Preclinical Studies of Stem Cell Therapy for Heart Disease

Abstract

As part of the TACTICS (Transnational Alliance for Regenerative Therapies in Cardiovascular Syndromes) series to enhance regenerative medicine, here, we discuss the role of preclinical studies designed to advance stem cell therapies for cardiovascular disease. The quality of this research has improved over the past 10 to 15 years and overall indicates that cell therapy promotes cardiac repair. However, many issues remain, including inability to provide complete cardiac recovery. Recent studies question the need for intact cells suggesting that harnessing what the cells release is the solution. Our contribution describes important breakthroughs and current directions in a cell-based approach to alleviating cardiovascular disease.

Keywords: heart failure; infarction; regenerative medicine; stem cells.

Figure 1.. Procurement and isolation of MSCs

MSCs isolated from bone marrow and the mononuclear cells isolated by Ficoll density centrifugation. MSCs can be separated from other mononuclear cells by their plastic adherence in culture. From Williams and Hare

Figure 2.. Combination CSC/MSC.

Preload, afterload, and contractility changes after human cardiac stem cells (hCSC) and human mesenchymal stem cell (hMSCs). A. Left ventricular end-diastolic pressure (LVEDP) and (B) end-diastolic volume (EDV) and afterload measured by (C) arterial elastance (Ea). Combination hCSC/hMSC therapy improved contractility as measured by the (D) maximal rate of pressure change during systole (dP/dtmax) and (E) preload recruitable stroke work (PRSW), a preload-independent measure of stroke work. There was no change in (F) systolic elastance (Ees), in any of the groups. All graphs show pre-injection (2 weeks post-MI) vs 4-week post-injection values. Graphs represent mean±SEM. *P<0.05. From Williams et al..

Figure 3.. Different administration routes and cell types for treatment of heart disease.

The cell types listed under each delivery method refer only to those referenced (superscripted number) in this review. Figure adapted from Golpanian et al.