Pretargeting and Bioorthogonal Click Chemistry-Mediated Endogenous Stem Cell Homing for Heart Repair

ACS Nano. 2018 Dec 26;12(12):12193-12200. doi: 10.1021/acsnano.8b05892. Epub 2018 Dec 4.

Abstract

Stem cell therapy is one of the promising strategies for the treatment of ischemic heart disease. However, the clinical application of stem cells transplantation is limited by low cell engraftment in the infarcted myocardium. Taking advantage of pretargeting and bioorthogonal chemistry, we engineered a pretargeting and bioorthogonal chemistry (PTBC) system to capture endogenous circulating stem cells and target them to the injured heart for effective repair. Two bioorthogonal antibodies were i.v. administrated with a pretargeting interval (48 h). Through bioorthogonal click reaction, the two antibodies are linked in vivo, engaging endogenous stem cells with circulating platelets. As a result, the platelets redirect the stem cells to the injured heart. In vitro and in vivo studies demonstrated that bioorthogonal click reaction was able to induce the conjugation of platelets and endothelial progenitor cells (EPCs) and enhance the binding of EPCs to collagen and injured blood vessels. More importantly, in a mouse model of acute myocardial infarction, the in vivo results of cardiac function, heart morphometry, and immunohistochemistry assessment all confirmed effective heart repair by the PTBC system.

Keywords: bioorthogonal click chemistry; endogenous stem cells; engineered antibodies; heart repair; pretargeting.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / metabolism
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Cells, Cultured
  • Click Chemistry*
  • Collagen / chemistry
  • Collagen / metabolism
  • Disease Models, Animal
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / metabolism
  • Heart Diseases / metabolism
  • Heart Diseases / therapy*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Antibodies
  • Collagen