Orientation-regulated immobilization of Jagged1 on glass substrates for ex vivo proliferation of a bone marrow cell population containing hematopoietic stem cells

Hiroyuki Toda, Masaya Yamamoto, Hiroshi Kohara, Yasuhiko Tabata

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Notch signaling has been recognized as a key pathway to regulate the proliferation and differentiation of hematopoietic stem cells (HSC). In this study, the orientation-regulated immobilization of a Notch ligand was designed to achieve the efficient Notch ligand-receptor recognition for the ex vivo proliferation of a bone marrow cell population containing HSC. Protein A was chemically conjugated onto aminated glass substrates, followed by immobilizing a recombinant chimeric protein of Jagged1 and Fc domain (Jagged1-Fc) through the biospecific binding between protein A and Fc domain. Protein A adsorption was suppressed for the Jagged1-Fc-immobilized substrates, in contrast to the Jagged1-Fc-coated ones, indicating the orientation-regulated immobilization of Jagged1-Fc for the substrates. Mouse lineage negative cells (Lin -) were cultured on the Jagged1-Fc-immobilized substrates. Flow cytometric analyses demonstrated that c-Kit +, Sca-1 +, Lin -, and CD34 - cells of an HSC population was significantly proliferated on the Jagged1-Fc-immobilized substrates 6 days after culture, whereas no proliferation was observed for the Jagged1-Fc-coated substrates in a random manner or Jagged1-Fc-immobilized ones with a Notch signaling inhibitor. It is concluded that the orientation-regulated immobilization of Jagged1-Fc increased the efficiency of Jagged1 to recognize the Notch receptors, resulting in the promoted ex vivo proliferation of the HSC population.

Original languageEnglish
Pages (from-to)6920-6928
Number of pages9
JournalBiomaterials
Volume32
Issue number29
DOIs
Publication statusPublished - 2011 Oct 1
Externally publishedYes

Keywords

  • Cell proliferation
  • Protein
  • Scaffold
  • Stem cell
  • Surface modification

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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