Macroporous dual compartment hydrogels for minimally invasive transplantation of primary human hepatocytes

Background Given the shortage of available organs for whole or partial liver transplantation, hepatocyte cell transplantation has long been considered a potential strategy to treat patients suffering from various liver diseases. Some of the earliest approaches that attempted to deliver hepatocytes via portal vein or spleen achieved little success due to poor engraftment. More recent efforts include transplantation of cell sheets or thin hepatocyte laden synthetic hydrogels. However, these implants must remain sufficiently thin to ensure that nutrients can diffuse into the implant. Methods To circumvent these limitations, we investigated the use of a vascularizable dual compartment hydrogel system for minimally invasive transplantation of primary hepatocytes. The dual compartment system features a macroporous outer Polyethylene glycol diacrylate/ Hyaluronic acid Methacrylate hydrogel compartment for seeding supportive cells and facilitating host cell infiltration and vascularization, and a hollow inner core to house the primary human hepatocytes. Results We show that the subcutaneous implantation of these cell-loaded devices in NOD/SCID mice facilitated vascular formation while supporting viability of the transplanted cells. Furthermore, the presence of human serum albumin in peripheral blood and the immunostaining of excised implants indicated that the hepatocytes maintained function in vivo for at least 1 month, the longest assayed time point. Conclusion Cell transplantation devices that assist the anastomosis of grafts with the host can be potentially used as a minimally invasive ectopic liver accessory to augment liver specific functions as well as potentially treat various pathologies associated with compromised functions of liver such as hemophilia B or alpha-1 antitrypsin deficiency. Corresponding author. Address: Duke University, 203 Research Dr., MSRB1 Room No. 381, Durham, NC 27710 USA, Email address: shyni.varghese@duke.edu, Phone: +1-919-66- 5273, Fax: +1-919-681-8490 Authorship Nailah Seale: Participated in research design, performance of the research, analysis and writing of the manuscript Suvasini Ramaswamy: Conceived the idea, participated in research design, and editing the manuscript Yu-Ru Shih: Participated in animal surgeries and editing of the manuscript. Inder Verma: Conceived the idea and editing the manuscript Shyni Varghese: Conceived the idea, participated in experimental design, data interpretation, and writing the manuscript. Disclosures None. Funding S.V and I.V acknowledges the generous financial support from California Institute of Regenerative Medicine grants (RT3-07907 and TR4-06809). N.M.S. Acknowledges the funding support of the National Science Foundation Graduate Research Fellowship Program. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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