Improvement of neural stem cell survival in collagen hydrogels by incorporating laminin-derived cell adhesive polypeptides.
Cell transplantation is a potential methodology for the treatment of Parkinson's disease. However, the therapeutic effect is limited by poor viability of transplanted cells. To overcome this problem, we hypothesized that a dual step approach, whereby providing an adhesive substrate for transplanted cells and, at the same time, by preventing the infiltration of activated microglia into the site of transplantation promotes the cell survival. To establish above conditions, attempts were made to prepare 3-D matrices using collagen hydrogels that incorporated integrin-binding polypeptides derived from laminin-1. Tandem combinations of laminin globular domains as well as a single globular domain 3 were prepared using recombinant DNA technology as a fusion with hexahistidine and bound to metal chelated surfaces to screen for the adhesion and proliferation of neural stem cells (NSCs). In addition, a small peptide derived from laminin γ1 chain was prepared and heterodimerized with the globular domain-containing chimeric proteins to evaluate for the enhancement of integrin-mediated cell adhesion. As a result, a heterodimer consisting of the globular domain 3 of the laminin α1 chain and the peptide from the laminin γ1 chain was selected as the best candidate among the polypeptides studied here for the incorporation into a collagen hydrogel. It was shown that the survival of NSCs was indeed promoted in the collagen hydrogel incorporating the heterodimer compared to the pure collagen hydrogel.
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Tadashi
T
Nakaji-Hirabayashi
Koichi
K
Kato
Hiroo
H
Iwata
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D007797:Laminin / Q000737:chemistry*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
D020100:Hydrogels; D007797:Laminin; D010455:Peptides; D003094:Collagen