@article{518264df71c849099653fbc12883d73f,
title = "Porous scaffold for mesenchymal cell encapsulation and exosome-based therapy of ischemic diseases",
abstract = "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.",
keywords = "Cardiac patch, Cell encapsulation, Cell therapy, Exosome, Extracellular vesicle, Ischemic disease, Limb ischemia, Myocardial infarction",
author = "Andreas Czosseck and Chen, {Max M.} and Helen Nguyen and Annette Meeson and Chuan-Chih Hsu and Chien-Chung Chen and George, {Thomashire A.} and Shu-Chian Ruan and Yuan-Yuan Cheng and Po-Ju Lin and Hsieh, {Patrick C.H.} and Lundy, {David J.}",
note = "Funding Information: The authors thank Academia Sinica Cryo Electron Microscope Core Facility (ASCEM) for providing cryoEM images. We thank TMU LAC for technical support of IVIS and mouse blood tests. We thank TMU instrument core facility for use of Stellaris, TissueFAXS and NTA. Work was supported by Taiwan Ministry of Science and Technology (MOST), grant 109-2636-B-038-003, which was awarded to David J. Lundy. Funding Information: The authors thank Academia Sinica Cryo Electron Microscope Core Facility (ASCEM) for providing cryoEM images. We thank TMU LAC for technical support of IVIS and mouse blood tests. We thank TMU instrument core facility for use of Stellaris, TissueFAXS and NTA. Work was supported by Taiwan Ministry of Science and Technology (MOST), grant 109-2636-B-038-003 , which was awarded to David J. Lundy. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = dec,
doi = "10.1016/j.jconrel.2022.10.057",
language = "English",
volume = "352",
pages = "879--892",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier B.V.",
}
