Translating Stem Cell Research to Cardiac Disease Therapies

Abstract

Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of articles focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies. The first section by Rosen and Myerburg is an independent review that analyzes the basic science and translational strategies supporting the rapid advance of stem cell technology to the clinic, the philosophies behind them, trial designs, and means for going forward that may impact favorably on progress. The second and third sections were collected in response to the initial section of this review. The commentary by Francis and Cole discusses the Rosen and Myerburg review and details how trial outcomes can be affected by noise, poor trial design (particularly the absence of blinding), and normal human tendencies toward optimism and denial. The final, independent article by Marbán takes a different perspective concerning the potential for positive impact of stem cell research applied to heart disease and future prospects for its clinical application.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction

“…Despite the promise of MSC, linking preclinical CCT data in small animals with data in large animals and, eventually, humans has been an enormous challenge (8) In Vitro Bioluminescence Imaging of MSC-TF To determine levels of reporter gene activity, MSC-TF populations were assessed for FLUC2 activity. The following three populations were analyzed with bioluminescence imaging: (a) high-expressing MSC-TF from the first sort, (b) high-expressing MSC-TF from the second sort, and (c) highexpressing MSC-TF from the third sort.…”

“…Studies of CCT after treatment of mouse MI with MSC-TF indicated survival in the MI condition and significant differences in signal compared with MSC with no MI on day 14 (P = .016), and this trend was confirmed with ex vivo luciferase assays. Having achieved the required in clinical trials (8,28) have limited CCT implementation, in part due to the inability to link small-animal and large-animal preclinical data to clinical data. To address this, we designed a two-part study to use multimodality imaging as an enabling tool to analyze MSC for CCT and to achieve a specific small-animal imaging endpoint prior to the large-animal study.…”

Exploiting human iPS cell-derived cardiovascular cell populations toward cardiac regenerative therapy

“…pluripotent stem cells (PSCs), bone-marrow derived stem cells, skeletal myoblasts or cardiac stem cells] possessing cardiogenic potential have shaped the notion of stem cell-based cardiac restorative REVIEW therapy [7,8] . Despite much knowledge has been gained through numerous basic researches, clinical investigations in cardiac stem cell therapy using somatic stem cells with relatively small cohort still lack sufficient conclusive results to support full-scale implementation of the treatments [9,10] .…”

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

“…Stem cell-based therapies in small animal models have yielded promising but variable results [6][7][8]. Several studies have supported the use of large animals, such as pigs, with a similar heart size and physiology to humans, to monitor the survival, engraftment, and efficacy of transplanted hESC-derived cardiac cells [2][3][4][9][10][11][12]. However, the clinical application of cellbased therapies will require noninvasive imaging approaches that will allow in vivo monitoring of transplanted cells [7,8,13,14].…”