Study: “Pseudo cell” formulation targets vitreoretinal disease

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A team of scientists from the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences and Beijing Chaoyang Hospital have come up with a new “pseudo cell” formulation based on self-healing microcapsule-loading exosomes to treat diverse vitreoretinal diseases.

The study was published this month in Nature Biomedical Engineering.¹

By targeting vitreoretinal diseases, the researchers are tackling a range of vision-threatening disorders which often result in severe irreversible vision loss. The efficacy of current treatments for vitreoretinal diseases in clinic is generally ineffective and treatments often cause several side effects. Frequently repeated treatments often are needed, which can result in poor patient compliance.

Researchers have delved into the possibility of cell-based therapy in ophthalmology. Despite some positive results, cell-based therapeutics in ophthalmology have encountered a series of problems, such as low cell-survival rates, instability of cell phenotype and the need for strict storage conditions, which have limited the clinical feasibility of these cell-based technologies.¹

“The therapeutic benefits of many cell types involve paracrine mechanisms. Inspired by the paracrine functions of exosomes and the sustained degradation properties of microcapsules, here we report the therapeutic benefits of exosome-loaded degradable poly(lactic-co-glycolic acid) microcapsules with micrometric pores for the treatment of vitreoretinal diseases,” the researchers wrote in the study.

After the intravitreal injection in a mouse model of retinal ischaemia-reperfusion injury, microcapsules encapsulating mouse mesenchymal-stem-cell-derived exosomes settled in the inferior vitreous cavity, released exosomes for over one month as they underwent degradation and led to the restoration of retinal thickness to nearly that of the healthy retina.¹

“In mice and non-human primates with primed mycobacterial uveitis, intravitreally injected microcapsules loaded with exosomes from monkey regulatory T cells resulted in a substantial reduction in the levels of inflammatory cells,” the researchers wrote in the study. “The exosome-encapsulating microcapsules, which can be lyophilised, may offer alternative treatment options for vitreoretinal diseases.”

According to a Chinese Academy of Sciences (CAS) news release,² the therapeutic benefits of many cell types are known to involve paracrine mechanisms. As a result, researchers have explored the possibility of using more stable cell-secreting components (such as exosomes) as therapeutic components to treat ocular diseases. With this in mind, the researchers from IPE and Beijing Chaoyang Hospital have proposed a "pseudo cell" formulation platform, according to the release.

In this platform, exosomes isolated from cells were loaded into self-healing microcapsules, called ExoCaps.¹

“ExoCaps simulate functional cells in terms of size, internal structure, and secretion behavior,” MA Guanghui, PhD, a scientist from IPE, said in the CAS news release.

Following the intravitreal injection, ExoCaps ended up in the inferior area of the vitreous cavity, according to the researchers Since blurred vision can be induced by suspension of living cells in the vitreous cavity, having the ExoCaps settle in the inferior area made it possible to avoid blurry vision. The exosomes were gradually released as the microcapsules degraded over a month, paving the way for a long-term therapeutic effect.²

The researchers used retinal ischemia-reperfusion injury (RIRI) and primed mycobacterial uveitis (PMU) models to detect therapeutic benefits from the application of two different ExoCap formulations, based on microencapsulation of mesenchymal stem cell-derived exosomes (MExo) and Treg cell-derived exosomes (TrExo), respectively.

"Our ExoCap platform is flexible and can load exosomes of different cellular origins to meet varied therapeutic needs," Wei Wei, PhD, a scientist with IPE, said in the news release.

Moreover, the researchers were able to verify potent therapeutic efficacies in both murine and nonhuman primate models of vitreoretinal diseases.¹

"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,” sTao Yong, MD, director of Beijing Chaoyang Hospital’s ophthalmology department, said the CAS news release. “ExoCap has the potential for translation to the clinic.” 

REFERENCE

1. Bao, H., Tian, Y., Wang, H. et al. Exosome-loaded degradable polymeric microcapsules for the treatment of vitreoretinal diseases. Nat. Biomed. Eng (2023). https://doi.org/10.1038/s41551-023-01112-3

2. Scientists develop ‘psuedo cell’ formulation for vitreoretinal disease therapy. Eurekalert! Published October 23, 2023. Accessed October 25, 2023. https://www.eurekalert.org/news-releases/1005387