title: Enhanced proliferation of neural stem cells in a collagen hydrogel incorporating engineered epidermal growth factor.
abstract: Neural stem cells (NSCs) have received much attention in cell-transplantation therapy for central nervous disorders such as Parkinson's disease. However, poor engraftment of transplanted cells limits the efficacy of the treatments. To overcome this problem, collagen-based hydrogels were designed in this study to provide microenvironments for embedded cells to survive and proliferate. Our approach was to incorporate epidermal growth factor (EGF), known as a mitogen for NSCs, into a collagen hydrogel. For the stable binding of EGF with collagen under mild conditions, EGF was fused with a collagen-binding polypeptide domain by recombinant DNA technology. A cell population containing NSCs was derived from the fetal rat brain and cultured in the composite hydrogels for 7 d followed by analysis for cell proliferation. It was shown that the number of living cells was significantly higher in hydrogels incorporating collagen-binding EGF. This effect is largely owing to the collagen-binding domain that serves to sustain presentation of EGF toward cells within the hydrogel. It is further revealed by gene expression analysis that cells proliferated in the EGF-incorporating collagen hydrogel contained subpopulations expressing the marker of stem cells, neurons, astrocytes, or oligodendrocytes.
authors.affiliation: Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Edgar Y
authors.initials: EY
authors.lastname: Egawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Makiko
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakaji-Hirabayashi
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D020100:Hydrogels / Q000737:chemistry*; D008422:Materials Testing; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D020100:Hydrogels; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D003094:Collagen