Abstract

Introduction: Fabrication of three-dimensional (3D) liver tissue is limited by many factors, one of them is the lack of vascularization in the tissue-engineered constructs. To overcome these limitations, an in vivo engineered liver pocket-scaffold's ability to increase neo-angiogenesis was considered in the present study. Methods: Hyaluronan-besed scaffolds enriched with human Mesenchymal Stem Cells (hMSCs) and hepatocytes were implanted into rats. Angiogenesis and hepatocyte function were monitored. Results: The formation of de novo vascular networks within scaffolding matrices was noted as well as a better albumin production by the implanted hepatocytes. Conclusions: Our results emphasized that the presence in culture of hMSC increased tissue concentrations of growth factors and may promote angiogenesis resulting in a higher density of blood vessels coupled with a better metabolic support of hepatocytes.

Highlights

  • Liver transplantation still represents the only effective treatment for patients with liver failure

  • A hyaluronan (HA)-based scaffold enriched with human Mesenchymal Stem Cells and rat hepatocytes was preconditioned in a bioreactor system, implanted into the liver of rats

  • HYAFF-11TM, a derivative of hyaluronic acid, was used as scaffold. This scaffold has previously found many applications in the biomedical field due to its low antigenicity, suitable biodegradability, and good mechanical and hemostatic properties [17]. This HA-based scaffold presents a great similarity with the structure of native extracellular matrix (ECM) and is almost completely biodegradable ensuring the formation of neo-tissue with collagen and elastic fibers completely organized [18,19,20]

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Summary

Introduction

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]. A suitable perfusion of metabolically active tissue requires intimate localization of cells to a dense vasculature in a highly organized manner [10,11] In light of these considerations, we have considered recent advances in the field of stem cell and nanotechnology research in order to produce a vascularized and functional tissue-engineered liver graft [12,13,14,15,16]. A hyaluronan (HA)-based scaffold was used as biodegradable platform to study the behavior of human Mesenchymal Stem Cells (hMSCs) in co-culture with hepatocytes

Results and Discussion
Biomaterial
Animals
Hepatocytes isolation from Rat Liver
MTT assay
Albumin ELISA assay
Real-time PCR
3.10. Statistical analysis
Conclusions
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