Mesenchymal stem cell-derived magnetic extracellular nanovesicles for targeting and treatment of ischemic stroke

Han Young Kim; Tae Jung Kim; Lami Kang; Young-Ju Kim; Min Kyoung Kang; Jonghoon Kim; Ju Hee Ryu; Taeghwan Hyeon; Byung-Woo Yoon; Sang-Bae Ko; Byung-Soo Kim

doi:10.1016/j.biomaterials.2020.119942

Mesenchymal stem cell-derived magnetic extracellular nanovesicles for targeting and treatment of ischemic stroke

Biomaterials. 2020 Jun:243:119942. doi: 10.1016/j.biomaterials.2020.119942. Epub 2020 Mar 6.

Authors

Affiliations

¹ Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
² Department of Neurology, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
³ School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea; Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea.
⁴ Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
⁵ Department of Neurology, Seoul National University Hospital, Seoul, 03080, Republic of Korea. Electronic address: sangbai1378@gmail.com.
⁶ School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea; Interdisciplinary Program of Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea; Institute of Chemical Processes, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address: byungskim@snu.ac.kr.

PMID: 32179302
DOI: 10.1016/j.biomaterials.2020.119942

Abstract

Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke.

Keywords: Exosomes; Extracellular nanovesicles; Iron oxide nanoparticles; Ischemic stroke; Mesenchymal stem cells.

Publication types

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

MeSH terms

Animals
Brain Ischemia* / therapy
Disease Models, Animal
Ischemic Stroke*
Magnetic Phenomena
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stem Cells*
Rats
Stroke* / therapy