title: Combined transplantation of bone marrow stromal cell-derived neural progenitor cells with a collagen sponge and basic fibroblast growth factor releasing microspheres enhances recovery after cerebral ischemia in rats.
abstract: Bone marrow stromal cells (MSCs) are a useful source of cells because of their abundant supply and few associated ethical problems. We have previously reported that neural progenitor cells (NS-MSCs) can be effectively induced from MSCs and differentiate into neurons to contribute to functional recovery when transplanted into the rat stroke model. In this study, we attempted to enhance the therapeutic effects of NS-MSCs with a collagen sponge and basic fibroblast growth factor (bFGF) releasing microspheres. NS-MSCs were generated from MSCs by transfection of Notch-1 intracellular domain followed by culturing the cells in a free-floating culture system. The resulting NS-MSCs were transplanted into the rats with induced brain ischemia by using collagen sponges as scaffolds for transplanted cells, and with bFGF incorporated into gelatin microspheres to aid neovascularization around the transplanted region and proliferation of neural stem cells/neural progenitor cells. In culture, NS-MSCs successfully formed spheres containing cells highly expressing neural progenitor markers. Cell survival, neovascularization, and proliferation of host neural stem cells/neural progenitor cells were improved in animals that received NS-MSCs together with these biomaterials. Behavioral analysis also revealed significant functional recovery. These observations demonstrate that transplantation of NS-MSCs in combination with a collagen sponge and bFGF releasing microspheres significantly improves histological and functional recovery in the rat stroke model. When used with these biomaterials, NS-MSCs would be a promising cell source for treating stroke and neurodegenerative diseases.
authors: Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Dai
authors: D
authors: Matsuse
authors: Masaaki
authors: M
authors: Kitada
authors: Fumitaka
authors: F
authors: Ogura
authors: Shohei
authors: S
authors: Wakao
authors: Misaki
authors: M
authors: Kohama
authors: Jun-ichi
authors: J
authors: Kira
authors: Yasuhiko
authors: Y
authors: Tabata
authors: Mari
authors: M
authors: Dezawa
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D008863:Microspheres; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D016222:Fibroblast Growth Factor 2; D003094:Collagen