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

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

Cite this

Ziegler, Melanie ; Wang, Xiaowei ; Lim, Bock ; Leitner, Ephraem ; Klingberg, Franco ; Ching, Victoria ; Yao, Yu ; Huang, Dexing ; Gao, Xiao Ming ; Kiriazis, Helen ; Du, Xiao Jun ; Haigh, Jody J. ; Bobik, Alex ; Hagemeyer, Christoph E. ; Ahrens, Ingo ; Peter, Karlheinz. / Platelet-targeted delivery of peripheral blood mononuclear cells to the ischemic heart restores cardiac function after ischemia-reperfusion injury. In: Theranostics. 2017 ; Vol. 7, No. 13. pp. 3192-3206.
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title = "Platelet-targeted delivery of peripheral blood mononuclear cells to the ischemic heart restores cardiac function after ischemia-reperfusion injury",
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.",
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author = "Melanie Ziegler and Xiaowei Wang and Bock Lim and Ephraem Leitner and Franco Klingberg and Victoria Ching and Yu Yao and Dexing Huang and Gao, {Xiao Ming} and Helen Kiriazis and Du, {Xiao Jun} and Haigh, {Jody J.} and Alex Bobik and Hagemeyer, {Christoph E.} and Ingo Ahrens and Karlheinz Peter",
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Platelet-targeted delivery of peripheral blood mononuclear cells to the ischemic heart restores cardiac function after ischemia-reperfusion injury. / Ziegler, Melanie; Wang, Xiaowei; Lim, Bock; Leitner, Ephraem; Klingberg, Franco; Ching, Victoria; Yao, Yu; Huang, Dexing; Gao, Xiao Ming; Kiriazis, Helen; Du, Xiao Jun; Haigh, Jody J.; Bobik, Alex; Hagemeyer, Christoph E.; Ahrens, Ingo; Peter, Karlheinz.

In: Theranostics, Vol. 7, No. 13, 2017, p. 3192-3206.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Platelet-targeted delivery of peripheral blood mononuclear cells to the ischemic heart restores cardiac function after ischemia-reperfusion injury

AU - Ziegler, Melanie

AU - Wang, Xiaowei

AU - Lim, Bock

AU - Leitner, Ephraem

AU - Klingberg, Franco

AU - Ching, Victoria

AU - Yao, Yu

AU - Huang, Dexing

AU - Gao, Xiao Ming

AU - Kiriazis, Helen

AU - Du, Xiao Jun

AU - Haigh, Jody J.

AU - Bobik, Alex

AU - Hagemeyer, Christoph E.

AU - Ahrens, Ingo

AU - Peter, Karlheinz

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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