Regenerative Therapy最新文献

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, often leading to infertility due to anovulation. Recent advances suggest that endometrial stem cells (EnSCs) hold considerable promise for tissue regeneration, which could be pivotal in treating PCOS. To enhance the survival and stabilization of EnSCs within the ovary, the EnSCs were encapsulated in an injectable alginate/gelatin hydrogel (SC–H), which has excellent biocompatibility to support the survival of EnSCs. Polycystic ovary syndrome was induced in female Wistar rats using intraperitoneal injection of letrozole over 21 days. Then the rats were treated with SC, SC-H and clomiphene citrate for one-month post-PCOS induction. The effects of these treatments were evaluated based on changes in body and ovarian weights, inflammatory markers, endocrine profiles, and ovarian histology. The Induction of PCOS led to a significant increase in body and ovarian cyst weight, elevated serum levels of testosterone, luteinizing hormone (LH), and anti-Müllerian hormone (AMH), alongside reduced follicle-stimulating hormone (FSH) and progesterone levels. Histologically, there was a decrease in granulosa cells, immature follicles, and corpus luteum numbers. Treatment with SC and SC-H significantly mitigated these alterations, indicating improved PCOS conditions. Our findings demonstrate that SC and SC-H treatments can effectively ameliorate the symptoms of letrozole-induced PCOS in rats, primarily through their anti-inflammatory effects. This study lays the groundwork for potential clinical applications of EnSCs encapsulated in alginate/gelatin hydrogel as a novel therapeutic strategy for PCOS, highlighting the importance of biomaterials in stem cell-based therapies.

The development of diabetic foot ulcers is a common and severe complication of diabetes that can significantly affect quality of life. The physiological healing cascade does not progress tissue repair in diabetic foot ulcerations in a timely manner. Serum markers from foot ulcers have been used to characterize the healing process of the diabetic foot using various collection techniques. This study aimed to compare the use of cervical brushes and the Levine technique to collect wound fluid from foot ulcers of people with diabetes in order to determine the presence of cytokines. The collected material was used for gene expression analysis of macrophage/monocyte-associated cytokines IL1-β, IL-6, TNF-α, regulatory cytokine IL-10 and growth factor TGFβ, via quantitative polymerase chain reaction (qPCR). Both collection methods produced sufficient amounts of RNA, but significantly more RNA was collected using a cervical brush (brush 224.82 ng/μL vs. Levine 80.90 ng/μL p = 0.0001). Significantly higher levels of expression of the following cytokine genes were detected in samples collected using a cervical brush: IL1-β (p = 0.0001), IL-6 (p = 0.0106), IL-10 (p = 0.0277) and TGFβ (p = 0.0002). Understanding why some wounds are difficult to heal is important for developing more effective treatments, and biomarkers may be useful for predicting the healing trajectory. These results demonstrate that it is possible to collect material from the wound bed for RT-qPCR analysis, and the cervical brush proved to be a simple and rapid method for monitoring cytokine gene expression.

Platelet-rich plasma (PRP) is the portion of plasma with a platelet concentration above baseline that is recovered through centrifugation of autologous blood. PRP therapy is currently used for wound healing and pain relief in diverse medical fields. Although there have been recent reports of adverse events (AEs) possibly related to PRP treatment, the safety profile of PRP treatment remains unclear. Therefore, this review discusses the risks inherent in PRP therapy and the current issues by surveying reports on AEs associated with PRP treatment within different fields.

PubMed was searched for research articles referring to AEs associated with PRP therapy from inception to January 2024. Literature survey revealed that PRP therapy may involve several AEs, including postoperative infections, blindness, inflammation, allergic reactions, and nodule development. The most commonly reported AE was postoperative infections. Since PRP therapy generally proceeds in the process of blood collection, manufacturing, and administration to patients, it is conjectured that PRP may have been contaminated with microorganisms at some point in this series of processes, leading to bacterial infection. Additionally, because PRP cannot be sterilized like pharmaceuticals, it is important to prevent microbial contamination during each PRP treatment process. However, the specific process that involves the risk of microbial contamination remains unclear. To take measures to prevent microbial contamination of PRP, it may be necessary to elucidate the risk factors for microbial contamination during PRP treatment. It may be important to elucidate the effectiveness and risks of PRP therapy as well as to establish a follow-up system after PRP treatment. Currently, most reports of AEs related to PRP therapy are case reports; therefore, the accumulation of high-quality evidence and detailed verification are necessary to determine the causal relationship between PRP therapy and each AE.

Tendon injury is a common disorder of the musculoskeletal system, with a higher possibility of occurrence in elderly individuals and athletes. After a tendon injury, the tendon suffers from inadequate and slow healing, resulting in the formation of fibrotic scar tissue, ending up with inferior functional properties. Therapeutic strategies involving the application of growth factors have been advocated to promote tendon healing. Growth and differentiation-5 (GDF-5) represents one such factor that has shown promising effect on tendon healing in animal models and in vitro cultures. Although promising, these studies are limited as the molecular mechanisms by which GDF-5 exerts its effect remain incompletely understood. Starting from broadly introducing essential elements of current understanding about GDF-5, the present review aims to define the effect of GDF-5 and its possible mechanisms of action in tendon healing. Nevertheless, we still need more in vivo studies to explore dosage, application time and delivery strategy of GDF-5, so as to pave the way for future clinical translation.

Gene therapies, which include viral-vector gene delivery, genome editing, and genetically modified cell therapy, are innovative treatments with the potential to address the underlying genetic causes of disorders and to provide life-changing value in terms of curing disease. Although adeno-associated virus (AAV)-based gene therapy is one of the most advanced types of gene therapy, far fewer AAV-based gene therapy studies have been conducted in Asia than in North America and Europe. The 6th Asia Partnership Conference of Regenerative Medicine (APACRM) was held on April 20, 2023 in Tokyo, Japan. APACRM Working Group 3 comprehensively analyzed the regulatory processes that occur prior to the initiation of clinical trials as well as the regulatory requirements for AAV-based gene therapies for six Asian countries or regions (China, India, Japan, Singapore, South Korea, and Taiwan). In this article, we report the outcomes of this conference, summarizing the regulatory requirements for initiating clinical trials for AAV-based gene therapies in terms of the laws, regulations, and guidelines for gene therapy; consultations or reviews required by the health authorities; points to consider for scientific reviews by the health authorities; and specific challenges to address when developing gene therapy products in these locations. Finally, we present several policy recommendations, including simplifying the regulatory review system for multiple scientific review areas; simplifying the regulatory consultation system; and providing training programs and regulatory guidance to support the advancement of gene therapy development in Asia.

Objectives

Adipose-derived stem cells (ADSCs) are widely used in wound care because they release a variety of cytokines. However, the molecular mechanism of paracrine action remains unclear. It has been reported that basic fibroblast growth factor (bFGF) enhances the therapeutic potential of ADSCs. In this study, we searched for cytokines whose release from ADSCs is enhanced by bFGF stimulation.

Results

Quantitative RT-PCR and ELISA analyses revealed that bFGF upregulates CXCL-1 and IL-8 mRNA synthesis and secretion from ADSCs. Both cytokines showed the ability to promote important processes for wound healing, including tube formation of vascular and lymphatic endothelial cells and cell migration of fibroblasts in vitro.

Conclusions

These results suggest that bFGF stimulation increases the secretion of CXCL-1 and IL-8 from ADSCs and that these cytokines may promote angiogenesis, lymphangiogenesis, and cell migration, leading to enhanced efficiency of wound healing.

Background

To overcome organ shortage during transplantation, interspecies organ generation via blastocyst complementation has been proposed, although not yet in evolutionarily distant species. To establish high levels of chimerism, low chimerism is required early in development, followed by high chimerism, to effectively complement the organ niche. Very few human cells are expected to contribute to chimerism in heterologous animals. Previous studies had demonstrated increased donor chimerism in both intra- and interspecies chimeras in rodents, using insulin-like growth factor 1 receptor (Igf1r) knockout (KO) mice; deletion of the Igf1r gene in the mouse host embryo created a cell-competitive niche. The current study aimed to generate IGF1R–KO pigs and evaluate whether they have the same phenotype as Igf1r-KO mice.

Methods

To generate IGF1R–KO pigs, genome-editing molecules were injected into the cytoplasm of pig zygotes. The fetuses were evaluated at 104 days of gestation.

Results

IGF1R–KO pigs were generated successfully. Their phenotypes were almost identical to those of Igf1r-KO mice, including small lungs and enlarged endodermal organs in fetuses, and they were highly reproducible.

Conclusions

Pigs may allow the generation of organs using blastocyst complementation with developmentally-compatible xenogeneic pluripotent stem cells over a large evolutionary distance.