A Decellularized Liver Patch Improves Function in Rats
Decellularization involves stripping cells from donor tissue to leave behind the extracellular matrix and its chemical cues. That extracellular matrix can then be repopulated with patient-matched cells and transplanted, in principle minimizing many of the issues associated with tissue transplantation. The initial hype over decellularization has somewhat faded, but many groups continue to work with decellularized tissue in parallel with other approaches to tissue engineering. The production of thin patches of functional tissue to apply to organs such as the liver or heart has shown some promise in recent years, and here researchers demonstrate the ability to improve the function of damaged livers in rats via this strategy.
Liver fibrosis is primarily induced by liver inflammation, which triggers continuous secretion of the extracellular matrix (ECM) by hepatic stellate cells (HSCs). This secretion promotes liver repair, but eventually leads to fibrosis. The treatment of liver fibrosis is a complex process, and the optimal therapeutic strategy is to reverse the fibrotic progression. Conventional cell therapy has demonstrated promise in addressing fibrosis/cirrhosis. However, the direct infusion of hepatocytes faces challenges due to limited hepatocyte sources, poor cell viability, and the requirement for a large number of transplanted parenchymal functional hepatocytes.
Instead of stem cell therapy, liver tissue engineering presents another alternative therapeutic strategy. Tissue-engineering approaches for bioengineering of functional hepatic constructs shows potential to replicate liver physiological structures. However, to restore the normal hepatic architecture and functions, tissue engineering strategies for liver regeneration should position bioengineered hepatic constructs into the defect site of an injured liver instead of heterotopic implantation (subcutaneous or intraperitoneal accesses). Thus, cell sheet engineering technology holds promise because the transplanted cells might be better retained due to preserved contacts between the cells and the ECM.
We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin-complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin-DLM patches effectively mitigated CCl4-induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vivo, HGF/heparin-DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1 week, separately. Thus the newly designed hepatic patch holds promise for regeneration therapy and preventive health care for liver tissue engineering.