Tissue Engineering: Focus on the Cardiovascular System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 166

contractile cells, restoring function to the failing heart. Appropriate selection
of cells and biomaterials is the key factor in the construction of viable and
clinically relevant engineered tissue for myocardial regeneration. Various
stem cell types have been proposed for use in treatment of injured heart tis-
sue. However, the optimal cell type has yet to be established.
In this chapter, we will focus on derivation of human stem cells for use in
clinical applications of this nature. Implementation of human embryonic stem
cell and induced pluripotent stem cell (iPS)-based therapies will be discussed,
along with a review of the potential of adult stem cells, including bone marrow
cells (hematopoietic and mesenchymal stem cells), resident cardiac stem cells,
and skeletal muscle stem cells (satellite stem cells), in such clinical protocols.
The biomaterials used for creation of three-dimensional (3D) engineered tis-
sues dictate the scaffolding capacities necessary for organizing cells into appro-
priate tissue structures both in vitro and in vivo. The various applications of
biomaterials for such purposes will be discussed. Recent breakthroughs in tis-
sue engineering disciplines allowing for the design of biomaterial-based heart
tissue constructs have transformed this avenue into a promising approach
toward advancing myocardial repair. As the quality of engineered tissues con-
tinues to be optimized, vascularization of engineered tissues in efforts to aug-
ment construct viability, thickness, and architecture will also be introduced.
Human Cell Types for Cardiac Regeneration
Human Embryonic Stem Cells (hESCs)
The extensive proliferative and differentiative capacities of early embryonic
blastocyte-derived hESCs render them one of the most promising sources
of human cells for repair of injured tissue. Ever since successful isolation
of hESCs [1], which occurred twenty years after first reports of mouse ESC
(mESC) derivation [2, 3], extensive research efforts have been invested toward
inducing cardiomyocyte (CM) population propagation and purification from
hESC pools. The hESC in vitro-derived CMs (hES-CMs), first described by
Gepstein and colleagues [4] and later by others [5], have been extensively
characterized. Their unique early-stage cardiac potential features sarcomeric
structural patterning, spontaneous contractility, capacity to both structur-
ally and functionally integrate with preexisting cardiac tissue, responsive-
ness to pharmacological agents, and expression of cardiac-specific genes
[4-8]. Moreover, hES-CMs exhibit significant proliferative capacity both in
vitro (15-25% BrdU + cells) and in vivo, when compared with that of mESC-
CMs (<1% BrdU + cells) [9, 10]. Our works have shown that the number of pro-
liferating hES-CMs can be significantly augmented when cultured together
with endothelial and fibroblast cells on 3D polymeric scaffolds (Figure 8.1),
presumably via paracrine signaling [11]. Furthermore, upon transplantation