Porous scaffold for mesenchymal cell encapsulation and exosome-based therapy of ischemic diseases

Autor: Andreas Czosseck, Max M. Chen, Helen Nguyen, Annette Meeson, Chuan-Chih Hsu, Chien-Chung Chen, Thomashire A. George, Shu-Chian Ruan, Yuan-Yuan Cheng, Po-Ju Lin, Patrick C.H. Hsieh, David J. Lundy
Rok vydání: 2022
Předmět:
Zdroj: Journal of Controlled Release. 352:879-892
ISSN: 0168-3659
Popis: Ischemic diseases including myocardial infarction (MI) and limb ischemia are some of the greatest causes of morbidity and mortality worldwide. Cell therapy is a potential treatment but is usually limited by poor survival and retention of donor cells injected at the target site. Since much of the therapeutic effects occur via cell-secreted paracrine factors, including extracellular vesicles (EVs), we developed a porous material for cell encapsulation which would improve donor cell retention and survival, while allowing EV secretion. Human donor cardiac mesenchymal cells were used as a model therapeutic cell and the encapsulation system could sustain three-dimensional cell growth and secretion of therapeutic factors. Secretion of EVs and protective growth factors were increased by encapsulation, and secreted EVs had hypoxia-protective, pro-angiogenic activities in in vitro assays. In a mouse model of limb ischemia the implant improved angiogenesis and blood flow, and in an MI model the system preserved ejection fraction %. In both instances, the encapsulation system greatly extended donor cell retention and survival compared to directly injected cells. This system represents a promising therapy for ischemic diseases and could be adapted for treatment of other diseases in the future.
Databáze: OpenAIRE