Timing of bone marrow cell delivery has minimal effects on cell viability and cardiac recovery after myocardial infarction

Rutger Jan Swijnenburg, Johannes A. Govaert, Koen E.A. Van Der Bogt, Jeremy I. Pearl, Mei Huang, William Stein, Grant Hoyt, Hannes Vogel, Christopher H. Contag, Robert C. Robbins, Joseph C. Wu

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Background-Despite ongoing clinical trials, the optimal time for delivery of bone marrow mononuclear cells (BMCs) after myocardial infarction is unclear. We compared the viability and effects of transplanted BMCs on cardiac function in the acute and subacute inflammatory phases of myocardial infarction. Methods and Results-The time course of acute inflammatory cell infiltration was quantified by FACS analysis of enzymatically digested hearts of FVB mice (n=12) after left anterior descending artery ligation. Mac-1 +Gr-1 high neutrophil infiltration peaked at day 4. BMCs were harvested from transgenic FVB mice expressing firefly luciferase (Fluc) and green fluorescent protein (GFP). Afterward, 2.5 ×10 6 BMCs were injected into the left ventricle of wild-type FVB mice either immediately (acute BMC) or 7 days (subacute BMC) after myocardial infarction, or after a sham procedure (n=8 per group). In vivo bioluminescence imaging showed an early signal increase in both BMC groups at day 7, followed by a nonsignificant trend (P=0.203) toward improved BMC survival in the subacute BMC group that persisted until the bioluminescence imaging signal reached background levels after 42 days. Compared with controls (myocardial infarction+saline injection), echocardiography showed a significant preservation of fractional shortening at 4 weeks (acute BMC versus saline; P<0.01) and 6 weeks (both BMC groups versus saline; P<0.05) but no significant differences between the 2 BMC groups. FACS analysis of BMC-injected hearts at day 7 revealed that GFP + BMCs expressed hematopoietic (CD45, Mac-1, Gr-1), minimal progenitor (Sca-1, c-kit), and no endothelial (CD133, Flk-1) or cardiac (Trop-T) cell markers. Conclusion-Timing of BMC delivery has minimal effects on intramyocardial retention and preservation of cardiac function. In general, there is poor long-term engraftment and BMCs tend to adopt inflammatory cell phenotypes.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalCirculation: Cardiovascular Imaging
Volume3
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • Bioluminescent imaging
  • Bone marrow mononuclear cells
  • Delivery timing
  • Myocardial infarction

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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