Challenges in the translation of cardiovascular cell therapy

Abstract

Ischemic cardiovascular diseases cause a significant burden of morbidity and mortality throughout the world. Over the past decade, we have learned a tremendous amount about the biology of various stem and progenitor cells. Multiple preclinical experiments have demonstrated significant bioactivity in a wide variety of stem and progenitor cells. Early clinical trials have also shown some promising results. This review will focus on the current challenges in the translation of cell therapy to a viable clinical therapy. Additionally, we will highlight the role of cardiovascular imaging and molecular imaging in the future of stem cell therapy.

FIGURE 1

Use of bioluminescence imaging to track injected bone marrow mononuclear cells (BMNCs) in vivo. BMNCs were obtained from β-actin-luc mice, which ubiquitously express firefly luciferase gene under control of constitutive β-actin promoter. Either BMNCs alone or BMNCs with specific biomatrix designed to enhance cell fate were transcutaneously injected into limb muscle. Cell fate was serially and non-invasively tracked by measurement of luminescence emission in response to systemic luciferin injection. Serial imaging demonstrates prolonged presence of BMNCs after local application with addition of biomatrix. (Courtesy of Joern Tongers, Feinberg Cardiovascular Research Institute, Northwestern University, and Department of Cardiology, Hannover University Medical School.)

FIGURE 2

Differences between PET of relative and absolute coronary perfusion after adenosine infusion. (A) Stress imaging of relative perfusion for patients 1 and 2 demonstrates similar perfusion defects. Both have decreased perfusion in mid and basal inferior walls. (B) Coronary flow reserve based on absolute flow in mL/min/g demonstrates 2 different patterns. Patient 1 has focal defect in inferior wall, whereas patient 2 has global hypoperfusion consistent with physiology of triple-vessel coronary artery disease. Coronary angiography demonstrated occluded RCA in patient 1 and occluded RCA with severe, diffuse CAD in patient 2. ANT = anterior; AV = atrioventricular node; D = diagonal; INF = inferior; LAD = left anterior descending; LAT = lateral; LCx = left circumflex; OM = obtuse marginal; RCA-PDA = right coronary artery-posterior descending artery; RI = ramus intermedius; SEP = septal. (Reprinted with permission of (51).)