Japanese researchers report on liver transplantation studies using animal and iPS cells

Two research teams from the Okayama University Graduate School of Medicine (Okayama, Japan) have reported breakthrough studies in liver cell transplantation. One team found that the technical breakthrough in creating induced pluripotent stem cells (iPS) from mouse somatic cells (nonsex cells) in vitro had "implications for overcoming immunological rejection." Whereas a second team using liver cell xenotransplantation - transplanting cells of one species into another (in this case transplanting pig liver cells into mice) - found that transplanted liver cells from widely divergent species can function to correct acute liver failure and prolong survival.

Their studies, published in the current issue of Cell Transplantation (19:6/7), are freely available on-line at http://www.ingentaconnect.com/content/cog/ct/

Somatic cells differentiate into hepatocyte-like cells

A research team at the Okayama University Graduate School of Medicine, working with colleagues at the University of Pittsburgh School of Medicine found that mouse induced pluripotent stem (iPS) cells are pluripotent (able to differentiate into many varieties of stem cells) and able to proliferate in vitro without limits and could be cultured to become hepatocyte-like cells.

According to the researchers, a major limitation for cell-based therapies to treat liver diseases is the shortage of cell donors. Rejection is still an issue and chronic immunosuppression is required for allotransplantation (cells from nonidentical donors), making patient-derived cells, especially somatic cells (non-sex cells) attractive for transplantation.

"The ability to make iPS cells from somatic cells has implications for overcoming both immunological rejection and ethical issues associated with embryonic stem cells," said corresponding author Dr. Masaya Iwamuro. "Our study will be an important step in generating hepatocytes from human iPS cells as a new source for liver-targeted cell therapies."

The researchers found that the transplanted hepatocyte-like cells they produced from the mouse iPS cells increased the production of albumin and were also able to metabolize ammonia, which are characteristics of functional hepatocytes.

"In the future, studies will generate new therapies that include the transplantation of iPS cell-derived hepatocytes without immunological barrier, in vitro determination of toxicity, and the development of personalized health care by evaluating drugs for efficacy and toxicity on patient-specific hepatocytes," concluded Dr. Iwamuro.

Xenotransplantation for treating acute liver failure

In another related study, lead author Dr. Naoya Kobayashi, argued that a scarcity of human livers for transplantation and the greater supply of porcine liver cells (hepatocytes) suggest that once technical issues are overcome, porcine liver cells might be transplanted successfully into human livers. Their recent study successfully transplanted porcine hepatocytes into mice with acute liver failure.

"Using xenogenic hepatocytes from animals such as pigs might be advantageous for treating acute liver failure in humans," said Dr. Kobayashi. "Hepatocytes are the main active cells in the liver. However, removal from the liver causes hepatocytes major stress and potential loss of function. We tested a scaffold to improve the success of hepatocyte xenotransplantation."

According to Dr. Kobayashi, many scientists are making efforts to recreate a functional liver "outside its own niche," and their study involved creating a self-assembling peptide nanofiber (SAPNF) scaffold and testing its ability to function in vivo.

"In this xenotransplantation model, we found that the SAPNF has an excellent ability to promote hepatocyte engraftment and maintains tremendous hepatocyte functions capable of rescuing mice from acute liver failure," concluded Dr. Kobayashi, whose team worked with colleagues from the Baylor (Texas) University Institution for Immunology Research.

"These studies highlight the progress of Japanese research with respect to cell transplantation for liver disorders," said Dr. Paul Sanberg, coeditor-in-chief of the journal Cell Transplantation and director of the University of South Florida's Center of Excellence for Aging and Brain Repair.