Tissue Engineering: Focus on the Cardiovascular System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 176

to synchronously and spontaneously beat when partly overlaid one over
another [111]. A keynote paper published by Miyahara and colleagues [67]
described the construction of a cell sheet from adipose tissue-derived MSCs.
After transplantation into the infarcted rat heart, the cell sheet gradually
evolved to form a thick, vascularized graft, which contained CMs and undif-
ferentiated MSCs and stimulated improved heart functioning.
decellularized Matrix
Tissue-engineered constructs can also be generated from decellularized
cadaveric tissue to then serve as the basis for engineering whole tissue
organs or segmental patches. Following treatment with detergents, only
ECM and vascular network components remain, which can then be re-
seeded with functional cells and cultured under physiological conditions.
This approach takes advantage of natural blood supply networks, intended
to enhance graft viability. Proof of concept studies have been performed by
Ott and colleagues [113], who demonstrated feasibility of rat heart decellu-
larization while preserving its natural chambers, valves, and vasculature.
The acellular heart construct, re-seeded with CMs or endothelial cells and
sustained in a bioreactor that provided pulsatile flow and pacing, reached
~34% recellularization and exhibited pumping function equivalent to ~2% of
adult rat heart potential within 8 days in culture.
Tissue constructs formed of decellularized matrices embedded with stem
cells have been evaluated by Tan et al. [114] in the context of heart repair.
Decellularized small intestinal submucosa (SIS) embedded with MSCs and
cultivated in vitro for 5-7 days was then transplanted into an infarcted rabbit
heart and monitored for one month. Heart function was more significantly
upgraded following engraftment SIS-MSC grafts, compared to acellular SIS.
Moreover, MSCs migrated toward the infarcted area, where they differenti-
ated into CMs and smooth muscle cells.
Singelyn et al. have proposed combination of decellularized and injectable
biomaterial matrices for formulation of a myocardial matrix more closely
mimicking the natural tissue [115]. They decellularized porcine myocardial
tissue, which was then processed to form a viscous myocardial matrix gel-
able at 37 o C. Intense neovascularization was detected within the graft area,
following its injection into the rat myocardium, with a significant increase
in the number of mature blood vessels at 11 days post-transplantation.
Similarly, Wei et al . combined the decellularization and cell sheet engi-
neering approaches [116] to generate thick cardiac patches. MSC cell sheets
inserted between slices of acellular bovine pericardium scaffold layers were
transplanted four weeks after infraction in rats, underwent integration, and
became enriched with neo-vessels and neo-muscles, where blood vessel den-
sity increased four-fold, compared to the untreated infarct group. In addi-
tion, a small fraction of transplanted MSCs expressed mature CM markers.