Human Stem Cells Used to Create Functional Liver Cells in Mice

Researchers have discovered a way to generate functional hepatocytes (liver cells) from human stem cells, which worked as expected and increased survival when transplanted into mice with acute liver injury, researchers reported in the July 9, 2013, advance online edition of Stem Cells and Development.

Over years or decades hepatitis B or C -- as well as other types of liver disease -- can lead to severe liver injury including cirrhosis and hepatocellular carcinoma, potentially leading to end-stage liver failure and the need for liver transplantation. Human donor livers are scarce, however, and researchers are exploring various alternative approaches.

Massoud Vosough from the Pasteur Institute of Iran describe a "bioreactor" they devised to make human pluripotent stem cells differentiate into functional hepatocyte-like cells.

After the cells were purified, they were transplanted into the spleens of mice with acute liver injury caused by a toxin. The transplanted cells performed multiple functions of normal hepatocytes including albumin secretion, collagen synthesis, glycogen storage, and cytochrome P450 activity. These cells engrafted successfully into the liver, and treated mice had increased survival compared with untreated mice.

Below is an edited except from a press release issued by journal publisher Mary Ann Liebert, Inc.discussing the research in more detail.

Human Stem Cell-derived Hepatocytes Regenerate Liver Function and Extend Survival in Mice with Hepatic Failure

New Rochelle, NY -- July 26, 2013 -- Researchers have generated functional hepatocytes from human stem cells, transplanted them into mice with acute liver injury, and shown the ability of these stem-cell derived human liver cells to function normally and increase survival of the treated animals. This promising advance in the development of cell-based therapies to treat liver failure resulting from injury or disease relied on the development of scalable, reproducible methods to produce stem cell-derived hepatocytes in bioreactors, as described in an article in Stem Cells and Development, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Stem Cells and Development website.

Massoud Vosough and coauthors demonstrate a large-scale, integrated manufacturing strategy for generating functional hepatocytes in a single suspension culture grown in a scalable stirred bioreactor. In the article "Generation of Functional Hepatocyte-Like Cells from Human Pluripotent Stem Cells in a Scalable Suspension Culture" the authors describe the method used for scale-up, differentiation of the pluripotent stem cells into liver cells, and characterization and purification of the hepatocytes based on their physiological properties and the expression of liver cell biomarkers.

David C. Hay, MRC Centre for Regenerative Medicine, University of Edinburgh, U.K., comments on the importance of Vosough et al.'s contribution to the scientific literature in his editorial in Stem Cells and Development entitled "Rapid and Scalable Human Stem Cell Differentiation: Now in 3D." The researchers "developed a system for mass manufacture of stem cell derived hepatocytes in numbers that would be useful for clinical application," creating possibilities for future "immune matched cell based therapies," says Hay. Such approaches could be used to correct mutated genes in stem cell populations prior to differentiation and transplantation, he adds.

"The elephant in the room for stem cell therapy rarely even acknowledged let alone addressed in the literature is that of scalable production of cells for translational application," says Editor-in-Chief Graham C. Parker, PhD, research professor, Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine. "Baharvand's groups' landmark publication not only demonstrates but exquisitely describes the methodology required to scale up stem cell populations for clinical application with a rigor to satisfy necessary manufacturing standards."

8/14/13

References

M Vosough, E Omidinia, M Kadivar, H Baharvand, et al. Generation of Functional Hepatocyte-Like Cells from Human Pluripotent Stem Cells in a Scalable Suspension Culture. Stem Cells and Development 22(20). July 9, 2013 (Epub ahead of print).

DC Hay. Rapid and Scalable Human Stem Cell Differentiation: Now in 3D. Stem Cells and Development 22(20). July 23, 2013 (Epub ahead of print).

Other Source

Mary Ann Liebert, Inc.Human stem cell-derived hepatocytes regenerate liver function and extend survival in mice with hepatic failure. Press release. July 26, 2013.