Abstract
The construction of a three-dimensional (3D) liver tissue is limited by many factors; one of them is the lack of vascularization inside the tissue-engineered construct. An engineered liver pocket-scaffold able to increase neo-angiogenesis in vivo could be a solution to overcome these limitations. In this work, a hyaluronan (HA)-based scaffold enriched with human mesenchymal stem cells (hMSCs) and rat hepatocytes was pre-conditioned in a bioreactor system, then implanted into the liver of rats. Angiogenesis and hepatocyte metabolic functions were monitored. The formation of a de novo vascular network within the HA-based scaffold, as well as an improvement in albumin production by the implanted hepatocytes, were detected. The presence of hMSCs in the HA-scaffold increased the concentration of growth factors promoting angiogenesis inside the graft. This event ensured a high blood vessel density, coupled with a support to metabolic functions of hepatocytes. All together, these results highlight the important role played by stem cells in liver tissue-engineered engraftment.
Highlights
Liver transplantation still represents the only effective treatment for patients with liver failure
A hyaluronan (HA)-based scaffold was used as biodegradable platform to study the behavior of human mesenchymal stem cells co-cultured with hepatooccyytteess
The morphological analyses demonstrated that in pocket-scaffolds consisting of rat hepatocytes and human mesenchymal stem cells (hMSCs) the formation of new vessels occurred in the edge of the scaffold; a significant migration of neo-developed vessels extended centripetally from the border towards the center of the matrix
Summary
Liver transplantation still represents the only effective treatment for patients with liver failure. In order to deal with this problem, many researchers have attempted to develop different extracorporeal bioartificial liver systems to provide a temporary support for exhausted liver; these are cell-based life support devices intended to enhance hepatic detoxification and protein synthesis functions in order to compensate for a whole liver [2,3,4,5]. Such supports are limited and can only temporarily replace a subset of essential hepatic functions, suggesting the necessity to recapitulate all liver function by alternative approaches. A hyaluronan (HA)-based scaffold was used as biodegradable platform to study the behavior of human mesenchymal stem cells (hMSCs) co-cultured with hepatooccyytteess
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