Fibrin matrix provides a suitable scaffold for bone marrow stromal cells transplanted into injured spinal cord: a novel material for CNS tissue engineering.
Recent basic experiments have strongly suggested that cell transplantation therapy may promote functional recovery in patients with spinal cord injury (SCI). However, a safe and efficient transplantation technique still remains undetermined. This study, therefore, was aimed to clarify whether fibrin matrix could be a useful scaffold in bone marrow stromal cell (BMSC) transplantation for the injured spinal cord. To clarify the issue, three-dimensional structure of fibrin matrix was assessed and the green fluorescent protein (GFP)-expressing BMSC were cultured in fibrin matrix. The rats were subjected to spinal cord hemisection at T8 level, and the vehicle, BMSC or BMSC-fibrin matrix construct was implanted into the cavity. Neurologic function was serially evaluated. Using immunohistochemistry, we evaluated the survival, migration and differentiation of the transplanted cells at 4 weeks after transplantation. In the initial in vitro study, the BMSC could survive in fibrin matrix for 2 weeks. The animals treated with the BMSC-fibrin matrix construct showed significantly more pronounced recovery of neurologic function than vehicle- or BMSC-treated animals. Fibrin scaffold markedly improved the survival and migration of the transplanted cells. There was no significant difference in the percentage of cells doubly positive for GFP and microtubule-associated protein 2 between the animals treated with BMSC-fibrin matrix construct and those treated with BMSC, but a certain subpopulation of GFP-positive cells morphologically simulated the neurons in the animals treated with BMSC-fibrin matrix construct. These findings strongly suggest that fibrin matrix may be one of the promising candidates for a potential, minimally invasive scaffold for injured spinal cord, and that such strategy of tissue engineering could be a hopeful option in regeneration therapy for patients with SCI.
Itosaka
Hiroyuki
H
Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Kuroda
Satoshi
S
Shichinohe
Hideo
H
Yasuda
Hiroshi
H
Yano
Shunsuke
S
Kamei
Shintaro
S
Kawamura
Ryoichi
R
Hida
Kazutoshi
K
Iwasaki
Yoshinobu
Y
D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D002470:Cell Survival; D005337:Fibrin / Q000648:ultrastructure; D049452:Green Fluorescent Proteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000601:surgery* / Q000628:therapy*; D017154:Stromal Cells / Q000502:physiology / Q000637:transplantation*; D013904:Thoracic Vertebrae; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; D005337:Fibrin