Tissue Development, Repair, and Remodeling - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 695

increases synthesis of extracellular matrix constituents much more than in the
absence of dynamical loading.
Smooth myocytes cultured in a three-dimensional collagen-1 matrix, stimulated
by PDGF and TGF

and cyclic mechanical loading respond accordingly to the
combination of chemical and mechanical stimuli [ 1428 ]. The produced effects
depend on the nature of the extracellular matrix.
In vitro investigations on cultured cells can simplify the reality because impor-
tant, more or less unknown, factors can be neglected, in particular blood supply.
Signaling associated with local and regional needs as well as the state of the whole
organism is neglected.
By analogy with ecology, histological niches better define the cell status, living
site, functioning, and interactions with the environment. Bioreactors must then
replicate the niche. For example, endothelial cells constitute a niche component of
adult neural stem cells. 22 Osteoblasts lining the inner bone surface are associated
with hematopoietic stem cells. 23
A scaffold made of natural and synthetic materials that acts as a temporary
extracellular matrix, with a nourishing supply bathed with growth factors is seeded
by cells that thrive and adapt to produce engineered tissue to be implanted in
the body. Synthetic biomaterials are thus developed for use as three-dimensional
extracellular environments that mimic the regulatory characteristics of natural
extracellular matrix and ECM-bound growth factors. Support biomaterials include
self-assembling fibrillar networks and other protein polymers that present bioac-
tive ligands and respond to cell signals. Such cues can lead to remodeling and
developmental processes involved in tissue-specific differentiation with suitable
structure-function relationships. Besides, bone marrow cultured in growth matrix
can be used to yield angiogenesis. Moreover, mesoscale tissular modules can be
assembled and associated with vascular supplies to form vascularized engineered
tissues with significant viable cell densities [ 1431 ].
Tissue production depends on interactions between the growing tissue and its
environment. The dynamic environment within bioreactors, in particular stimulation
by mechanical stresses under control to avoid cell damage significantly affect tissue
growth and development.

β

22 In the hippocampus, adult neural stem cells receive cues not only from astrocytes [ 1429 ], but
also from endothelial cells [ 1430 ]. Endothelial cells, but not vascular smooth myocytes, release
factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance
neuron production, activating the Notch pathway. The signaling between adult stem and support
cells involves the same molecular pathways as during embryogenesis, such as the Notch, TGF β ,

BMP, and Wnt axes.
23 Osteoblasts have plasmalemmal Jagged-1 ligand that activates Notch receptor of hematopoietic
stem cells. Stimulated Notch pathway leads to hematopoietic stem cell self-renewal.