Regenerative medicine最新文献

Background: Rheumatoid arthritis (RA) is categorized as an autoimmune condition. Bone marrow-derived mesenchymal stromal cell (BMSC) derived exosome (BMSC-Exo) exert vital character in RA. We aimed to investigate the regulatory mechanism of BMSC-Exo in alleviating RA.

Methods: BMSC was isolated from mouse bone marrow. Collagen-induced arthritis (CIA) was induced by injecting bovine type II collagen and complete Freund's adjuvant. Arthritis score, incidence, and withdrawal threshold were assessed. Hematoxylin-eosin staining was used to observe knee joint damage. CD4⁺ T cells were isolated from the spleen, and T helper 17 (Th17) proportions were measured by flow cytometry. Caspase-1 activity was assessed.

Results: BMSC-Exo injection reduced arthritis score and incidence of arthritis, and elevated the withdrawal threshold of CIA mice. BMSC-Exo also alleviated knee damage in CIA mice and reduced the Th17 proportion. BMSC-Exo down-regulated inflammatory cytokine levels, as well as caspase-1 activity. BMSC-Exo up-regulated PR Domain Zinc Finger Protein 1 (PRDM1) levels. PRDM1 knockdown in BMSC down-regulated PRDM1 expression in Exo but did not affect up-regulated PRDM1 expression in CD4⁺ T cells. In vivo, BMSC-Exo affected RA pathology by acting on PRDM1.

Conclusions: BMSC-Exo improved RA by promoting PRDM1 expression in CD4⁺ T cells and inhibiting Th17 cell differentiation.

The expanding regenerative medicine toolkit is reaching a record number of lives. There is a pressing need to enhance the precision, efficiency, and effectiveness of regenerative approaches and achieve reliable outcomes. While regenerative medicine has relied on an empiric paradigm, availability of big data along with advances in informatics and artificial intelligence offer the opportunity to inform the next generation of regenerative sciences along the discovery, translation, and application pathway. Artificial intelligence can streamline discovery and development of optimized biotherapeutics by aiding in the interpretation of readouts associated with optimal repair outcomes. In advanced biomanufacturing, artificial intelligence holds potential in ensuring quality control and assuring scalability through automated monitoring of process-critical variables mandatory for product consistency. In practice application, artificial intelligence can guide clinical trial design, patient selection, delivery strategies, and outcome assessment. As artificial intelligence transforms the regenerative horizon, caution is necessary to reduce bias, ensure generalizability, and mitigate ethical concerns with the goal of equitable access for patients and populations.

Aims: This phase I trial assessed the safety and potential efficacy of monthly 3 dose intravenous infusion of allogeneic bone marrow-derived clonal mesenchymal stromal cells (BM-cMSCs) in refractory rheumatoid arthritis (RA) patients over 24 weeks.

Patients & methods: Six patients with refractory RA received BM-cMSC infusions at one-month intervals over a 24-week period. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Clinical efficacy was assessed using the Visual Analog Scale (VAS), Simple and Clinical Disease Activity Indices (SDAI/CDAI), Health Assessment Questionnaire (HAQ), and American College of Rheumatology (ACR) response criteria. Serological makers including: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IL-10, IL-17, TNF-α, and Treg/Th17 ratios were measured.

Results: BM-cMSC infusions were well-tolerated, with no SAEs reported. VAS scores improved in three patients, with two achieving sustained pain relief and quality-of-life enhancement. Four patients met ACR20 at week 16, while SDAI and CDAI scores indicated disease activity reduction in three patients. Anti-CCP and RF levels showed variable responses, with some increases not consistently correlating with clinical outcomes. Serological biomarkers showed mixed results; IL-10 increased in five patients, while pro-inflammatory markers TNF-α and IL-17 decreased in the same individuals.

Conclusions: BM-cMSC therapy demonstrated a favorable safety profile and potential efficacy in managing refractory RA. While preliminary results are promising, further studies with larger cohorts and long-term follow-up are needed to validate these findings and optimize therapeutic strategies.

Clinical trial registration: IRCT20080728001031N29.

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 August 2024.

Stem cell research is currently undergoing a promising transformation from primarily basic research to increasing emphasis on translation and clinical trials. To reach patients, however, stem cell treatments need to be not only technically but also economically viable. In this commentry we present insights into emerging pricing models that may help ensure access to advanced and expensive treatments like stem cell therapies. Further, we present some reflections on the practical and ethical challenges that these models involve. We provide this information to allow the field of translational stem cell research to think ahead and to raise awareness of the outstanding social and ethical issues.

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.