

Crohn's disease perianal fistulas are often resistant to standard anti-tumor necrosis factor-α therapies. Mesenchymal stem cell-derived exosomes are extracellular vesicles with highly potent anti-inflammatory effects, and the previous phase of this study demonstrated their safety in the treatment of refractory perianal fistulas.

To evaluate the efficacy of mesenchymal stem cell-derived exosomes for the treatment of refractory perianal fistulas.

Nonrandomized, nonblinded single-center phase II clinical trial.

Tertiary university hospital.

Twenty-three patients were enrolled, 20 of whom completed the study. Refractory perianal fistula was defined as resistance to at least 1 course of treatment with anti-tumor necrosis factor-α therapy.

After clinical assessment and MRI, the patients received general anesthesia, and 5 mL of exosome solution was injected directly into the fistula tracts. The injections were repeated 3 times at 2-month intervals, and patients were followed monthly for 6 months after the last injection. Tissue samples from the tracts were obtained before each injection and subjected to immunohistopathological assessment. MRI data were obtained before and 6 months after the last injection.

The primary outcome of this study was fistula tract closure on clinical examination and MRI. The secondary outcome was an improvement in the discharge from the tracts.

Fistula tracts were fully closed in 12 patients (60%). Four patients showed clinical improvement, with some tracts remaining open, and 4 patients were completely resistant to treatment. A total of 43 fistula tracts were treated during the trial, 30 of which (69.7%) showed complete closure. Histopathological analysis revealed substantial reductions in local inflammation and signs of enhanced tissue regeneration. Immunohistochemical analysis of CD68, CD20, and CD31 reaffirmed these results.

Mesenchymal stem cell-derived exosomes are safe and effective for treating refractory perianal fistulas in patients with Crohn's disease. See Video Abstract .

ANTECEDENTES:Las fístulas perianales de la enfermedad de Crohn a menudo son resistentes a las terapias anti-TNF-α estándares. Los exosomas derivados de células madre mesenquimales (MSC) son vesículas extracelulares que tienen efectos antiinflamatorios muy potentes, y la fase anterior de este estudio demostró su seguridad en el tratamiento de fístulas perianales refractarias.OBJETIVO:Evaluar la eficacia de los exosomas derivados de MSC para el tratamiento de fístulas perianales refractarias.DISEÑO:Ensayo clínico de fase II, no aleatorizado y no ciego, unicéntrico.LUGARES:Hospital universitario terciario.PACIENTES:Se inscribieron veintitrés pacientes, 20 de los cuales completaron el estudio. La fístula perianal refractaria se definió como la resistencia a al menos un ciclo de tratamiento con terapia anti-TNF-α.INTERVENCIONES:Después de la evaluación clínica y la resonancia magnética, los pacientes fueron sometidos a anestesia general y se inyectaron 5 ml de solución de exosoma directamente en los trayectos de la fístula. Las inyecciones se repitieron tres veces a intervalos de 2 meses y los pacientes fueron seguidos mensualmente durante 6 meses después de la última inyección. Se obtuvieron muestras de tejido de los tractos antes de cada inyección y se sometieron a evaluación inmunohistopatológica. Los datos de imágenes de resonancia magnética se obtuvieron antes y seis meses después de la última inyección.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario de este estudio fue el cierre del trayecto de la fístula en el examen clínico y la imagen de resonancia magnética. El resultado secundario fue una mejora en la descarga de los tractos.RESULTADOS:Los trayectos de la fístula se cerraron completamente en 12 (60%) de los pacientes. Cuatro pacientes mostraron mejoría clínica, algunos tractos permanecieron abiertos y cuatro pacientes fueron completamente resistentes al tratamiento. Durante el ensayo se trataron un total de 43 trayectos fistulosos, 30 (69,7%) de los cuales mostraron un cierre completo. El análisis histopatológico reveló reducciones sustanciales en la inflamación local y signos de una mayor regeneración tisular. El análisis inmunohistoquímico del grupo de diferenciación 68, 20 y 31 reafirmó estos resultados.CONCLUSIONES:Los exosomas derivados de MSC son seguros y eficaces para el tratamiento de fístulas perianales refractarias en pacientes con enfermedad de Crohn. (Traducción-Dr. Aurian Garcia Gonzalez ).

Advances in ultrasound and prenatal diagnosis are leading an expansion in the options for parents whose fetus is identified with a congenital disease. Obstetric diseases such as pre-eclampsia and fetal growth restriction may also be amenable to intervention to improve maternal and neonatal outcomes. Advanced Medicinal Therapeutic Products such as stem cell, gene, enzyme and protein therapies are most commonly being investigated as the trajectory of treatment for severe genetic diseases moves toward earlier intervention. Theoretical benefits include prevention of in utero damage, smaller treatment doses compared to postnatal intervention, use of fetal circulatory shunts and induction of immune tolerance. New systematic terminology can capture adverse maternal and fetal adverse events to improve safe trial conduct. First-in-human clinical trials are now beginning to generate results with a focus on safety first and efficacy second. If successful, these trials will transform the care of fetuses with severe early-onset congenital disease.

Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and postoperative outcomes.

In a transplantation model, donor pigs were stratified to either the treated or the nontreated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion (EVLP) before transplantation. Treatment consisted of 3 doses of 2 × 106 cells/kg: one during EVLP and 2 after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD).

Repeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO2/FiO2 ratios and reduced incidence of PGD.

Repeated injection of lung-specific cell treatment during EVLP and post transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of postoperative outcomes.

The aim of this study was to assess the safety and efficacy of human umbilical cord mesenchymal stromal cells (hUC-MSCs) patch used as an adjuvant therapy in fetal myelomeningocele (MMC) surgery in the ovine model.

hUC-MSCs were isolated from human umbilical cords (UC) using the explant method, cultured and characterized. hUC-MSCs were then embedded in a fibrin patch. MMC were surgically created at 75 days of gestation and repaired at 89 days of gestation in sheep fetuses. Two groups were compared: the hUC-MSCs group in which MMC was repaired using a cellular patch and the control group, in which MMC was repaired using an acellular patch. Safety was evaluated by clinical ewes' monitoring during gestation, and clinical and histological examinations of lambs after birth. Efficacy was assessed by clinical neurological evaluation at 2 and 24 h of life using the sheep locomotor rating scale and by histological analyses.

Among the 17 operated lambs, nine were born alive: six in the hUC-MSCs group and three in the control group. Overall fetal loss was 47% (8/17) without differences between the two groups. No fever was reported in ewes. No tumors were detected in clinical and histological examinations in the lambs. At 24 h of life, mean Sheep Locomotor Rating score was higher in the hUC-MSCs group than in the control group: 15.0 versus 2.0 (p = 0.07). Histological analyses showed a higher large neurons density in the hUC-MSCs group in comparison with the control group: 9.9 versus 6.3/mm2 of gray matter (p = 0.04). Lambs in the hUC-MSCs group had lower fibrosis around the spinal cord and at the level of the MMC scar: 70.9 versus 253.7 μm (p = 0.10) and 691.3 versus 1684.4 μm (p = 0,18), respectively.

Ovine fetal repair of MMC using human UC-MSCs seems to be an effective and safe procedure.

Spinocerebellar ataxia (SCA) is a heterogeneous disorder characterized by impaired balance and coordination caused by cerebellar dysfunction. The absence of treatments approved by the U.S. Food and Drug Administration for SCA has driven the investigation of alternative therapeutic strategies, including stem cell therapy. Mesenchymal stem cells (MSCs), known for their multipotent capabilities, have demonstrated significant potential in treating SCA. This review examines how MSCs may promote neuronal growth, enhance synaptic connectivity, and modulate brain inflammation. Recent findings from preclinical and clinical studies are also reviewed, emphasizing the promise of MSC therapy in addressing the unmet needs of SCA patients. Furthermore, ongoing clinical trials and future directions are proposed to address the limitations of the current approaches.

A limited number of tissues can spontaneously regenerate following injury, and even fewer can regenerate to a state comparable to mature, healthy adult tissue. Mesenchymal stem cells (MSCs) were first described in the 1960s-1970s by Friedenstein et al as a small population of bone marrow cells with osteogenic potential and abilities to differentiate into chondrocytes. In 1991, Arnold Caplan coined the term "mesenchymal cells" after identifying these cells as a theoretical precursor to bone, cartilage, tendon, ligament, marrow stroma, adipocyte, dermis, muscle, and connective tissues. MSCs are derived from periosteum, fat, and muscle. Another attractive property of MSCs is their immunoregulatory and regenerative properties, which result from crosstalk with their microenvironment and components of the innate immune system. Collectively, these properties make MSCs potentially attractive for various therapeutic purposes. MSCs offer potential in sports medicine, aiding in muscle recovery, meniscal tears, and tendon and ligament injuries. In joint disease, MSCs have the potential for chondrogenesis and reversing the effects of osteoarthritis. MSCs have also demonstrated potential application to the treatment of degenerative disc disease of the cervical, thoracic, and lumbar spine.

There is limited data on third-party umbilical cord blood (UCB) or mesenchymal stem cell (MSC) transplantation-assisted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in pediatric patients.

To evaluate the efficacy and safety of UCB and MSC transplantation-assisted haplo-HSCT in pediatric patients with acute leukemia (AL).

Observational study.

Clinical data of 152 children with AL undergoing haplo-HSCT at the Children's Hospital of Soochow University between January 2020 and June 2022 were collected. The patients were divided into the haplo-HSCT + UCB group (n = 76), haplo-HSCT + MSC group (n = 31), and haplo-HSCT group (n = 45). Hematopoietic reconstruction time, complications within 30 days after transplantation, and survival and recurrence at 3 years after transplantation were compared among the groups.

Multivariate analysis revealed that haplo-HSCT with MSC and human leukocyte antigen (HLA) matching ⩾6/10 were independent factors reducing engraftment syndrome (ES) incidence. There were no significant differences among the groups in the hematopoietic reconstruction time or incidence of complications within 30 days after transplantation (p > 0.05). Overall survival, relapse-free survival, cumulative incidence of relapse, cumulative incidence of hematological relapse, and 3-year transplant-related mortality were not significantly different (p > 0.05). The incidence of adverse reactions in the haplo-HSCT + UCB group was 97.3% within 4 h after UCB infusion, with a particularly high occurrence rate of 94.7% for hypertension. No transfusion-related adverse reactions occurred after the transfusion of umbilical cord MSC in the haplo-HSCT + MSC group.

MSC-assisted haplo-HSCT can reduce ES incidence after transplantation in pediatric patients with AL. UCB infusion is associated with a high incidence of reversible hypertension. However, no adverse reactions were observed in umbilical cord MSC transfusion.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, leading to significant disability through neurodegeneration. Despite advances in the understanding of MS pathophysiology, effective treatments remain limited. Mesenchymal stem cells (MSCs) have gained attention as a potential therapeutic option due to their immunomodulatory and regenerative properties. This review examines MS pathogenesis, emphasizing the role of immune cells, particularly T cells, in disease progression, and explores MSCs' therapeutic potential. Although preclinical studies in animal models show MSC efficacy, challenges such as donor variability, culture conditions, migratory capacity, and immunological compatibility hinder widespread clinical adoption. Strategies like genetic modification, optimized delivery methods, and advanced manufacturing are critical to overcoming these obstacles. Further research is needed to validate MSCs' clinical application in MS therapy.

Cellular therapies utilizing regulatory T cells (Tregs) have flourished in the autoimmunity space as a new pillar of medicine. These cells have shown a great promise in the treatment of such devastating conditions as type 1 diabetes mellitus (T1DM), systemic lupus erythematosus (SLE) and graft versus host disease (GVHD). Novel treatment protocols, which utilize Tregs-mediated suppressive mechanisms, are based on the two main strategies: administration of immunomodulatory factors affecting Tregs or adoptive cell transfer (ACT). ACT involves extraction, in vitro expansion and subsequent administration of Tregs that could be either of autologous or allogeneic origin. Rheumatoid arthritis (RA) is another autoimmune candidate where this treatment approach is being considered. RA remains an especially challenging adversary since it is one of the most frequent and debilitating conditions among all autoaggressive disorders. Noteworthy, Tregs circulating in RA patients' blood have been proven defective and unable to suppress inflammation and joint destruction. With this knowledge, adoptive transfer of compromised autologous Tregs in the fledgling clinical trials involving RA patients should be reconsidered. In this article we hypothesize that incorporation of healthy donor allogeneic Tregs may provide more lucid and beneficial results.

To assess the safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation (MAG200) in the treatment of knee osteoarthritis over 12 months.

A single-centre, double-blind, ascending dose, randomised controlled trial. 40 participants with moderate knee osteoarthritis were randomised to receive a single intra-articular injection of MAG200 (dose cohorts:10, 20, 50, 100 ​× ​106 ​cells) or placebo. Primary objectives were safety and efficacy according to a compound responder analysis of minimal clinically important difference in pain (numerical pain rating scale [NPRS]) and function (Knee Injury and Osteoarthritis Outcome Score - Function in Daily Living subscale [KOOSADL]) at month 12. Secondary efficacy outcomes included changes from baseline in patient reported outcome measures and evaluation of disease-modification using quantitative MRI.

Treatment was well tolerated with no treatment-related serious adverse events. MAG200 cohorts reported a greater proportion of responders than placebo and demonstrated clinical and statistically significant improvement in pain and clinically relevant improvement in all KOOS subscales. MAG200 demonstrated a reproducible treatment effect over placebo, which was clinically relevant for pain in the 10 ​× ​106 dose cohort (mean difference NPRS:-2.25[95%CI:-4.47,-0.03, p ​= ​0.0468]) and for function in the 20 ​× ​106 and 100 ​× ​106 dose cohorts (mean difference KOOSADL:10.12[95%CI:-1.51,21.76, p ​= ​0.0863] and 10.81[95%CI:-1.42,23.04, p ​= ​0.0810] respectively). A trend in disease-modification was observed with improvement in total knee cartilage volume in MAG200 10, 20, and 100 ​× ​106 dose cohorts, with progression of osteoarthritis in placebo, though this was not statistically significant. No clear dose response was observed.

This early-phase study provides supportive safety and efficacy evidence to progress MAG200 to later-stage trial development.

ACTRN12617001095358/ACTRN12621000622808.

Mesenchymal Stem Cells (MSCs) are of interest in the clinic because of their immunomodulation capabilities, capacity to act upstream of inflammation, and ability to sense metabolic environments. In standard physiologic conditions, they play a role in maintaining the homeostasis of tissues and organs; however, there is evidence that they can contribute to some autoimmune diseases. Gaining a deeper understanding of the factors that transition MSCs from their physiological function to a pathological role in their native environment, and elucidating mechanisms that reduce their therapeutic relevance in regenerative medicine, is essential. We conducted a Systematic Review and Meta-Analysis of human MSCs in preclinical studies of autoimmune disease, evaluating 60 studies that included 845 patient samples and 571 control samples. MSCs from any tissue source were included, and the study was limited to four autoimmune diseases: multiple sclerosis, rheumatoid arthritis, systemic sclerosis, and lupus. We developed a novel Risk of Bias tool to determine study quality for in vitro studies. Using the International Society for Cell & Gene Therapy's criteria to define an MSC, most studies reported no difference in morphology, adhesion, cell surface markers, or differentiation into bone, fat, or cartilage when comparing control and autoimmune MSCs. However, there were reported differences in proliferation. Additionally, 308 biomolecules were differentially expressed, and the abilities to migrate, invade, and form capillaries were decreased. The findings from this study could help to explain the pathogenic mechanisms of autoimmune disease and potentially lead to improved MSC-based therapeutic applications.

Hypoxic ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and lifelong disability across the world. While therapeutic hypothermia (HT) is beneficial, it is only partially protective and adjuvant treatments that further improve outcomes are urgently needed. In high-income countries where HT is standard care, novel treatments are tested in conjunction with HT. Mesenchymal stromal cells (MSC) represent a paradigm shift in brain protection, uniquely adapting to the host cellular microenvironment. MSC have low immunogenicity and potent paracrine effects stimulating the host tissue repair and regeneration and reducing inflammation and apoptosis. Preclinical studies in perinatal brain injury suggest that MSC are beneficial after hypoxia-ischemia (HI) and most preclinical studies of MSC with HT show protection. Preclinical and early phase clinical trials have shown that allogenic administration of MSC to neonates with perinatal stroke and HIE is safe and feasible but further safety and efficacy studies of HT with MSC in these populations are needed. Combination therapies that target all stages of the evolution of injury after HI (eg HT, melatonin and MSC) show promise for improving outcomes in HIE.

Peritoneal dialysis is an important part of end-stage kidney disease replacement therapy. However, prolonged peritoneal dialysis can result in peritoneal fibrosis and ultrafiltration failure, forcing patients to withdraw from peritoneal dialysis treatment. Therefore, there is an urgent need for some effective measures to alleviate the occurrence and progression of peritoneal fibrosis. Mesenchymal stem cells play a crucial role in immunomodulation and antifibrosis. Numerous studies have investigated the fact that mesenchymal stem cells can ameliorate peritoneal fibrosis mainly through the paracrine pathway. It has been discovered that mesenchymal stem cells participate in the improvement of peritoneal fibrosis involving the following signaling pathways: TGF-β/Smad signaling pathway, AKT/FOXO signaling pathway, Wnt/β-catenin signaling pathway, TLR/NF-κB signaling pathway. Additionally, in vitro experiments, mesenchymal stem cells have been shown to decrease mesothelial cell death and promote proliferation. In animal models, mesenchymal stem cells can enhance peritoneal function by reducing inflammation, neovascularization, and peritoneal thickness. Mesenchymal stem cell therapy has been demonstrated in clinical trials to improve peritoneal function and reduce peritoneal fibrosis, thus improving the life quality of peritoneal dialysis patients.

Despite the effectiveness of insulin injections in managing hyperglycemia in type 1 diabetes mellitus (T1DM), they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential and prospects of emerging treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, pancreatic islet cell transplantation, and teplizumab. We review emerging treatment modalities for T1DM, highlighting several promising strategies with varied mechanisms and outcomes. Mesenchymal stem cells demonstrate potential in modulating the immune response and preserving or restoring beta-cell function, although variability in sources and administration routes necessitates further standardization. Similarly, MSC-derived exosomes show promise in promoting beta-cell regeneration and immune regulation, supported by early-stage studies showing improved glucose homeostasis in animal models, albeit with limited clinical data. Gene therapy, utilizing techniques like CRISPR-Cas9, offers targeted correction of genetic defects and immune modulation; however, challenges in precise delivery and ensuring long-term safety persist. Islet allotransplantation and pancreatic islet cell transplantation have achieved some success in restoring insulin independence, yet challenges such as donor scarcity and immunosuppression-related complications remain significant. Teplizumab, an anti-CD3 monoclonal antibody, has demonstrated potential in delaying T1DM onset by modulating immune responses and preserving beta-cell function, with clinical trials indicating prolonged insulin production capability. Despite significant progress, standardization, long-term efficacy, and safety continue to pose challenges across these modalities. Conclusion: While these therapies demonstrate significant potential, challenges persist. Future research should prioritize optimizing these treatments and validating them through extensive clinical trials to enhance T1DM management and improve patient outcomes.