Multifunctional chimeric proteins for the sequential regulation of neural stem cell differentiation

Bioconjugate Chemistry
Tadashi Nakaji-HirabayashiHiroo Iwata

Abstract

Controlling the dynamics of growth factor signaling is a challenge in regenerative medicine for various tissues including the central nervous system. Here, we report on the development of the biomolecular system that facilitates sequential regulation of growth factor signals acting on neural stem/progenitor cells. Recombinant technology was employed to synthesize the multifunctional chimeric protein that contained multiple domains, including epidermal growth factor (EGF), ciliary neurotrophic factor (CNTF), globular capping domain, thrombin-cleavable sequence, and substrate-binding domain with affinity for Ni(II) ions. The chimeric protein is expected to expose CNTF upon elimination of the capping domain by digestion with endogenous thrombin in vivo. When the multifunctional chimeric protein was immobilized onto a substrate through the coordination of the substrate-binding domain with surface-immobilized Ni(II) ions, the substrate served to proliferate neural stem cells, maintaining the population of undifferentiated cells at 85%. This effect is primarily due to the activity of EGF, while CNTF activity is temporally veiled with the capping domain. Upon digesting the thrombin-cleavable sequence to remove the capping domain, the ...Continue Reading

References

May 18, 2000·Nature Neuroscience·A Björklund, O Lindvall
Aug 1, 2000·Colloids and Surfaces. B, Biointerfaces·I HirataY Ikada
Oct 31, 2000·Microscopy Research and Technique·B L Patton
Nov 4, 2000·Trends in Biotechnology·K J KallenS Rose-John
May 1, 2001·Nature Biotechnology·M A CaldwellC N Svendsen
Jun 6, 2003·Progress in Neurobiology·Volkmar LessmannMarzia Malcangio
Dec 31, 2003·Molecular and Cellular Neurosciences·John A BoockvarDonald M O'Rourke
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hidenori YokoiShuguang Zhang
Jul 27, 2005·Langmuir : the ACS Journal of Surfaces and Colloids·Koichi KatoHiroo Iwata
Apr 22, 2006·Journal of Alzheimer's Disease : JAD·Paula GrammasLakshmi Thirumangalakudi
May 5, 2006·Seminars in Thrombosis and Hemostasis·Wolfram Bode
Jun 17, 2006·Biochemical and Biophysical Research Communications·Da Yong LeeByung Kwan Jin
Jul 5, 2006·The European Journal of Neuroscience·Piercesare Grimaldi, Ferdinando Rossi
Nov 23, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yoon Seong KimTong H Joh

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Citations

Aug 30, 2008·Current Opinion in Biotechnology·Shara M DellatoreWilliam M Miller
Jan 28, 2017·Colloids and Surfaces. B, Biointerfaces·Miku NishidaKazuyoshi Matsuoka
Oct 7, 2016·Journal of Materials Chemistry. B, Materials for Biology and Medicine·T Nakaji-HirabayashiK Ishihara
Dec 28, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·T Nakaji-Hirabayashi, H Kitano

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