Regenerative medicine最新文献

Aim: To systematically identify best current evidence on intra-articular combination therapy with hyaluronic acid (HA) and platelet-rich plasma (PRP), compared to monotherapy in knee osteoarthritis.

Methods: Using the McMaster University and National Health Service five-step systematic approach, we conducted a bottom-up literature search of all existing evidence through Ovid Medline, Ovid Embase, and Cochrane (Central - Wiley) from January 2021 to June 2024.

Results: Of 258 articles retrieved, we systematically narrowed best current evidence to one meta-analysis when evaluating combination therapy versus HA alone. This demonstrated superior outcomes with combination therapy against HA only at 3, 6, and 12 months on the visual acuity scale (VAS, p < 0.001), and with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 12 months in areas of stiffness and physical function (p < 0.001). For combination therapy versus PRP alone, one randomized controlled trial qualified as best current evidence. This demonstrated superior VAS outcomes with combination therapy compared to PRP monotherapy at 6 months (p < 0.02).

Conclusion: Best current evidence indicates that intra-articular HA and PRP as combination therapy has superior short and long term symptom control over HA or PRP as monotherapy. Due to the extensive heterogeneity in the studies, results should be interpreted with caution.

Extracellular Vesicles (EVs) became a focus of clinical research when experimental and pre-clinical studies showed that they mimic their parent cells' regenerative and therapeutic effects and their cargo carries disease-specific diagnostic and prognostic biomarkers. Since the publication of data forms an endpoint of the study, this review specifically focused on the published clinical trials done with EVs. For brevity, this review was restricted to the last 10 years. Unexpectedly, the literature search showed that very few clinical trials assessing the therapeutic applications of EVs were published in this period indicating that they have not reached their desired endpoint. Conversely, most studies showed the potential of EVs present in various biofluids as a promising source of diagnostic and prognostic biomarkers for various diseases, and predictive markers to assess the effectiveness of therapy. This stark difference in the numbers could perhaps be due to the time-consuming regulatory processes involved in the clinical-grade preparation and characterization of EVs, and the determination of their safety and effective dose regimens. One wonders whether fast-tracking regulatory affairs could help accelerate the therapeutic use of EVs. This aspect needs urgent attention.

Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions in September 2024.

Peripheral nerve injuries lead to severe functional impairments, with rodent models essential for studying regeneration. This review examines key factors affecting outcomes. Age-related declines, like reduced nerve fiber density and impaired axonal transport of vesicles, hinder recovery. Hormonal differences influence regeneration, with BDNF/trkB critical for testosterone and nerve growth factor for estrogen signaling pathways. Species and strain selection impact outcomes, with C57BL/6 mice and Sprague-Dawley rats exhibiting varying regenerative capacities. Injury models - crush for early regeneration, chronic constriction for neuropathic pain, stretch for traumatic elongation and transection for severe lacerations - provide insights into clinically relevant scenarios. Repair techniques, such as nerve grafts and conduits, show that autografts are the gold standard for gaps over 3 cm, with success influenced by graft type and diameter. Time course analysis highlights crucial early degeneration and regeneration phases within the first month, with functional recovery stabilizing by three to six months. Early intervention optimizes regeneration by reducing scar tissue formation, while later interventions focus on remyelination. Understanding these factors is vital for designing robust preclinical studies and translating research into effective clinical treatments for peripheral nerve injuries.

Aims: The UK advanced therapy medicinal product (ATMP) clinical trials database, produced annually by CGT Catapult, aims to assess the progress and state of the UK ATMP clinical development landscape. The aim of this article is to highlight key findings from the database and put them into context within the global landscape and various initiatives intended to attract ATMP developers to the UK.

Method: A targeted search of GlobalData's clinical trial database was performed, followed by refinement so that only trials investigating products meeting ATMP definitions were included, and that each trial was only counted once in the analysis.

Results: The 2023 data show that the number of ongoing ATMP clinical trials in the UK has remained approximately static, in contrast to a 10% reduction reported globally. Approximately 80% of these trials were commercially sponsored. Although most ATMP clinical trials are early phase, there is evidence indicating progression to later phase studies.

Conclusion: The data indicate that the UK remains an attractive region for ATMP clinical trials. Factors including UK government investment in research, regulatory support offered by MHRA, and the Advanced Therapy Treatment Centre (ATTC) network of clinical sites, may contribute to the positive ecosystem available to developers of ATMPs.

Background: To address the limitations of Cultivated Limbal Epithelial Transplantation (CLET) and the use of amniotic membrane (AM) in treating Limbal Stem Cell Deficiency (LSCD), we aimed to develop a Collagen/Silk Fibroin (Co/SF) scaffold enriched with Platelet-Rich Growth Factor (PRGF) to support the proliferation, maintenance, and differentiation of Wharton's jelly-derived mesenchymal stem cells (WJMSCs) into corneal epithelial cells (CECs).

Method: Scaffolds loaded with PRGF were evaluated through release studies, cytotoxicity assays, and cell differentiation. The proliferation and differentiation of WJMSCs and Limbal Epithelial Stem Cells (LESCs) were investigated using MTT assays, real-time PCR and immunostaining.

Results: The PRGF-loaded Co/SF scaffold significantly promoted the proliferation of both WJMSCs and LESCs in a concentration-dependent manner. Real-time PCR and immune staining revealed a significant increase in the expression of P63, ABCG2, and cytokeratin 3/12 markers in WJMSCs, a significant decrease in the expression of P63 and ABCG2, and a significant increase in the expression of cytokeratin 3/12 markers indicating successful differentiation into CECs.

Conclusion: The WJMSC cultured on PRGF-enriched Co/SF scaffold demonstrates potential as a viable alternative to conventional CLET, offering a promising strategy for corneal tissue regeneration.

There is a paucity of data regarding using platelet-rich plasma therapy for Baker's cyst-associated medial meniscal tear. To date, conservative treatments for this type of condition include aspiration of fluid effusion with steroid injection and physical therapy. When this treatment fails, arthroscopic debridement, meniscectomy, cyst decompression and open cystectomy are available surgical management options. Recurrence rates, however, are high such that even these procedures fail to provide long-term pain relief. This case study explores the benefits of leukocyte-rich platelet-rich plasma therapy in treating tears in the posterior horn of the medial meniscus with concomitant Baker's cyst. With limited studies available, this case hopes to encourage more studies to be done in the future to provide a conservative option for patients with similar cases.