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Macroporous Dual-compartment Hydrogels for Minimally Invasive Transplantation of Primary Human Hepatocytes

Seale, Nailah, PhD1; Ramaswamy, Suvasini, PhD2; Shih, Yu-Ru, PhD3; Verma, Inder, PhD2; Varghese, Shyni, PhD1,3,4,5

doi: 10.1097/TP.0000000000002330
Original Basic Science—Liver

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.

Conclusions 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.

The authors investigate the therapeutic potential of a vascularizable dual compartment hydrogel system for primary hepatocytes subcutaneous implantation in a mouse model. It is demonstrated that such a cell transplant device can be used as a minimally invasive ectopic liver accessory for improving the function.

1 Department of Bioengineering, University of California, San Diego, La Jolla, CA.

2 Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA.

3 Department of Orthopaedic Surgery, Duke University, Durham, NC.

4 Department of Biomedical Engineering, Duke University, Durham, NC.

5 Department of Materials Science & Mechanical Engineering, Duke University, Durham, NC.

Received 4 April 2018. Revision received 3 May 2018.

Accepted 13 May 2018.

The authors declare no conflicts of interest.

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.

N.S. participated in research design, performance of the research, analysis, and writing of the article. S.R. conceived the idea, participated in research design, and editing the article. Y.-R.S. participated in animal surgeries and editing of the article. I.V. conceived the idea and edited the article. S.V. conceived the idea, participated in experimental design, data interpretation, and writing the article.

Correspondence: Shyni Varghese, PhD, Duke University, Room no. 381, 203 Research Dr., MSRB1 Durham, NC 27710. (shyni.varghese@duke.edu).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

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