Researchers from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences and Beijing Chaoyang Hospital have developed a new "pseudo cell" formulation based on self-healing microcapsule-loading exosomes to address a range of vitreoretinal diseases.
Published on October 23 in Nature Biomedical Engineering, the study addresses vitreoretinal diseases, a diverse group of vision-threatening diseases that often lead to irreversible vision loss.
Current clinical treatments for these diseases are typically unsatisfactory and come with various side effects, often requiring frequent and inconvenient follow-up treatments, impacting patient compliance.
In recent years, researchers have explored cell-based therapy for ophthalmology. Despite some promising results, challenges such as low cell-survival rates, unstable cell phenotypes, and strict storage conditions have hindered the clinical feasibility of cell-based approaches.
The therapeutic advantages of numerous cell types are attributed to paracrine mechanisms. As a result, investigators have investigated the potential use of more stable cell-secreted components, like exosomes, as therapeutic agents for managing ocular diseases. In line with this, scientists from IPE and Beijing Chaoyang Hospital have introduced a "pseudo cell" formulation platform.
Construction of ExoCap and therapeutic effects of MExoCap or TrExoCap in RIRI or PMU mouse model, respectively. Credit: Bao Han and Tian Ying
In this innovative platform, exosomes extracted from cells were encapsulated within self-healing microcapsules known as ExoCaps. Professor Ma Guanghui from IPE explained that these ExoCaps mimic functional cells in terms of their size, internal structure, and secretion behavior.
Following intravitreal injection, the ExoCaps localized to the lower region of the vitreous cavity. This strategic placement prevented the occurrence of blurred vision, a common side effect of suspending live cells within the vitreous cavity. Additionally, as the microcapsules gradually degraded over the course of a month, exosomes were released incrementally, offering the potential for sustained therapeutic benefits.
By employing models of retinal ischemia-reperfusion injury (RIRI) and primed mycobacterial uveitis (PMU), the scientists observed positive therapeutic effects resulting from the utilization of two distinct ExoCap formulations. These formulations were developed by microencapsulating exosomes derived from mesenchymal stem cells (MExo) and regulatory T cells (TrExo). Professor Wei Wei from IPE emphasized the flexibility of the ExoCap platform, which can accommodate exosomes from diverse cellular sources to address a range of therapeutic requirements.
Therapeutic effects of TrExoCap in a PMU nonhuman primate model. Credit: Bao Han and Tian Ying
Prof. Tao Yong from Beijing Chaoyang Hospital said: “This study is still at the preclinical stage. Given that exosomes are natural vesicles produced from endogenous cells with good biocompatibility and the microcapsule material [poly(lactic-co-glycolic acid)] has been approved for clinical use, ExoCap has the potential for translation to the clinic.”
Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases, Nature Biomedical Engineering (2023). DOI: 10.1038/s41551-023-01112-3