Molecular Imaging of Bone Marrow Mononuclear Cell Homing and Engraftment in Ischemic Myocardium

¹ Department of Cardiothoracic Surgery, Stanford
² Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Medicine, Division of Cardiology. Stanford University School of Medicine, Stanford, CA, USA.
⁵ Molecular Imaging Program at Stanford (MIPS); Department of Medicine, Division of Cardiology. Stanford University School of Medicine, Stanford, CA, USA.

^* To whom correspondence should be addressed. E-mail: joewu{at}stanford.edu.

	Abstract

Bone marrow mononuclear cell (BMMC) therapy shows promise as a treatment for ischemic heart disease. However, the ability to monitor long-term cell fate remains limited. We hypothesize molecular imaging can be used to track stem cell homing and survival after myocardial ischemia-reperfusion (I/R) injury. We first harvested donor BMMCs from adult male L2G85 transgenic mice constitutively expressing both firefly luciferase (Fluc) and enhanced green fluorescence protein (eGFP) reporter gene. FACS analysis revealed 0.07% of the population to consist of classical hematopoietic stem cells (lin-, thy-int, c-kit+, Sca-1+). Afterwards, adult female FVB recipients (n=38) were randomized to sham surgery or acute I/R injury. Animals in the sham (n=16) and I/R (n=22) groups received 5x10⁶ of the L2G85-derived BMMCs via tail vein injection. Bioluminescence imaging (BLI) was used to track cell migration and survival in vivo for 4 weeks. BLI showed preferential homing of BMMCs to hearts with I/R injury compared to sham hearts within the first week following cell injection. Ex vivo analysis of explanted hearts by histology confirmed BLI imaging results, and quantitative RT-PCR (for the male Sry gene) further demonstrated higher number of BMMCs in hearts with I/R injury compared to the sham group. Functional evaluation by echocardiography demonstrated a trend towards improved left ventricular fractional shortening in animals receiving BMMCs. Taken together, these data demonstrate that molecular imaging can be used to successfully track BMMC therapy in murine models of heart disease. Specifically, we demonstrate that systemically delivered BMMCs preferentially home to and are retained by injured myocardium.

This article has been cited by other articles:

				J. C. Wu Molecular Imaging: Antidote to Cardiac Stem Cell Controversy J. Am. Coll. Cardiol., November 11, 2008; 52(20): 1661 - 1664. [Full Text] [PDF]

				P. Leucht, J.-B. Kim, R. Amasha, A. W. James, S. Girod, and J. A. Helms Embryonic origin and Hox status determine progenitor cell fate during adult bone regeneration Development, September 1, 2008; 135(17): 2845 - 2854. [Abstract] [Full Text] [PDF]

				S. J. Zhang and J. C. Wu Comparison of Imaging Techniques for Tracking Cardiac Stem Cell Therapy J. Nucl. Med., December 1, 2007; 48(12): 1916 - 1919. [Full Text] [PDF]