Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 692

Bone marrow-derived mesenchymal stem cells that overexpress the Pkb1 gene
(that encode PKB1 kinase) are better for cell therapy of acute myocardial infarction.
Secretion of paracrine cytoprotective factors from stem cells exerts an effect on
cardiomyocytes exposed to hypoxia [ 1421 ].
A mixed ester of hyaluronan with butyric and retinoic acid acts as a cardio-
and vasculogenic agent in human mesenchymal stem cells isolated particularly
from fetal membranes of term placenta. Hyaluronan with butyric and retinoic acids
primes stem cell differentiation into endothelial and cardiac cells [ 1422 ].

11.4.1.6 Embryonic Stem Cells

Embryonic stem cells differentiate into all cell types, especially cardiomyocytes
organized in myofibers when stimulated by suitable cardiac promoters, but they can
produce teratomas. Moreover, they can form ectopic pacemakers.
Human embryonic stem cells can differentiate to cardiomyocytes using activin-
A and BMP4 factors. However, a mixed cell population with cardiomyocytes,
endothelial cells, and fibroblasts must be cultured in a rotating orbital shaker to
create human, functional, prevascularized, cardiac tissue patches [ 1423 ]. Preformed
microvessels can anastomose with the host coronary circulation.
In summary, transdifferentiation has stimulated multiple clinical trials. Cardiac
progenitors from the cardiac population and cardiomyogenic cells derived from
adult bone marrow stromal cells are able to differentiate into cardiomyocytes when
interacting with cardiomyocytes. Regenerative cardiology trials most often use
bone marrow cells and mesenchymal stem cells, because cardiac stem cells do not
generate significant repair. However, the results of stem cell injection in hearts after
heart attack at most show slight, transient benefit. Cell treatment optimization hence
remains challenging, taking into account disease type, patient history, associated
therapy for the selection of the cell type, associated growth factors, delivery route,
and administration timing.

11.4.2 Gene Therapy

Genes encode transcripts for the synthesis of proteins required for cell structures and
functions. Gene therapy is the delivery of genetic materials into cells using viral and
non-viral gene carriers, or vectors. Gene transfer technology is aimed at correcting
defective genes responsible for lesions and thus repairing diseased tissues. Normal
genes are inserted within the genome to replace abnormal genes.