Growing liver from spleen

A team from Nanjing University and University of Macau has transformed the spleen to perform liver functions in mice, without transplanting cells or tissue from another body. The research is published online on 7 Jan in Gut, the official journal of the British Society of Gastroenterology.

At least two million people die each year due to liver diseases. For many patients, liver transplantation is their last hope, but the dearth of donor organs is a critical challenge worldwide. These researchers demonstrate that the abundant cells in another organ – the spleen – can take over the roles of the liver tissue, after a few steps of “transformation” (Figure 1). First, they injected silica particles to the mouse spleen, which stimulated the growth of a specific group of cells called fibroblasts. Then, they used gene vectors to overexpress three genes, namely Foxa3, Gata4 and Hnf1a, that convertedabout 2 × 10⁶ fibroblasts into hepatocytes (iHeps) in one spleen. Next, they increased the amount of three cytokines, namely TNF-α, EGF and HGF, which further expanded iHeps by four times (Figure 2). The spleen-transformed liver tissue exerted sufficient functions to save lives of the mice in which 90% of the liver was surgically removed (Figure 3).

For patients with end-stage liver diseases, their liver tissue is severely damaged. So, it is hard to restore the liver functions in the original site but expected to grow liver cells in another place (“ectopic regeneration”). But, where to grow a “new” liver is an unsolved question. There used to be voices of growing liver cells in lymph nodes, which is interesting but has little clinical significance. Because the liver is a large organ and has a huge number of cells required for performing even the most fundamental functions, anything offered in the size of a lymph nodes is less than a drop in the ocean. To address this challenge, for the first time, this team started their serial work by considering “transforming” an existing, large organ to perform the functions of the liver. One lead author of the paper, Professor Lei Dong of Nanjing University, is optimistic about the clinical translation of this technology. “Our method is direct, efficient, and different from all existing ones in that it does not involve cells or tissue from the outside,” he said, “so, it avoids many safety issues and immune injection. You can imagine that it directly works on the patient’s own cells.” The team have already started to test the technology in pigs and monkeys.  

Full-text link of the paper: https://gut.bmj.com/content/early/2022/01/06/gutjnl-2021-325018; Doi: 10.1136/gutjnl-2021-325018