期刊
BIOMATERIALS
卷 109, 期 -, 页码 1-11出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.09.007
关键词
Spheroid; Cell transplantation; Non-viral gene transfection; Spinal cord injury; Biodegradable polycation
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [25000006, 24300170, 15H03017, 15k20962]
- Center of Innovation Program (COI) from MEXT
- Japan Society for the Promotion of Science (JSPS)
- JSPS Core-to-Core Program
- A. Advanced Research Networks
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [15K20962, 15H03017] Funding Source: KAKEN
Curing spinal cord injury (SCI) is challenging because of the onset of multiple and irreversible pathological responses to such injury. To suppress the responses, we employed an advanced cell transplantation technology integrating three-dimensional spheroid cell transplantation with non-viral gene transfection using biodegradable polycations. Brain-derived neurotrophic factor (BDNF)-transfected mesenchymal stem cell (MSC) spheroids were transplanted at thoraces level (Th9) to SCI region in mice. BDNF-transfected MSC spheroid transplantation led to a significantly enhanced recovery of hindlimb motor function in acute phase of SCI with myelinated axons preserved at the SCI region, while use of either technology in isolation, BDNF transfection or spheroid culture, exerted only a limited therapeutic effect, demonstrating the importance of integrated approaches. Secretion of endogenous therapeutic proteins, such as anti-inflammatory factors, was greater in MSC spheroids than in monolayer culture MSCs, and these factors appeared to act synergistically alongside BDNF secretion in SCI treatment. This study forms a basis for cell therapy regulating complex pathophysiologic processes. (C) 2016 Elsevier Ltd. All rights reserved.
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