Biomedical Engineering Reference
In-Depth Information
Integrins are receptors that help mediate the connection between the cell and the
surrounding matrix. One way in which mechanotransduction is thought to take place
is through integrins, which are regarded as mechanosensors due to the conforma-
tional changes they adopt when affected by external forces. Two integrins that have
been found to exhibit this behavior are the a5b1 and the aLb2 integrins [
75
]. When
the apical surface of an endothelial cell experiences shear stress due to the blood flow
acting on it, the tension experienced by the cell is transferred to integrins. These
integrins, now activated, increase adhesion to the ECM, which alters the phenotype
of the cell. In order to maximize adhesion, the cell needs to increase the surface area
in contact with the ECM so it flattens in a fashion consistent with the blood flow. This
allows the side of the cell facing the oncoming blood flow to resist more tension,
while the opposite end of the cell will experience less tension [
35
]. This would
increase the endothelial cell's chance of survival when under the influence of high
rates of blood flow and the consequent shear stress.
Human liver can regenerate its original functional mass after hepatectomy and
stops this process once the structure of the organ is rebuilt and its normal size
restored. The developmental signaling mechanism that serves as the basis for this
phenomena requires understanding in order to apply similar regenerative capacity
in other organs. Identifying inductive factors that guide stem cells to differentiate
into various cell types within different organs can be used as part of a therapeutic
strategy.
Interestingly, we have recently shown that after unilateral pneumonectomy
(PNX), activation of capillary endothelial cells plays a critical role in initiating and
sustaining the regeneration of the lung, another organ constantly subjected to both
cell cyclic stretch and changing blood flow [
76
]. It is plausible that the altered
blood flow inside pulmonary vasculature post PNX ignites the activation of
VEGFR2, which in turn stimulates the expansion of epithelial progenitor cells. In
addition, it is tempting to postulate that changing pulmonary mechanics also plays
an essential role in activating epithelial progenitor cells inside alveoli.
Induction of (organ-specific) stem cell differentiation alone may not be suffi-
cient to complete the regeneration process, and creation of the proper local
environmental cues and architectural arrangements inherent to the dynamic in vivo
setting has been shown to play an integral role. To this end, the physical inter-
actions between cells, ECM, and blood flow, as well as the molecular cross-talk
between these constituents play a significant role in tissue regeneration. For
example, transplanting hepatocytes in patients with end-stage liver disease results
in suboptimal outcomes. With the identified inductive function of LSECs in both
initiating and supporting hepatocyte amplification, co-transplantation of properly
primed LSECs or pre-conditioning of the host's vasculature would significantly
enhance hepatocyte reconstitution, as well as facilitate the engraftment of injected
functional hepatocytes via optimized cellular interactions.
The self-regenerative capacity of the liver is frequently hampered by detri-
mental factors such as extensive resection, hepatotoxins, aging, and tumor
metastasis. Thus, end-stage liver disease often requires transplantation therapy.
However,
lack
of
available
liver
tissue
consistently
curbs
successful
liver
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