Inter-synergized neuroprotection of costunolide engineered bone marrow mesenchymal stem cells targeting system.
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| Abstract |
Treatment of stroke remains difficult due to the unsatisfactory or unlocalized delivery of small molecule- and cell-based therapeutics in injured brain tissues. This is particularly the case for costunolide (Cos), which is highly neuroprotective and anti-inflammatory but finds great difficulty in reaching the brain. Here, we present that Cos induces the differentiation of bone marrow mesenchymal stem cells (bMSCs) into glia-like cells (C-bMSCs) capable of secreting neurotrophic factors and homing to injured brain tissues. By taking advantage of the homing effect, Cos and C-bMSCs were simultaneously funneled into the damaged brain by: (i) preparing Cos micelles (Cos-M) through entrapping Cos into the amphiphilic copolymer mPEG-PLGA [poly(ethylene oxide) monomethyl ether-poly(lactide-co-glycolide)], and (ii) incorporating Cos-M into C-bMSCs to give an intravenously injectable cell-like composite termed Cos@C-bMSCs, which displayed the inter-synergized neuroprotective efficacy in the cerebral ischemia reperfusion (CIR) injured rats. As desired, in the injured brain area, Cos@C-bMSCs simultaneously released Cos and C-bMSCs (glia-like cells) to repair the injured brain and to secret neurotrophic factors such as nerve growth factor (NGF). In view of the availability and reliability of autologous MSCs, the proof-of-concept design, development, and in vivo efficacy of Cos@C-bMSCs signify a movement in our management of brain damages.
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| Authors | Zhiyuan Mao, Yang Liu, Xiaojing Lv, Yu Jiang, Qun Zhang, Li Yang, Hezhong Jiang, Renxiang Tan, Rui Tan |
| Journal | International journal of pharmaceutics (Int J Pharm) Vol. 639 Pg. 122823 (May 25 2023) ISSN: 1873-3476 [Electronic] Netherlands |
| PMID | 36921741 (Publication Type: Journal Article) |
| Copyright | Copyright © 2023. Published by Elsevier B.V. |
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