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

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

doi:10.1016/j.jconrel.2022.10.057

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

J Control Release. 2022 Dec:352:879-892. doi: 10.1016/j.jconrel.2022.10.057. Epub 2022 Nov 14.

Authors

Affiliations

¹ Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
² Biosciences Institute, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom.
³ Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan.
⁴ Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan; International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
⁵ International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan.
⁶ Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
⁷ Graduate Institute of Biomedical Materials & Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan; International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan; Center for Cell Therapy, Taipei Medical University Hospital, Taipei 110, Taiwan. Electronic address: dlundy@tmu.edu.tw.

PMID: 36370875
DOI: 10.1016/j.jconrel.2022.10.057

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Encapsulation
Disease Models, Animal
Exosomes* / metabolism
Extracellular Vesicles* / metabolism
Humans
Ischemia / therapy
Mesenchymal Stem Cells* / metabolism
Mice
Myocardial Infarction* / metabolism
Myocardial Infarction* / therapy
Porosity