Dynamic Imaging of Allogeneic Mesenchymal Stem Cells Trafficking to Myocardial Infarction

Abstract

Background— Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated. Methods and Results— With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI. Conclusions— Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.

Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation

“…When injected into fetal sheep, individual MSCs show site-specific differentiation [5]. In non-human adult primates, engraftment is lower, but both autologous and allogeneic MSCs can be detected in a wide range of organs [5][6][7]. However, a large proportion of MSCs are trapped either in the lung during first passage after intravenous infusion or in the microvasculature when infused on the arterial side [8,9].…”

Over-expression of CXCR4 on mesenchymal stem cells augments myoangiogenesis in the infarcted myocardium

“…Mesenchymal stem cells (MSCs) have a potential to regenerate cardiac myocytes following acute myocardial infarction (MI) [1]. However, mobilized cells into infarcted tissue are subject to cell death due to insufficient oxygen [2].…”

Experimental study of bone marrow-derived mesenchymal stem cells combined with hepatocyte growth factor transplantation via noninfarct-relative artery in acute myocardial infarction

“…MI is, by nature, an irreversible injury. 6,7 After an MI, some heart cells are lost and others hibernate because they are underperfused. Cell transplantation and gene therapy offer the promise to replace the lost cells (myogenesis) and to perfuse the hibernating cells (angiogenesis).…”