Self-assembling chimeric protein for the construction of biodegradable hydrogels capable of interaction with integrins expressed on neural stem/progenitor cells.
The poor survival of neural stem/progenitor cells following transplantation into the brain is the major problem limiting the effect of cell-based therapy for Parkinson's disease. To overcome this problem, we are involved in designing keratin-based hydrogels that serve as physical barriers to prevent the infiltration of inflammatory cells. Another feature of the hydrogels is to contain a polypeptide that promotes integrin-mediated cell adhesion. To construct such hydrogels, a chimeric protein consisting of an alpha-helical polypeptide and a globular domain derived from laminin was synthesized by means of recombinant DNA technology and coassembled with extracted keratins that form hydrogels through intermolecular coiled-coil association of alpha-helical segments. It was found that neurosphere-forming cells specifically adhered to the keratin-based composite hydrogel and actively proliferated at a high survival rate. These results suggested that the composite hydrogel provides microenvironments suitable for the survival and proliferation of neural progenitor cells.
Nakaji-Hirabayashi
Tadashi
T
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Kato
Koichi
K
Iwata
Hiroo
H
D002448:Cell Adhesion; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002470:Cell Survival; D020100:Hydrogels / Q000737:chemistry*; D016023:Integrins / Q000096:biosynthesis / Q000378:metabolism*; D007633:Keratins; D009474:Neurons / Q000737:chemistry / Q000166:cytology*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*
D020100:Hydrogels; D016023:Integrins; D011993:Recombinant Fusion Proteins; D007633:Keratins