Transplantation of 3D MSC/HUVEC spheroids with neuroprotective and proangiogenic potentials ameliorates ischemic stroke brain injury
| Autor: | Yu-Jie Lin, Bing-Huan Wu, Yu-Chun Lin, Jui-Che Chuang, Yu-Jen Lu, Ting-Wei Hsu, Chieh-Cheng Huang, Li-Chi Chen, Yu-Ting Huang, Hsin-Wen Wang, Li-Hung Hsieh, Yi-Qiao Fang |
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| Rok vydání: | 2021 |
| Předmět: |
Biophysics
Bioengineering 02 engineering and technology Mesenchymal Stem Cell Transplantation Regenerative medicine Neuroprotection Brain Ischemia Biomaterials Cell therapy Mice 03 medical and health sciences Paracrine signalling Spheroids Cellular Animals Medicine Ischemic Stroke 030304 developmental biology 0303 health sciences business.industry Regeneration (biology) Mesenchymal stem cell Endothelial Cells 021001 nanoscience & nanotechnology Stroke Transplantation Mechanics of Materials Brain Injuries Ceramics and Composites Cancer research Stem cell 0210 nano-technology business |
| Zdroj: | Biomaterials. 272:120765 |
| ISSN: | 0142-9612 |
| Popis: | Ischemic stroke, and the consequent brain cell death, is a common cause of death and disability worldwide. Current treatments that primarily aim to relieve symptoms are relatively inefficient in achieving brain tissue regeneration and functional recovery, and thus novel therapeutic options are urgently needed. Although cell-based therapies have shown promise for treating the infarcted brain, a recurring challenge is the inadequate retention and engraftment of transplanted cells at the target tissue, thereby limiting the ultimate therapeutic efficacy. Here, we show that transplantation of preassembled three-dimensional (3D) spheroids of mesenchymal stem cells (MSCs) and vascular endothelial cells (ECs) results in significantly improved cell retention and survival compared with conventional mixed-cell suspensions. The transplanted 3D spheroids exhibit notable neuroprotective, proneurogenic, proangiogenic and anti-scarring potential as evidenced by clear extracellular matrix structure formation and paracrine factor expression and secretion; this ultimately results in increased structural and motor function recovery in the brain of an ischemic stroke mouse model. Therefore, transplantation of MSCs and ECs using the 3D cell spheroid configuration not only reduces cell loss during cell harvesting/administration but also enhances the resultant therapeutic benefit, thus providing important proof-of-concept for future clinical translation. |
| Databáze: | OpenAIRE |
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