Cell surface engineering to enhance mesenchymal stem cell migration toward an SDF-1 gradient

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87 Scopus citations

Abstract

Mesenchymal stem cell (MSC) therapy for the treatment of myocardial infarction (MI) has shown considerable promise in clinical trials. A billion MSCs need to be administered for therapeutic efficacy, however, because only ~1% of the cells reach the ischemic myocardium after systemic infusion. This is due to the loss of the homing signal on the surface of the MSCs during their expansion in culture. Stromal-derived factor-1 (SDF-1) is up-regulated immediately after infarction and is released into the peripheral blood. This SDF-1 reaches the bone marrow and recruits CXC chemokine receptor 4 (CXCR4)-positive stem cells. The CXCR4/SDF-1 axis plays an important role in MSC homing to the ischemic myocardium. Since SDF-1 is highly expressed for only 48h after infarction, the current approaches requiring long-term culture of MSCs to induce CXCR4 expression are not clinically useful. To provide a clinically viable means to improve the homing of MSCs, we have developed a surface modification method to incorporate recombinant CXCR4 protein on the membrane of MSCs within 10min. Using this method, we have confirmed the improved migration of MSCs toward an SDF-1 gradient.

Original languageEnglish (US)
Pages (from-to)5627-5635
Number of pages9
JournalBiomaterials
Volume35
Issue number21
DOIs
StatePublished - Jul 2014
Externally publishedYes

Keywords

  • CXCR4
  • Mesenchymal stem cell
  • Myocardial infarction
  • SDF-1

ASJC Scopus subject areas

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

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