USP13 Overexpression in BMSCs Enhances Anti-Apoptotic Ability and Guards Against Methylprednisolone-Induced Osteonecrosis in Rats.

Methylprednisolone (MPS) use is linked to increased cases of osteonecrosis of the femoral head (ONFH). Bone marrow mesenchymal stem cells (BMSCs) have shown potential for treating MPS-induced ONFH, but their effectiveness is limited by high apoptosis rates post-transplantation. We developed a pre-treatment strategy for BMSCs to improve their viability. In a rat model of MPS-induced ONFH, we evaluated the effects of USP13 overexpression in BMSCs through micro-CT, HE staining, and TUNEL staining. USP13-overexpressing BMSCs significantly reduced ONFH severity compared to plain BMSCs and direct lentivirus injection. USP13 also protected BMSCs from MPS-induced apoptosis by modulating PTEN and reducing AKT phosphorylation. This led to decreased expression of apoptotic genes and proteins in USP13-overexpressing BMSCs. Our findings highlight USP13 as a promising target for enhancing BMSC survival and efficacy in treating MPS-induced ONFH.

Using carbohydrate-based polymers to facilitate testicular regeneration.

Male infertility is a significant global issue affecting 60-80 million people, with 40%-50% of cases linked to male issues. Exposure to radiation, drugs, sickness, the environment, and oxidative stress may result in testicular degeneration. Carbohydrate-based polymers (CBPs) restore testis differentiation and downregulate apoptosis genes. CBP has biodegradability, low cost, and wide availability, but is at risk of contamination and variations. CBP shows promise in wound healing, but more research is required before implementation in healthcare. Herein, we discuss the recent advances in engineering applications of CBP employed as scaffolds, drug delivery systems, immunomodulation, and stem cell therapy for testicular regeneration. Moreover, we emphasize the promising challenges warranted for future perspectives.

Injectable amnion hydrogel-mediated delivery of adipose-derived stem cells for osteoarthritis treatment.

Current treatment strategies for osteoarthritis (OA) predominantly address symptoms with limited disease-modifying potential. There is a growing interest in the use of adipose-derived stem cells (ADSCs) for OA treatment and developing biomimetic injectable hydrogels as cell delivery systems. Biomimetic injectable hydrogels can simulate the native tissue microenvironment by providing appropriate biological and chemical cues for tissue regeneration. A biomimetic injectable hydrogel using amnion membrane (AM) was developed which can self-assemble in situ and retain the stem cells at the target site. In the present study, we evaluated the efficacy of intraarticular injections of AM hydrogels with and without ADSCs in reducing inflammation and cartilage degeneration in a collagenase-induced OA rat model. A week after the induction of OA, rats were treated with control (phosphate-buffered saline), ADSCs, AM gel, and AM-ADSCs. Inflammation and cartilage regeneration was evaluated by joint swelling, analysis of serum by cytokine profiling and Raman spectroscopy, gross appearance, and histology. Both AM and ADSC possess antiinflammatory and chondroprotective properties to target the sites of inflammation in an osteoarthritic joint, thereby reducing the inflammation-mediated damage to the articular cartilage. The present study demonstrated the potential of AM hydrogel to foster cartilage tissue regeneration, a comparable regenerative effect of AM hydrogel and ADSCs, and the synergistic antiinflammatory and chondroprotective effects of AM and ADSC to regenerate cartilage tissue in a rat OA model.

Comparative evaluation of bone marrow and dental pulp mesenchymal stem cells for motor functional recovery in rat sciatic nerve injury.

This study delves into the impact of mesenchymal stem cells derived from bone marrow (BM-MSCs) and those sourced from dental pulp (DP-MSCs) on the recovery of motor function and morphological aspects of the rat's sciatic nerve after crush injuries. The findings highlight that the groups treated with BM-MSCs, DP-MSCs or a combination of both (BM + DP-MSCs) displayed enhanced sciatic functional index values when juxtaposed with the sham group. This points to bettered motor functionalities. A deeper morphological analysis showed that all the groups had retained perineurium structure and fascicular arrangement. Notably, the sham and BM-MSCs groups had very few inconsistencies. All groups showed standard vascular density. Remarkably, the combined treatment group (BM + DP-MSCs) presented diminished oedema and a lower count of inflammatory cells. Through immunohistochemical methods, the presence of S100 expression was noted in the groups that underwent treatment. In summation, the study suggests that both BM-MSCs and DP-MSCs, whether used singly or in combination, can significantly aid in motor function restoration and morphological enhancements. An interesting observation from our research and earlier studies is that stem cells from dental pulp, which are sourced with less discomfort from milk and wisdom teeth, show a heightened propensity to evolve into nerve cells. This is in contrast to the more uncomfortably acquired BM-MSCs.

Metabolically Glycoengineered Neural Stem Cells Boost Neural Repair After Cardiac Arrest.

Cardiac arrest (CA)-induced cerebral ischemia remains challenging with high mortality and disability. Neural stem cell (NSC) engrafting is an emerging therapeutic strategy with considerable promise that, unfortunately, is severely compromised by limited cell functionality after in vivo transplantation. This groundbreaking report demonstrates that metabolic glycoengineering (MGE) using the "Ac5ManNTProp (TProp)" monosaccharide analog stimulates the Wnt/ß-catenin pathway, improves cell adhesion, and enhances neuronal differentiation in human NSCs in vitro thereby substantially increasing the therapeutic potential of these cells. For the first time, MGE significantly enhances NSC efficacy for treating ischemic brain injury after asphyxia CA in rats. In particular, neurological deficit scores and neurobehavioral tests experience greater improvements when the therapeutic cells are pretreated with TProp than with "stand-alone" NSC therapy. Notably, the TProp-NSC group exhibits significantly stronger neuroprotective functions including enhanced differentiation, synaptic plasticity, and reduced microglia recruitment; furthermore, Wnt pathway agonists and inhibitors demonstrate a pivotal role for Wnt signaling in the process. These findings help establish MGE as a promising avenue for addressing current limitations associated with NSC transplantation via beneficially influencing neural regeneration and synaptic plasticity, thereby offering enhanced therapeutic options to boost brain recovery following global ischemia.

Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale.

BACKGROUND: Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. METHODS: Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. RESULTS: In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. CONCLUSIONS: UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Multifunctional Biodegradable Conductive Hydrogel Regulating Microenvironment for Stem Cell Therapy Enhances the Nerve Tissue Repair.

The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstrates that the rationally designed biodegradable multifunctional hydrogel significantly enhances nerve tissues repair.

Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell-Mediated Biomedical Applications.

Stem cell-related therapeutic technologies have garnered significant attention of the research community for their multi-faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell-cell and cell-matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell-related research. Microfluidics offers an intriguing platform to produce stem cell-laden hydrogel microparticles (SCHMs) owing to its ability to manipulate the fluids at the micrometer scale as well as precisely control the structure and composition of microparticles. In this review, the typical biomaterials and crosslinking methods for microfluidic encapsulation of stem cells as well as the progress in droplet-based microfluidics for the fabrication of SCHMs are outlined. Moreover, the important biomedical applications of SCHMs are highlighted, including regenerative medicine, tissue engineering, scale-up production of stem cells, and microenvironmental simulation for fundamental cell studies. Overall, microfluidics holds tremendous potential for enabling the production of diverse hydrogel microparticles and is worthy for various stem cell-related biomedical applications.

Current guidelines, challenges and future recommendations for regulation of stem cell research and therapy: a commentary.

In recent years, Malaysia has seen a surge in stem cell therapy for various medical conditions. However, the regulation of stem cell research and therapy in Malaysia faces several challenges such as the emergence of unregulated clinics and a lack of specific legislation. Some urgent measures, including enactment of specific laws, strengthened monitoring, as well as increased public awareness and education, are crucial. Therefore, stem cell therapy regulation requires concerted efforts by the policymakers, regulator bodies and healthcare professionals. This commentary discusses the current guidelines and challenges in Malaysian stem cell therapy regulation and proposes some future recommendations that could pave the way for responsible progress of stem cell research and therapy globally.

Scalable manufacture of therapeutic mesenchymal stromal cell products on customizable microcarriers in vertical wheel bioreactors that improve direct visualization, product harvest, and cost.

BACKGROUND AIMS: Human mesenchymal stromal cells (hMSCs) and their secreted products show great promise for treatment of musculoskeletal injury and inflammatory or immune diseases. However, the path to clinical utilization is hampered by donor-tissue variation and the inability to manufacture clinically relevant yields of cells or their products in a cost-effective manner. Previously we described a method to produce chemically and mechanically customizable gelatin methacryloyl (GelMA) microcarriers for culture of hMSCs. Herein, we demonstrate scalable GelMA microcarrier-mediated expansion of induced pluripotent stem cell (iPSC)-derived hMSCs (ihMSCs) in 500 mL and 3L vertical wheel bioreactors, offering several advantages over conventional microcarrier and monolayer-based expansion strategies. METHODS: Human mesenchymal stromal cells derived from induced pluripotent cells were cultured on custom-made spherical gelatin methacryloyl microcarriers in single-use vertical wheel bioreactors (PBS Biotech). Cell-laden microcarriers were visualized using confocal microscopy and elastic light scattering methodologies. Cells were assayed for viability and differentiation potential in vitro by standard methods. Osteogenic cell matrix derived from cells was tested in vitro for osteogenic healing using a rodent calvarial defect assay. Immune modulation was assayed with an in vivo peritonitis model using Zymozan A. RESULTS: The optical properties of GelMA microcarriers permit noninvasive visualization of cells with elastic light scattering modalities, and harvest of product is streamlined by microcarrier digestion. At volumes above 500 mL, the process is significantly more cost-effective than monolayer culture. Osteogenic cell matrix derived from ihMSCs expanded on GelMA microcarriers exhibited enhanced in vivo bone regenerative capacity when compared to bone morphogenic protein 2, and the ihMSCs exhibited superior immunosuppressive properties in vivo when compared to monolayer-generated ihMSCs. CONCLUSIONS: These results indicate that the cell expansion strategy described here represents a superior approach for efficient generation, monitoring and harvest of therapeutic MSCs and their products.

Medical Management for Fracture Prevention in Children with Osteogenesis Imperfecta.

There are no licensed treatments for children with osteogenesis imperfecta. Children currently receive off-label treatment with bisphosphonates, without any consistent approach to dose, drug or route of administration. Meta-analyses suggest that anti-fracture efficacy of such interventions is equivocal. New therapies are undergoing clinical trials, and it is likely that one or more will receive marketing authorisation within the next three to five years. The long-term outcome from such interventions will need to be studied carefully well beyond the period over which the clinical trials are conducted, and a consistent approach to the collection of data in this regard will be needed as a major collaborative effort.

Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by increased bone fragility largely caused by defects in structure, synthesis, or post-translational processing of type I collagen. Drugs currently used to improve skeletal health in OI were initially developed to treat osteoporosis and clinical trials are ongoing to study their effectiveness in OI adults. Additionally, novel bone-protective agents are in preclinical studies and various phases of OI clinical trials. This review summarizes current knowledge on available pharmacologic agents and current drug trials involving OI participants. A PubMed online database search of all study types published in the English language using the terms "osteogenesis imperfecta," "OI," and "brittle bone disease" was performed in August 2022. Articles screened were restricted to adults. A ClinicalTrials.gov database search of all studies involving "osteogenesis imperfecta" was performed in August 2023. Although clinical trial data are limited, bisphosphonates and teriparatide may be useful in improving bone mineral density. As of yet, no clinical trials are available that adequately evaluate the usefulness of current therapies in reducing fracture risk. Several therapeutics, including teriparatide, setrusumab, anti-TGF-ß antibodies, and allogeneic stem cells, are being studied in clinical trials. Preclinical studies involving Dickkopf-1 antagonists present promising data in non-OI bone disease, and could be useful in OI. Research is ongoing to improve therapeutic options for adults with OI and clinical trials involving gene-editing may be possible in the coming decade.

Unravelling the Parkinson's puzzle, from medications and surgery to stem cells and genes: a comprehensive review of current and future management strategies.

Parkinson's disease (PD) is a neurodegenerative disorder, prevalent in the elderly population. Neuropathological hallmarks of PD include loss of dopaminergic cells in the nigro-striatal pathway and deposition of alpha-synuclein protein in the neurons and synaptic terminals, which lead to a complex presentation of motor and non-motor symptoms. This review focuses on various aspects of PD, from clinical diagnosis to currently accepted treatment options, such as pharmacological management through dopamine replacement and surgical techniques such as deep brain stimulation (DBS). The review discusses in detail the potential of emerging stem cell-based therapies and gene therapies to be adopted as a cure, in contrast to the present symptomatic treatment in PD. The potential sources of stem cells for autologous and allogeneic stem cell therapy have been discussed, along with the progress evaluation of pre-clinical and clinical trials. Even though recent techniques hold great potential to improve the lives of PD patients, we present the importance of addressing the safety, efficacy, ethical, cost, and regulatory concerns before scaling them to clinical use.

Mesenchymal stem cell therapy for Crohn's perianal fistula-a real-world experience.

AIM: Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment. METHODS: All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented. RESULTS: Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events. CONCLUSION: In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.

Status of research on the development and regeneration of hair follicles.

Hair loss, or alopecia, is a prevalent condition in modern society that imposes substantial mental and psychological burden on individuals. The types of hair loss, include androgenetic alopecia, alopecia areata, and telogen effluvium; of them, androgenetic alopecia is the most common condition. Traditional treatment modalities mainly involve medical options, such as minoxidil, finasteride and surgical interventions, such as hair transplantation. However, these treatments still have many limitations. Therefore, exploring the pathogenesis of hair loss, specifically focusing on the development and regeneration of hair follicles (HFs), and developing new strategies for promoting hair regrowth are essential. Some emerging therapies for hair loss have gained prominence; these therapies include low-level laser therapy, micro needling, fractional radio frequency, platelet-rich plasma, and stem cell therapy. The aforementioned therapeutic strategies appear promising for hair loss management. In this review, we investigated the mechanisms underlying HF development and regeneration. For this, we studied the structure, development, cycle, and cellular function of HFs. In addition, we analyzed the symptoms, types, and causes of hair loss as well as its current conventional treatments. Our study provides an overview of the most effective regenerative medicine-based therapies for hair loss.

Comprehensive characterisation and cryopreservation optimisation of buffalo (Bubalus bubalis) adipose tissue-derived mesenchymal stem cells.

Over half of the world's buffalo (Bubalus bubalis) inhabit India, and buffaloes frequently encounter health challenges that resist conventional treatments, prompting the exploration of alternative therapeutic strategies. One promising approach is stem cell therapy, particularly multipotent mesenchymal/stromal stem cells (MSCs). These cells have shown significant efficacy in addressing various diseases in livestock that exhibit resistance to conventional therapies. Adipose tissue-derived MSCs (ADSCs) have garnered attention due to their accessibility and robust expansion potential. The current study comprehensively characterises buffalo ADSCs (bADSCs), confirming their identity as MSCs capable of differentiating into diverse cell lineages-the identified characteristics position bADSCs as promising candidates for applications in regenerative medicine, applicable in veterinary contexts. Notably, the study established that a cryoprotective solution comprising 10 % dimethyl sulfoxide and 90 % fetal bovine serum is optimal for preserving bADSCs. This cryoprotective solution maintains vital parameters, including viability, apoptosis, senescence, cell adherence, adherent cell viability, metabolic and clonogenic efficiency, and the activity of reactive oxygen species and trilineage differentiation potential following thawing. These findings lay the foundation for developing a cryo-banking system for bADSCs. Subsequent research efforts are focused on exploring the therapeutic potential of bADSCs in specific disease models and clinical settings. The outcomes of such investigations may pave the way for innovative and effective treatments, further enhancing our understanding of the regenerative capabilities of bADSCs.

Evaluating the impact of mesenchymal stem cell therapy on visual acuity and retinal nerve fiber layer thickness in optic neuropathy patients: a comprehensive systematic review and meta-analysis.

BACKGROUND: Stem cell therapy has emerged as a potential therapeutic avenue for optic neuropathy patients. To assess its safety and efficacy, we conducted a systematic review and meta-analysis, focusing on the latest evidence pertaining to the improvement of visual acuity (VA) through stem cell therapy. METHODS: We analyzed Each database from its inception until June 2024. PubMed, Scopus, and Google Scholar were systematically searched to identify the included studies. Data were extracted regarding the year of publication, the name of the first author, sample size, VA (Log Mar), and Retinal Nerve Fiber Layer (RNFL) thickness. PRISMA protocol was used as a guide to perform this meta-analysis. STATA 16 was used for statistical analysis. RESULTS: A total of 66 eyes were examined in seven papers. Based on the meta-analysis, the mean VA (Log MAR) of patients with optic neuropathy improved from 0.90 to 0.65 following stem cell therapy intervention (p-value = 0.001). The thickness of the RNFLs did not demonstrate a significant change (p-value was 0.174). CONCLUSION: According to this systematic review and meta-analysis, stem cell therapy may improve the visual acuity of patients with optic neuropathy. Aside from the traditional therapy that can be provided to patients with optic neuropathy, stem cell therapy may also be beneficial.

Mini review: human clinical studies of stem cell therapy in keratoconus.

Treatment of keratoconus is one of the most interesting research fields for researchers in the world. Regenerative medicine based on human stem cells in the treatment of keratoconus has recently received attention. Despite extensive laboratory and animal studies in regenerative medicine of cornea, there are limited clinical studies in keratoconus. These studies showed promising results of stem cell therapy. In initial studies, the transplantation of these cells into stroma was associated with increased vision and improved corneal parameters without side effects. In this article, we tried to review different aspects of keratoconus stem cell therapy, including cell extraction and culture, surgical procedure, effectiveness and safety of this method in human clinical studies.

A comprehensive meta-analysis of stem cell therapy for liver failure: Assessing treatment efficacy and modality.

INTRODUCTION AND OBJECTIVES: This meta-analysis aims to evaluate the efficacy of stem cell therapy (SCT) for liver failure. MATERIALS AND METHODS: The study adhered to the recommended guidelines of the PRISMA statement. Eligible studies published prior to May 13, 2023, were comprehensively searched in databases including PubMed, Web of Science, and Embase. Quality assessment was conducted using the Cochrane risk-of-bias tool, and the standard mean differences were calculated for the clinical parameters. The hazard ratios were determined by extracting individual patient data from the Kaplan-Meier curve. RESULTS: A total of 2,937 articles were retrieved, and eight studies were included in the final analysis. Most of the studies focused on HBV-related liver failure and were randomized controlled trials. All studies utilized mesenchymal stem cells (MSCs), with the majority (62.5%) being allogeneic. The analysis revealed that combining stem cell therapy with standard medical treatment or plasma exchange significantly enhanced patient survival and reduced MELD scores. Specifically, allogeneic stem cells showed superior efficacy in improving survival outcomes compared to autologous stem cells. Furthermore, deep vessel injection plus a single injection demonstrated better effectiveness than peripheral vessel injection plus multiple injections in reducing MELD scores. CONCLUSIONS: This comprehensive analysis underscores the potential of MSC therapy in significantly improving survival and clinical outcomes in patients with liver failure, highlighting the superior benefits of allogeneic MSCs and deep vessel plus single injection administration.

Interrogating erectile dysfunction and evaluating novel therapeutic frontiers, with emphasis on stem cell strategies.

Male infertility arises from a complex interplay of factors affecting reproductive organs and various physiological pathways. Among these, erectile dysfunction (ED), a widespread global issue, plays a key role. While existing ED treatments address some aspects, achieving complete reversibility and avoiding side effects remains a challenge. In this context, stem cell therapy emerges as a promising, potentially transformative approach. Preliminary evidence from preclinical animal models and clinical trials highlights stem cell therapy's remarkable efficacy and effectiveness for ED. This novel strategy offers several advantages, including enhanced effectiveness and a reported absence of adverse side effects. This review delves into the causes of male infertility, with a particular focus on ED and its pathophysiology. We explore the current treatment landscape, highlighting therapy's existing strategies' limitations and stem cell therapy's unique potential. By examining relevant preclinical and clinical studies, we provide a comprehensive picture of this innovative approach and its promising future in restoring men's fertility and quality of life.