Regenerative medicine最新文献

Latest developments in the field of Advanced Therapy Medicinal Products and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in June 2025.

Background: Hepatocyte transplantation has gained importance as an alternative treatment to orthotopic liver transplantation for end-stage liver disease. This study explores the modification of the hepatocyte matrix implant (HMI) procedure by replacing islet cells with conditioned medium (CM) derived from human umbilical cord-MSC (hUC-MSC) supplementation to alleviate liver cirrhosis in a rat model.

Methods: The male Sprague Dawley rats were induced liver cirrhosis using thioacetamide for 11 weeks, and implanted with matrices on the small bowel mesentery, according to the groups. Four groups were assessed: blank matrix (cell-free), hepatocytes seeded-matrix (Hep), hepatocytes+islets co-seeded-matrix (Hep:Islet), and hepatocytes seeded-matrix supplemented with CM (Hep+CM).

Results: In vitro, the Hep+CM group showed significantly higher hepatocyte proliferation than the Hep:Islet group, though albumin production was similar. The in vivo study further confirmed that the implanted hepatocytes remained viable and were able to produce albumin for at least 4 months post-implantation. Liver function parameters were shown to be improved in Hep:Islet and Hep+CM groups. Notably, collagen deposition in the liver was lower in Hep:Islet and Hep+CM groups compared to other groups.

Conclusion: These findings suggest that CM can effectively replace islet in supporting hepatocyte proliferation and function, enhancing the therapeutic potential of HMI procedure. No writing assistance was utilized in the production of this manuscript or liver cirrhosis treatment.

Despite the discovery, nearly 40 years ago, that mutations in the dystrophin gene were responsible for Duchenne muscular dystrophy (DMD), a cure for this devastating disease remains elusive. Considerable effort worldwide is focused on understanding DMD and devising treatments, including gene-, cell-, and pharmacologic-based therapies. More than 400 clinical trials for DMD and/or the related Becker muscular dystrophy (BMD) have been registered with clinicaltrials.gov, with many in various stages of completion, and more than 40 having been terminated or withdrawn. The failure of interventions in clinical trials represents a significant emotional burden for the entire DMD community. While some gene-based therapies are being approved, these can be expensive, and currently tend to target specific mutations. Several cell-based therapies and tissue engineering strategies are also currently in development. Of the many pharmacotherapies to address aspects of the pathophysiology of DMD, like preserving muscle fibers, enhancing regeneration, and increasing strength, glucocorticoids remain the most efficacious for attenuating the disease progression. Successful pharmacotherapies may enable patients to take advantage of perfected gene therapies when they eventually become available. Here, we explore the therapeutic merit of different pharmacotherapies currently under consideration and provide an update on recent advances in gene therapies for DMD.

Gene therapy has ushered in a new era for the treatment of inherited retinal diseases (IRDs). The approval of voretigene neparvovec-rzyl (Luxturna) for RPE65-associated retinal dystrophy marked a pivotal milestone, establishing proof-of-concept that gene addition can restore visual function in IRDs. However, the success of Luxturna is tempered by the reality that it applies to a narrow subset of IRDs, and that no other IRD gene therapy has thus far received regulatory approval. This review outlines the current landscape of IRD gene therapy, including trials for several forms of IRD including achromatopsia, choroideremia, Leber congenital amaurosis, X-linked retinitis pigmentosa, and X-linked retinoschisis. We highlight the central challenges facing the field: narrow gene- or variant-specific indications, vector limitations, and reliance on suboptimal clinical trial endpoints. The review also discusses emerging strategies - including dual AAV and split-intein vectors, non-viral delivery platforms, and precision gene editing technologies such as CRISPR, base editing, and prime editing. These innovations promise to expand therapeutic reach. Finally, we emphasize the need for improved regulatory frameworks and ethical considerations for gene-based therapies for IRD. The field now stands at a critical juncture, where the lessons of Luxturna can inform a more scalable, inclusive, and transformative future.

Background/aims: Mesenchymal stem/stromal cells (MSCs) are widely investigated for regenerative therapies, yet current expansion methods often compromise their stem-like properties, limiting large-scale clinical translation. We aimed to evaluate whether a novel hydrogel-based Bio-Block® platform preserved intrinsic adipose-derived MSC (ASCs) phenotype and secretome compared with conventional systems.

Materials/methods: ASCs were cultured for four weeks in 2D, spheroids, Matrigel, or Bio-Blocks. Cultures were assessed for proliferation, senescence, apoptosis, trilineage differentiation, stem-like gene expression, secretome protein and extracellular vesicle (EV) production, and EV potency on endothelial cells (ECs).

Results: Bio-Block ASCs exhibited ~2-fold higher proliferation than spheroid and Matrigel groups, with senescence reduced 30-37% and apoptosis decreased 2-3-fold. Trilineage differentiation and stem-like markers (e.g. LIF, OCT4, IGF1) were significantly higher in Bio-Block ASCs. Secretome protein declined 35%, 47%, and 10% in 2D, spheroid, and Matrigel, respectively, but was preserved in Bio-Blocks. Similarly, EV production increased ~44% in Bio-Blocks, while other systems declined 30-70%. Bio-Block EVs enhanced EC proliferation, migration, and VE-cadherin expression, whereas spheroid EVs induced senescence and apoptosis.

Conclusion: This study highlights the critical influence of culture systems on scaling robust MSC-based therapies and introduces a biomimetic platform that represents a potential scalable strategy for producing high-potency and robust regenerative therapies.

Aims: This study aimed to enhance the osteoinductive potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) by integrating them into a nano-hydroxyapatite (nHAp)-enriched hydrogel scaffold for bone regeneration applications.

Materials & methods: EVs were isolated from naïve and osteogenically primed MSCs and characterized for morphology, cargo content, and cytocompatibility. Their uptake and osteoinductive activity were assessed in vitro using MC3T3 cells within a 3D interpenetrating network (IPN) hydrogel. The most effective EV formulation was incorporated into an nHAp - IPN hydrogel scaffold and evaluated both in vitro and in a murine subcutaneous implantation model.

Results: Primed MSC-EVs showed elevated calcium, ALP activity, and osteogenic/angiogenic mRNAs (Runx2, Vegf-a) compared to naïve EVs, with comparable size and morphology. Both EV types were internalized efficiently without cytotoxicity. In combination with nHAp, primed EVs enhanced ALP activity, calcium deposition, and in vivo mineralization. Histological analysis confirmed scaffold biocompatibility and mineralized tissue formation.

Conclusions: Osteogenically primed MSC-EVs significantly improved the osteoinductive performance of nHAp-based hydrogels, supporting their potential as a cell-free therapeutic strategy for bone tissue engineering.

Aims: Current treatments for demyelinating disorders focus on slowing progression but fail to repair damaged myelin. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -based technology has the potential to address key challenges in myelin repair by targeting genetic dysfunctions, modulating immune responses, and promoting oligodendrocyte differentiation. This systematic review aimed to evaluate CRISPR applications for myelin regeneration.

Methods: A comprehensive search of PubMed, Scopus, and other databases identified 48 studies. The included studies employed CRISPR in diverse experimental models, targeting genes associated with immune regulation and astrocyte activity, as well as correcting RNA splicing dysfunctions linked to neurodegeneration.

Results: CRISPR-edited stem cells showed significant potential in promoting myelin regeneration, with enhanced functional recovery in animal models of multiple sclerosis (MS). While most research focused on MS, promising applications were also observed in neuromyelitis optica spectrum disorder (NMOSD), such as reducing astrocytic damage via AQP4 targeting, and in progressive multifocal leukoencephalopathy (PML), where CRISPR disrupted JC polyomavirus replication.

Conclusions: Despite its promise, challenges remain. Future research should prioritize optimizing CRISPR delivery systems, expanding applications to underexplored disorders, and conducting long-term safety assessments. Early results are encouraging, but further studies are essential to translate preclinical success into clinical therapies.

Introduction: Biomimetics offers promising tools to improve wound healing in difficult clinical conditions. Polynucleotides (PN) show high potential for tissue repair in oral and periodontal surgery, by relying on the body's inherent self-healing capabilities. The aim of the present study was to elucidate in vitro the effects of Odonto-PN (O-PN) and Regenfast (REG), two PN-based compounds, on oral tissue repair.

Methods: We employed 3D spheroid cultures and cell scratch assays to simulate wound healing in vitro, assessing cell migration and morphology under normal conditions and following mitomycin-induced inhibition of cell growth.

Results: Both O-PN and REG supported early cell viability and spheroid disassembly. O-PN supported the initial outgrowth of fibroblasts, whereas REG enhanced sustained cell migration at later time points. In scratch assays, REG effectively facilitated defect closure - even under mitomycin treatment - and induced a more elongated, migratory cell phenotype.

Conclusions: These findings suggest that both O-PN and REG can favorably modulate fibroblast function to support wound repair. While O-PN fosters early activation and cell viability, REG exerts potent pro-migratory effects that may be particularly useful for complex periodontal regeneration. Their selective use could provide valuable adjuncts in clinical protocols aimed at restoring delicate oral structures, such as the interdental papillae.

Latest developments in the field of Advanced Therapy Medicinal Products and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in May 2025.

Despite the increasing visibility of the LGBTQ+ (Lesbian, Gay, Bisexual, Transgender, Queer, and other expansive genders or sexual orientations) community, LGBTQ+ persons continue to face significant barriers, discrimination, and stigmatization in the health care space. The unique challenges faced by LGBTQ+ persons in healthcare led bioethicists to develop queer bioethics. This approach to ethical reflection suggests that we should develop understanding of biomedical and biological topics related to LGBTQ+ persons and that we should examine topics not traditionally associated with LGBTQ+ persons through a queer lens. Here, we argue that queer bioethics provides valuable new perspectives for improving stem cell science. We examine specific issues that should be examined using a queer bioethical framework for the benefit of all persons and the overall advancement of stem cell science. We specifically address strategies for stem cell donation recruitment, creation of more comprehensive stem cell models for precision medicine, and the promotion of more inclusive practices for LGBTQ+ persons in the stem cell science workforce. We contend that these important and timely topics provide suitable starting points for applying a queer bioethical perspective to stem cell research and regenerative medicine. Furthermore, we underscore the importance of addressing these topics in the current political climate.