Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 688

Table 11.4. In the heart, transplantation of stem cells (including epicardial progenitor cells) is
aimed at repairing an infarcted myocardial region upon trilineage differentiation (cardiac and
smooth myocytes and endothelial cells) to recover the cardiac function, especially contractility,
and myocardial blood flow (Source: [ 1404 ]). Implanted stem cells can stimulate the recruit-
ment, survival, and differentiation of host stem cells. The former can liberate growth factors
(e.g., angiopoietin-1 and insulin-like [IGF1] and vascular endothelial [VEGF] growth factors),
chemokines (e.g., CXCL12), and antifibrotic mediators. Timing, delivery method (intravenous,
transarterial, as well as intracoronary, transvenous injection into coronary veins, and intramyocar-
dial, either epicardial or catheter-based transendocardial), and amount contribute to the clinical
outcome.

Cell differentiation Paracrine signaling

and migration

Tissue regeneration Protection against apoptosis

Adequate scar Homing of exogenous stem cells

Angiogenesis Migration of endogenous stem cells

Restitution of stem cell niches

therapy relies on long-term stem cell engraftment and survival as well as cooperation
between transplanted and host cells (Table 11.4 ). Performance of cell therapy indeed
relies on paracrine signaling launched by transplanted cells to support stem cell
homing, cell survival, angiogenesis, tissue development, and organ functioning.
Regeneration potential relies on tissue-resident stem cells. However, the number
of stem cells in tissues is less than 1 for 10 4 resident cells. Multiple stem cell
populations have been discovered in various organs in adults (e.g., blood, brain,
myocardium, skeletal muscle, and skin). In particular, hematopoietic stem cells
(HSC) can proliferate and differentiate to produce lymphoid and myeloid cell types.
Bone marrow-derived stem cells (bmSC) can differentiate into various unipotent
progenitors and then specialized cell types (e.g., cardiomyocytes).
Cells of certain tissues, such as skin, blood, and gut epithelia, have a great
turnover in normal conditions and are permanently replaced. These tissues can thus
be restored to their original state after injury. On the other hand, other tissues such
as the central nervous system can be repaired, but not completely restored.
Stem cells modulate tissue formation, maintenance, and repair. They most
often stay in relative quiescence, and reside in specialized microenvironments
(niches). Stem cells both: (1) self-renew and generate additional stem cells and
(2) differentiate into various progenitor cells. 9
Stem cell can thus be used in therapies that require repair, replacement, and
regeneration to stop and reverse damages caused by degenerative diseases or by

9 Transcription factors Nanog (for Tir Na Nog that means land of the ever young), octamer-
binding protein Oct4, and sex-determining region Y-box Sox2, coordinately contribute to stem cell
pluripotency and self-renewal of embryonic stem cells, activating genes that maintain pluripotency
and repressing those for differentiation. Moreover, Nanog, Oct4, and Sox2 have an autoregulatory
loop to allow rapid responses to environmental stimuli [ 1403 ].