Biomedical Engineering Reference
In-Depth Information
study, an incision was made through the liver parenchyma using a scissors. The in-
jury was 1 cm long and went completely through the liver, producing minimal cell
death but locally complete stromal disruption. The study showed that the adult liver
responded with inflammation and stellate cell activation, culminating in fibrosis
characterized by collagen deposition. By 7 days, and continuing through 28 days,
the area of injury was well demarcated as a linear scar with surrounding contrac-
tion of parenchymal and stromal tissues (Figs. 1.2-1.4). These findings showed
clearly that disruption of the extracellular matrix in the healthy mouse liver, both in
the adult and the neonate, did not lead to regeneration but rather to scar, similar to
other adult mammalian organs. This finding is in agreement with evidence follow-
ing resected lobes where it has been shown that these lobes never grow back (Goss
1992a, b; Michalopoulos and DeFrancis 1997). Thus, although it is well known that
liver restores its original mass and function following injury, we find no evidence
that liver injury of a local, stromal type regenerates.
Wound contraction in the healthy, acutely injured liver (both neonate and adult)
was measured following a cylindrical type of injury that was better suited to provide
the desired information on contraction (Ho et al. 2011). An example of measured
contraction in the injured liver of the adult mouse is reported in Chap. 4 (Fig. 4.4).
The question naturally arises whether the response of healthy liver to injury can
be used as a guideline for healing in the fibrotic liver. The chronic focal injuries
of liver fibrosis are different, in size and distribution as well as in the chronic in-
flammatory assault to the liver tissues, than those resulting from the acute injuries
described above. Of particular interest in this respect is the finding, observed in
several laboratories, that the most prevalent scar-forming cells in fibrotic liver are
contractile cells that stain for αSMA (so-called hepatic myofibroblasts; Forbes and
Parola 2011; Iwaisako et al. 2012; Kisseleva and Brenner 2012; Mallat and Loter-
sztajn 2013). These cells are the primary source of extracellular matrix in fibrosis
(excess collagen deposition) and are also involved in ECM remodeling and angio-
genesis.
This evidence does not prove that acute and chronic liver injuries heal identical-
ly; rather, it sets a suitable stage for further studies aimed at regeneration of healthy
tissue in fibrotic liver. As shown above, both in chronic and acute stromal injury in
the liver, the organ responded with a spontaneous wound healing response that is
characteristically similar to that observed with spontaneously healing skin wounds
and peripheral nerve wounds (Chap. 8). The appropriate collagen scaffold blocks
contraction in acutely injured sites in skin and peripheral nerves (Chaps. 8 and 9).
The liver studies described above encourage a study of chronic injury (fibrotic liv-
er) in which a collagen scaffold may conceivably be grafted on a surgically prepared
site in the diseased organ with the objective of regenerating a small but functionally
useful mass of liver tissue. Even a relatively small mass of functioning liver tissue
might delay over a long period the onset of terminal liver disease.
