Stem cell repair and liver cell activity.


Pilot trials of cirrhotic patients have demonstrated that the administration of autologous bone marrow cells into patients with liver failure induces clinical improvement. Mechanistically this may work through the process of transdifferentiation, that is, bone marrow directly differentiating to hepatocytes; alternatively, through indirect mechanisms such as production of cytokines.

A study was conducted (Zhou et al) in which human umbilical cord blood cells were administered into an animal model of liver failure.¹ This is made possible by specially bred mice whose immune systems can tolerate human stem cells. The investigators found that the cord blood cells incorporated into the damaged liver at a range of 3% to 14.2%. Most interestingly, the cells expressed several human hepatic markers such as liver-specific alpha1-antitrypsin messenger RNA, albumin and hepatocyte nuclear factor 1 protein. This was done without using any form of growth factor.

This result demands the continued investigation of cord blood and bone marrow cells for the treatment of liver failure. This has already been reported for CD34 positive cells, which have been used in clinical trials for liver failure and is now a focus for Regenecell using high dose cord blood mesenchymal and CD34+ cells with RegAmp™ for patients with liver disease.

Zhou et al suggest a more interesting and easier approach would be administration of the stem cell mobilizer G-CSF, which has been demonstrated to accelerate liver regeneration. This has been part of the Regenecell stem cell therapy program for the past two years.

In another study² Regenecell's protocol was again supported when the use of G-CSF in treatment of liver failure was investigated and the results proved:

1. Liver stem cells contained receptors for HGCSF
2. Injections of HGCSF promoted new cell production of liver stem cells.
3. HGCSF stimulated the bone marrow to contribute to liver repair.
4 The body produced its own HGCSF during the stimulated liver repair process.
5. The HGCSF stimulated the liver stem cells to divide and attracted more stem cells to contribute to the repair process.

We have advocated the use of RegAmp™ for all our procedures and are now seeing, as in the two studies mentioned here, more and more evidence pointing to the absolute necessity of using a growth factor like RegAmp™ in the treatment of patients with stem cells.

1. Zhou et al. Human progenitor cells with high aldehyde dehydrogenase activity efficiently engraft into damaged liver in a novel model. Hepatology 2009 Feb

2. Piscaglia et al. Granulocyte-colony stimulating factor promotes liver repair and induces oval cell migration and proliferation in rats. Gastroenterology. 2007 Aug;133(2):619-31)