bims-engexo 2025-03-09 papers

Adv Healthc Mater. 2025 Mar 05. e2405126

pH-Responsive Engineered Exosomes Enhance Endogenous Hyaluronan Production by Reprogramming Chondrocytes for Cartilage Repair.

Xiaodan Wu, Weiyong Tao, Ziyang Lan, Yaping Tian, Zhenyu Zhong, Jianwei Wang, Jiaqi Li, Xulong Liu, Xin Zhang, Yifan Wang, Jianglin Wang, Bin Zhang, Yingying Du, Shengmin Zhang.

Trauma or inflammation-caused cartilage injury leads to joint dysfunction and pain. Exogenous hyaluronic acid (HA) injection is a well-established treatment, but it has a short duration in vivo and requires multiple injections. Here, a new strategy for in situ reprogramming chondrocytes to continuously produce endogenous high molecular weight HA is developed. This involves a pH-responsive engineered exosome decorated with vesicular stomatitis virus glycoprotein (VSV-G) and hyaluronan synthase type 2 (HAS2). Such engineered exosomes successfully deliver HAS2 to the chondrocyte membranes via VSV-G-mediated membrane fusion triggered by low pH, rather than being degraded in lysosomes. This results in the generation of HAS2-chondrocytes, which are characterized to produce high molecular weight HA in vitro and in vivo. With increased endogenous HA, the injected engineered exosomes enhance cartilage regeneration and inhibit osteoarthritis (OA) progression. Notably, one-shot administration of engineered exosomes drastically increases the intra-articular concentration of high molecular weight HA to 145% of the exogenous HA injection group. Importantly, such endogenous HA is sustained for 4 weeks, whereas the injected exogenous HA rapidly decreases within 2 weeks. The findings demonstrate that pH-responsive engineered exosomes capable of generating endogenous HA hold great potential to replace the treatment of multiple injections of exogenous HA for cartilage repair.

Keywords: bioactive materials; cartilage repair; endogenous hyaluronan; pH‐responsive engineered exosomes; vesicular stomatitis virus glycoprotein

DOI: https://doi.org/10.1002/adhm.202405126

ACS Nano. 2025 Mar 05.

Genetically Engineered Stromal Cell Exosomes from High-Throughput Herringbone Microfluidics.

Junjie Huang, Hanxu Chen, Zhiqiang Luo, Min Nie, Jinglin Wang, Ling Lu, Yuanjin Zhao.

Stromal cell-derived exosomes have demonstrated their value in the field of biomedical engineering. However, the low production and specific requirements of different diseases limited the practical efficacy of these exosomes and restricted their wider applications. Here, we presented a method to culture genetically engineered mesenchymal stromal cells (MSC) that overexpressed the hepatocyte growth factor (HGF) in microfluidics and harvest mass HGF overexpressed exosomes for wound healing. The microfluidic chips were featured with herringbone grooves and micropillar arrays, where sufficient fluidic mechanical stimuli and efficient nutrient delivery were promoted by a turbulent vortex. It was demonstrated that the production of exosomes was much higher than by the traditional flask cell culture, along with higher HGF content. In addition, the MSCHGF-secreted exosomes were applied for wound healing in diabetic rat model, showing superior angiogenesis, cell migration, and immune modulation capabilities. These features indicated that the genetically engineered MSCHGF exosomes from high-throughput herringbone microfluidics possess great potential for wound healing and related biomedical applications.

Keywords: MSC; exosome; genetic engineering; microfluidics; wound healing

DOI: https://doi.org/10.1021/acsnano.5c01773

IBRO Neurosci Rep. 2025 Jun;18 323-337

Exploring the roles and clinical potential of exosome-derived non-coding RNAs in glioma.

Peng Jin, Xue Bai.

Non-coding accounts for 98 %-99 % of the human genome and performs many essential regulatory functions in eukaryotes, involved in cancer development and development. Non-coding RNAs are abundantly enriched in exosomes, which play a biological role as vectors. Some biofunctional non-coding RNAs are specifically designed as exosomes for the treatment of cancers such as glioma. Glioma is one of the most common primary tumors within the skull and has varying degrees of malignancy and histologic subtypes of grades I-IV. Gliomas are characterized by high malignancy and an abundant blood supply due to rapid cell proliferation and vascularization, often with a poor prognosis. Exosomal non-coding RNAs can be involved in the tumorigenesis process of glioma from multiple directions, such as angiogenesis, tumor proliferation, metastatic invasion, immune evasion, apoptosis, and autophagy. Therefore, non-coding RNAs in exosomes are suitable as markers or therapeutic targets for early diagnosis of diseases and for predicting the prognosis of a variety of diseases. Regulating exosome production and the level of exosomal non-coding RNA expression may be a new approach to prevent or eliminate glioma. In this review, we review the origin and characteristics of exosomal non-coding RNAs, and introduce the functional studies of exosomal non-coding RNAs in glioma and their potential clinical applications, in order to broaden new ideas for the treatment of glioma.

Keywords: Biomarkers; Exosomes; Glioma; RNA; Signaling transduction

DOI: https://doi.org/10.1016/j.ibneur.2025.01.015

Int J Periodontics Restorative Dent. 2025 Mar 07. 0(0): 1-20

Exosome-Mediated Alveolar Ridge Augmentation: A First Human Case Report with Histology.

Nathan Estrin, Nima Farshidfar, Paras Ahmad, Scott Froum, Marco Antonio Castro Pinto, Yufeng Zhang, Richard J Miron.

Exosomes, the smallest subset of extracellular vesicles, play a crucial role in cell signaling and communication throughout the body. Their regenerative potential has sparked tremendous interest, with over 5,000 articles on exosomes being published yearly, primarily focused on invitro and pre-clinical studies. However, to date, no study has investigated their use in humans for dental applications. In this first case report, horizontal ridge augmentation was performed utilizing a novel combination of bone allografts, platelet-rich fibrin (PRF), and a specialized subset of exosomes (Periosomes). Implants were placed at 3 months post-surgery, during which a core biopsy was taken for histological analysis. Additionally, cone-beam computed tomography (CBCT) scans were obtained at 1, 2, 3, and 6 months, revealing marked and progressive bone growth. To our knowledge, this study represents the first documented use of exosomes in human alveolar bone regeneration. This case highlights the promising potential of exosomes in regenerative dentistry, opening new avenues for their application in guided bone regeneration procedures.

Keywords: Alveolar ridge augmentation; Exosomes; Guided tissue regeneration; Leukocyte and Plateletrich fibrin; bone morphogenetic protein; extracellular vesicles

DOI: https://doi.org/10.11607/prd.7567