Platelet-targeted delivery of peripheral blood mononuclear cells to the ischemic heart restores cardiac function after ischemia-reperfusion injury

Melanie Ziegler, Xiaowei Wang, Bock Lim, Ephraem Leitner, Franco Klingberg, Victoria Ching, Yu Yao, Dexing Huang, Xiao Ming Gao, Helen Kiriazis, Xiao Jun Du, Jody J. Haigh, Alex Bobik, Christoph E. Hagemeyer, Ingo Ahrens, Karlheinz Peter

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

One of the major hurdles in intravenous regenerative cell therapy is the low homing efficiency to the area where these cells are needed. To increase cell homing toward areas of myocardial damage, we developed a bispecific tandem single-chain antibody (Tand-scFvSca-1+GPIIb/IIIa) that binds with high affinity to activated platelets via the activated glycoprotein (GP)IIb/IIIa receptor, and to a subset of peripheral blood mononuclear cells (PBMC) which express the stem cell antigen-1 (Sca-1) receptor. Methods: The Tand-scFvSca-1+GPIIb/IIIa was engineered, characterized and tested in a mouse model of ischemia-reperfusion (IR) injury applying left coronary artery occlusion for 60 min. Fluorescence cell tracking, cell infiltration studies, echocardiographic and histological analyses were performed. Results: Treatment of mice undergoing myocardial infarction with targeted-PBMCs led to successful cell delivery to the ischemic-reperfused myocardium, followed by a significant decrease in infiltration of inflammatory cells. Homing of targeted-PBMCs as shown by fluorescence cell tracking ultimately decreased fibrosis, increased capillary density, and restored cardiac function 4 weeks after ischemia-reperfusion injury. Conclusion: Tand-scFvSca-1+GPIIb/IIIa is a promising candidate to enhance therapeutic cell delivery in order to promote myocardial regeneration and thereby preventing heart failure.

Original languageEnglish
Pages (from-to)3192-3206
Number of pages15
JournalTheranostics
Volume7
Issue number13
DOIs
Publication statusPublished - 2017

Keywords

  • Cell delivery
  • Cell tracking
  • Myocardial infarction
  • PBMC
  • Regenerative cell therapy
  • Single-chain antibody
  • Targeting

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