Prof. Tsvee Lapidot and Dr. Orit Kollet of the Weizmann Institute's Immunology Department have found how the liver, when damaged, sends a cry for help to these stem cells. "When the liver becomes damaged, it signals to stem cells in the bone marrow, which rush to it and help in its repair – as liver cells," says Lapidot. His research team has found that certain molecules that govern normal development of the liver become overproduced when it is damaged, signaling to the stem cells in the bone marrow to come to the site. The scientists were able to pinpoint the signaling molecules – HGF, MMP-9 and SDF-1– and describe the homing process. HGF is involved in liver cell development and, in irregular cases, can play a role in cancer metastasis. MMP-9 assists cell migration from the blood system into various types of tissue, including liver tissue. SDF-1 is a molecule that stem cells are attracted to. The scientists discovered that large amounts of HGF and MMP-9, when overproduced in the damaged liver, enter the blood flow and increase the sensitivity of stem cells in the bone marrow to SDF-1. Suddenly able to sense SDF-1's calling signal from the liver (which itself is amplified due to increased production and distribution of SDF-1), the stem cells migrate from the bone marrow into the blood and navigate their way to the liver. The findings could lead to new insights into organ repair and transplants, especially liver-related ones. They may also uncover a whole new stock of stem cells that can under certain conditions become liver cells. Until a few years ago only embryonic stem cells were thought to possess such capabilities. Understanding how stem cells in the bone marrow turn into liver cells could one day be a great boon to liver repair as well as an alternative to the use of embryonic stem cells.
Prof. Tsvee Lapidot's research is supported by the Concern Foundation, Beverly Hills, CA; Ms. Rhoda Goldstein, Nanuet, NY; Levine Institute of Applied Science; M.D. Moross Institute for Cancer Research; Ms. Nora Peisner, Hungtington, MI; and Gabrielle Rich Center for Transplantation Biology Research.