Assessment of Electromechanically Stimulated Bone Marrow Stem Cells
Seeded Acellular Cardiac Patch in a Rat Myocardial Infarct Model
Abstract
Although substantial progress has been made in tissue engineered cardiac
patch, the translation of such strategies into a clinical setting has
always face setbacks due to the lack of appropriate scaffolds and cell
resources. Here, we evaluated cardiomyogenic differentiation of
electromechanically stimulated rat bone marrow-derived stem cell
(rt-BMSCs) on an acellular bovine pericardium (aBP) as well as the
performance of this engineered patch in a rat myocardial infarct (MI)
model. Briefly, aBP was prepared using a detergent-based
decellularization procedure. The formed aBPs were seeded with rt-BMSCs
and then stimulated under electrical, mechanical or electromechanical
conditions (3-millisecond pulses of 5 V/cm at 1 Hz, 5% streching) to
enhance cardiomyogenic differentiation. Thereafter, electromechanically
stimulated patch was applied on MI region over a time period (3 weeks).
After this period, the retrieved patch and infarct region were evaluated
in terms of calcification, inflammatory reaction (CD68), cell migration
from patch to host tissue and sarcomere structure related protein
expressions. Patch related calcification was not examined in all tested
group. Moreover, higher number of BrdU-labelled cells and low level of
CD68 positive cells were observed in the infract region under
electromechanically stimulated conditions as compared with static
conditions. More importantly, MHC, SAC, Troponin T and N-cad positive
cells were observed in both infarct region and retrieved engineered
patch after the 3 weeks. As a result, we showed that a noticeable
differentiation of stem cells on an acellular patch into cardiomyocytes
under the electromechanical stimulation. This patch successfully
integrated with the host tissue via cell migration from the patch to the
infarct region.