Focal post-traumatic cartilage lesions frequently progress to early osteoarthritis, highlighting the limited regenerative capacity of adult articular cartilage. Compared to native tissue, conventional surgical interventions often produce fibrocartilage with inferior biomechanical properties, representing a persistent therapeutic challenge. This review assessed preclinical studies exploring cartilage repair strategies using autologous mesenchymal stem cells (MSCs) in animal models. MSCs therapies demonstrated superior cartilage regeneration, matrix organization, and integration into the surrounding tissue compared to the control groups. The most efficient source was found to be bone marrow - derived mesenchymal stem cells (BM-MSCs) combined with biodegradable scaffolds, suggesting their potential in tissue engineering applications. Despite methodological heterogeneity across studies - including variations in stem cells sources, implant types, and deliver strategies - cumulative evidence strongly supports the regenerative potential of autologous MSCs for cartilage repair. Current research identifies key knowledge gaps, including the absence of standardized experimental protocols and limited insight into the mechanisms of tissue remodeling and maturation. Collectively, these gaps limit direct clinical translation, highlighting the need for further, standardized studies in large animal models with long-term follow-up (>2 years) to assess integration, functional maturation, and the full regenerative potential of the repair tissue.

Wound healing is complex, and hard-to-heal (chronic) wounds pose significant treatment challenges, especially in adults. Micrografts (MGs) are emerging as a promising treatment for wounds refractory to conventional approaches. MG involves transplanting a stem cell suspension to the wound to promote healing. Scientific studies on MG are increasing; however, a systematic review is needed for a comprehensive understanding of its efficacy.

Male infertility is a rising problem globally with male factors contributing up to 50% of all couple infertility cases. The sperm quality decline raises serious concerns regarding future population sustainability and male reproductive health. Adipose-derived mesenchymal stem cell (AdMSC) secretome, defined as a cell-free product comprising paracrine factors secreted by these cells, has emerged as a promising cell-free regenerative therapy for testicular injury, offering advantages of accessibility and therapeutic potential. This systematic review aimed to evaluate the effectiveness of AdMSC secretome in chemically induced testicular injury models.

Orally derived mesenchymal stem cells (OMSCs) are an emerging source of cells for treating vascular diseases (VDs). In this systematic review and meta-analysis, for the first time, we reviewed the published preclinical studies that examined the potential of OMSCs and their secretome in treating VDs, focusing on their efficacy and therapeutic mechanism. We electronically searched PubMed, Embase, and Web of Science, from the inception of the databases to December 31, 2024, for relevant literature from peer-reviewed journals. The studies focused on treating VDs in animal models using the OMSC-based strategy were included in the review. The articles were classified by disease, injury model, and outcome. A meta-analysis of the OMSC treatment effects on the cerebral ischemia (CI) infarct volume was conducted using random-effects and fixed-effects models. Forty-one studies were included and classified by type: CI, hypoxic-ischemic encephalopathy (HIE), myocardial ischemia (MI), hindlimb ischemia (HI), and others. Each study presented varying degrees of evidence that OMSCs had positive biological and functional effects on the treatment outcomes of VDs, mainly via paracrine effects. Pooled analysis showed that the effect of OMSC treatment compared with control on infarct volume was − 2.19 (95% confidence interval: − 3.01, − 1.37, p < 0.01) with the random-effects model and − 1.87 (95% confidence interval: − 2.44, − 1.29, p < 0.01) with the fixed-effects model. These results showed that OMSCs can significantly reduce the infarct volume in animal models of CI. Overall, OMSCs show promising potential for treating VDs mainly because of their secretome. However, before moving on to clinical trials, more high-quality preclinical studies with detailed analyses of possible off-target effects are needed.

Exosomes, tiny extracellular vesicles (EVs) from different cell types, are gaining attention in dermatology due to their unique properties. They enhance cell communication, transport bioactive substances, and influence immune responses, making them valuable for skin regeneration, wound healing, and addressing skin conditions.

ObjectiveTo systematically review and quantitatively synthesize in vivo evidence on extracellular vesicle (EV)-based therapies for regenerative endodontic procedures, focusing on mineralization and angiogenesis outcomes.MethodsWe conducted a systematic review and meta-analysis of in vivo preclinical dentoalveolar/regenerative endodontic models comparing EV-based interventions (exosomes/microvesicles/apoptotic bodies), alone or with scaffolds, versus control conditions. Searches were performed in Web of Science Core Collection and Scopus from inception to 31 December 2025, with reference screening. Random-effects meta-analyses pooled standardized mean differences (SMDs) for mineralization and angiogenesis; heterogeneity was assessed using I2. Risk of bias was evaluated using the Systematic Review Centre for Laboratory animal Experimentation tool.ResultsTwenty-one studies met inclusion criteria; seven were included in the mineralization meta-analysis and five in the angiogenesis meta-analysis. EV-based therapies significantly increased mineralization versus controls (SMD = 6.43; 95% confidence interval (CI) [3.13-9.73]; I2 = 91%) and angiogenesis (SMD = 7.89; 95% CI [3.94-11.85]; I2 = 82%). Subgroup analyses suggested stronger effects for EVs derived from dental pulp stem cells, stem cells from human exfoliated deciduous teeth, and stem cells from apical papilla. Risk of bias was predominantly unclear due to limited reporting of randomization and blinding. Considerable heterogeneity, small numbers of pooled studies, and variability in EV isolation, characterization, dosing, and outcome assessment limit generalizability and translation.ConclusionsEV-based therapies enhance mineralization and angiogenesis in preclinical regenerative endodontic models, with dental stem cell-derived EVs showing the greatest apparent potential. However, effect sizes should be interpreted cautiously given very high heterogeneity and methodological/reporting limitations.PROSPERO registration: Centre for Reviews and Dissemination 420251107328.

Background: Myocardial ischemic injury, encompassing acute myocardial infarction (MI) and ischemia/reperfusion (I/R) injury, remains a major cause of cardiac morbidity and mortality worldwide, and is driven by interconnected molecular and cellular processes, including cardiomyocyte apoptosis, inflammatory activation, mitochondrial dysfunction, oxidative stress, and impaired angiogenesis. Mesenchymal stem cell (MSC)-derived exosomes have emerged as a promising cell-free nanotherapeutic strategy for cardiac repair due to their ability to transfer bioactive molecules that modulate multiple signaling networks involved in myocardial survival and regeneration. This systematic review aimed to synthesize evidence on the mechanistic basis of MSC-derived exosome mediated cardioprotection in myocardial ischemic injury. Methods: A systematic search of Ovid MEDLINE, Scopus, and Web of Science was conducted to identify studies investigating the effects of MSC-derived exosomes on myocardial ischemic injury. Eligible studies included clinical and preclinical models of MI or I/R injury assessing functional, biochemical, and molecular outcomes. Results: Seven preclinical studies published between 2015 and 2025 met the inclusion criteria. Exosome administration consistently improved cardiac function, reduced infarct size, and preserved myocardial architecture. Biochemical analyses revealed decreased cardiac injury markers, alongside suppressed apoptosis, inflammation, and oxidative stress. Mechanistically, MSC-derived exosomes delivered regulatory miRNAs (e.g., miR-19a, miR-125b, miR-205, miR-294) and lncRNAs (HAND2-AS1) that modulated key signaling pathways including PI3K/Akt, JAK2/STAT3, HAND2-AS1/miR-17-5p/Mfn2, and HIF-1α/VEGF. These molecular effects collectively inhibited apoptotic and inflammatory responses, enhanced mitochondrial integrity, and promoted angiogenesis and myocardial repair. Conclusions: MSC-derived exosomes confer robust cardioprotection against myocardial ischemic injury through integrated anti-apoptotic, anti-inflammatory, antioxidant, and pro-angiogenic mechanisms. Their multifaceted bioactivity, low immunogenicity, and potential for targeted delivery highlight their potential as a next-generation nanomedicine for ischemic heart disease. Future studies should emphasize standardized exosome production, mechanistic profiling, and translational validation in large-animal and clinical models.

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as "cartilage damage", "cartilage injuries", "amnion" and "amniotic membrane", 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant-2023 SATU Joint Research Scheme Program: ST007-2024.

Background: Mastoid obliteration following canal wall down mastoidectomy reduces cavity-related morbidity. Conventional obliteration materials act primarily as passive fillers, whereas tissue engineering (TE) strategies aim to achieve biologically active bone regeneration. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched from January 2010 to December 2025. Studies evaluating tissue engineering-assisted mastoid obliteration involving growth factors, mesenchymal stem cells, polymer scaffolds, or 3D-printed constructs were included. Results: Fifteen studies met inclusion criteria (12 preclinical and three clinical). Polymer-supported MSC constructs demonstrated the most consistent osteogenic enhancement in animal models. Clinical evidence remains limited to small PRP-based case series. Conclusions: Preliminary evidence suggests that tissue engineering-assisted mastoid obliteration has regenerative potential, although the evidence is limited by predominantly preclinical data and a moderate-to-high risk of bias. Standardized outcome measures and well-designed prospective clinical studies are required to confirm long-term safety and efficacy.

Diagnostic evaluation and management of nontraumatic osteonecrosis of the femoral head (ONFH) vary substantially. This systematic review was conducted to inform development of the Association Research Circulation Osseous (ARCO) clinical practice guideline for diagnosis and treatment of ARCO stages I to III ONFH.

Keloids and hypertrophic scars are fibroproliferative disorders with high recurrence rates, lacking a definitive treatment standard. This review systematically evaluates current therapies and their effectiveness in treating keloid and hypertrophic scars.

Diabetic foot ulcers (DFUs) represent a debilitating complication of diabetes characterized by high rates of morbidity and mortality, yet conventional management often yields limited efficacy. Although cell-based therapies offer a promising therapeutic avenue, their clinical efficacy and optimal target populations remain to be definitively established.

Vascularized composite allotransplantation (VCA) enables functional reconstruction for patients with extensive tissue defects, but has obstacles such as immune rejection, lifelong immunosuppression, and systems-level barriers that limit widespread adoption. VCA has rapidly evolved through novel surgical, immunologic, and bioengineering technologies. This systematic review synthesizes the current landscape of emerging VCA technologies, identifies literature gaps, and emphasizes opportunities for future research. We conducted a systematic literature review of PubMed and Embase with supplemental manual reference review. English-language experimental studies reporting novel VCA technologies and innovations published after 2004 were included. Case reports, reviews, studies without technological innovation, and non-English publications were excluded. Seventy-two studies fit the inclusion criteria. Novel immunomodulation strategies including belatacept, phototherapy, siRNA therapeutics, and tolerance induction via regulatory T-cells show potential to reduce systemic immunosuppression, while mesenchymal stem cell approaches may increase graft tolerance. On another front, advanced surgical techniques with real-time monitoring and nerve regeneration protocols are looking to promote functional recovery. Digital innovations like 3D modeling and virtual surgical planning allow for patient-specific preoperative planning and intra-operative assistance. In parallel, machine perfusion and cryopreservation extend tolerable ischemia times and may also enable early rejection detection. Similarly, biomarkers and imaging provide early and noninvasive rejection prediction. On a bigger scale, patient selection incorporating evidence-backed psychosocial factors and communication training work to address systems-level barriers to expand access. Ongoing research to translate these innovations into clinical practice will be important in realizing the potential of VCA.

Decellularized extracellular matrices (dECMs) have gained increasing attention in regenerative dentistry due to their ability to replicate aspects of the native cellular microenvironment while reducing immunogenicity. Dental-derived stem cells exhibit regenerative and immunomodulatory properties, making them promising candidates for tissue repair when combined with biologically derived scaffolds such as dECMs.

Knee osteoarthritis (OA) causes significant chronic pain and disability. Current non-operative treatments are largely symptom-modifying. While intra-articular mesenchymal stem cell (MSC) therapies are promising, randomized controlled trials (RCTs) report inconsistent results due to heterogeneity in cell sources, preparations, and techniques.

Traditional root canal treatment removes the infection successfully, but the vitality of pulp-dentin complex cannot be restored. The birth of regenerative endodontics is a biologically driven technique that seeks to restore pulp vitality, coax the root into forming, and maintain long-term functionality of the tooth. This review critically appraises the available evidence regarding regenerative endodontics and stem cell-based therapies in clinical practice. PRISMA guidelines were adopted for a comprehensive search of the literature in PubMed, Scopus, Web of Science, Cochrane Library, and Embase. Human trials reporting cellular transplantation-based or cell-homing regenerative approaches were considered. Five eligible human studies were included. Stem cell sources comprised dental pulp stem cells and stem cells from human exfoliated deciduous teeth, while platelet concentrates and collagen scaffolds were commonly used. Clinical outcomes included restoration of pulp vitality, apical closure, dentin wall thickening, and periapical healing, with no major adverse events reported. Stem cell-based regenerative endodontics demonstrates promising clinical potential but remains constrained by small sample sizes, protocol heterogeneity, and limited follow-up. Standardized methodologies and long-term randomized controlled trials are needed before integration into routine practice.

Given the limitations of current treatments for Alzheimer's disease (AD), this study aims to comprehensively evaluate the therapeutic efficacy of human umbilical cord mesenchymal stem cells (hUCMSCs) in AD mouse models through a systematic review and meta-analysis. Additionally, we explore the impact of transplantation dose and route on treatment outcomes to identify the optimal window for clinical application.