Universität zu Köln

Ziegler, Melanie ORCID: 0000-0002-6229-5698, Wang, Xiaowei ORCID: 0000-0001-8658-7399, 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 and Peter, Karlheinz (2017). Platelet-Targeted Delivery of Peripheral Blood Mononuclear Cells to the Ischemic Heart Restores Cardiac Function after Ischemia-Reperfusion Injury. Theranostics, 7 (13). S. 3192 - 3207. LAKE HAVEN: IVYSPRING INT PUBL. ISSN 1838-7640

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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-scFv(Sca-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-scFv(Sca-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-scFv(Sca-1+GPIIb/IIIa) is a promising candidate to enhance therapeutic cell delivery in order to promote myocardial regeneration and thereby preventing heart failure.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ziegler, Melanie UNSPECIFIED orcid.org/0000-0002-6229-5698 UNSPECIFIED Wang, Xiaowei UNSPECIFIED orcid.org/0000-0001-8658-7399 UNSPECIFIED Lim, Bock UNSPECIFIED UNSPECIFIED UNSPECIFIED Leitner, Ephraem UNSPECIFIED UNSPECIFIED UNSPECIFIED Klingberg, Franco UNSPECIFIED UNSPECIFIED UNSPECIFIED Ching, Victoria UNSPECIFIED UNSPECIFIED UNSPECIFIED Yao, Yu UNSPECIFIED UNSPECIFIED UNSPECIFIED Huang, Dexing UNSPECIFIED UNSPECIFIED UNSPECIFIED Gao, Xiao-Ming UNSPECIFIED UNSPECIFIED UNSPECIFIED Kiriazis, Helen UNSPECIFIED UNSPECIFIED UNSPECIFIED Du, Xiao-Jun UNSPECIFIED UNSPECIFIED UNSPECIFIED Haigh, Jody J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bobik, Alex UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagemeyer, Christoph E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ahrens, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED Peter, Karlheinz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-244017
DOI:	10.7150/thno.19698
Journal or Publication Title:	Theranostics
Volume:	7
Number:	13
Page Range:	S. 3192 - 3207
Date:	2017
Publisher:	IVYSPRING INT PUBL
Place of Publication:	LAKE HAVEN
ISSN:	1838-7640
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ACUTE MYOCARDIAL-INFARCTION; MESENCHYMAL STEM-CELL; BONE-MARROW-CELLS; PROGENITOR CELLS; ACTIVATED PLATELETS; INTRACORONARY INJECTION; VENTRICULAR-FUNCTION; SENSITIVE DETECTION; B-CELLS; REPAIR Multiple languages Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24401