In vivo functional and transcriptional profiling of bone marrow stem cells after transplantation into ischemic myocardium

Ahmad Y. Sheikh, Bruno C. Huber, Kazim H. Narsinh, Joshua M. Spin, Koen Van Der Bogt, Patricia E. De Almeida, Katherine J. Ransohoff, Daniel L. Kraft, Giovanni Fajardo, Diego Ardigo, Julia Ransohoff, Daniel Bernstein, Michael P. Fischbein, Robert C. Robbins, Joseph C. Wu

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Objective-: Clinical trials of bone marrow-derived stem cell therapy for the heart have yielded variable results. The basic mechanism(s) that underlies their potential efficacy remains unknown. In the present study, we evaluated the survival kinetics, transcriptional response, and functional outcome of intramyocardial bone marrow mononuclear cell (BMMC) transplantation for cardiac repair in a murine myocardial infarction model. Methods and Results-: We used bioluminescence imaging and high-throughput transcriptional profiling to evaluate the in vivo survival kinetics and gene expression changes of transplanted BMMCs after their engraftment into ischemic myocardium. Our results demonstrate short-lived survival of cells following transplant, with less than 1% of cells surviving by 6 weeks posttransplantation. Moreover, transcriptomic analysis of BMMCs revealed nonspecific upregulation of various cell regulatory genes, with a marked downregulation of cell differentiation and maturation pathways. BMMC therapy caused limited improvement of heart function as assessed by echocardiography, invasive hemodynamics, and positron emission tomography. Histological evaluation of cell fate further confirmed findings of the in vivo cell tracking and transcriptomic analysis. Conclusion-: Collectively, these data suggest that BMMC therapy, in its present iteration, may be less efficacious than once thought. Additional refinement of existing cell delivery protocols should be considered to induce better therapeutic efficacy.

Original languageEnglish (US)
Pages (from-to)92-102
Number of pages11
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • angiogenesis
  • cell physiology
  • imaging agents
  • ischemic heart disease
  • vascular biology

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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