Inter-synergized neuroprotection of costunolide engineered bone marrow mesenchymal stem cells targeting system

• Published in: International journal of pharmaceutics 2023-05, Vol.639, p.122823-122823, Article 122823
• Main Authors: Mao, Zhiyuan, Liu, Yang, Lv, Xiaojing, Jiang, Yu, Zhang, Qun, Yang, Li, Jiang, Hezhong, Tan, Renxiang, Tan, Rui
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow Cells; Bone marrow mesenchymal stem cells; Costunolide; Inter-promoted neuroprotection; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neuroprotection; Rats; Rats, Sprague-Dawley; Recellularization; Reproducibility of Results; Stroke
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.122823

[Display omitted] 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.