FYI...Adult Stem Cells Take Root in Livers and Repair Damage

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http://www.sciencedaily.com/releases/2011/05/110511142134.htm

Adult Stem Cells Take Root in Livers and Repair Damage

ScienceDaily (May 22, 2011) — s Hopkins researchers have demonstrated that

human liver cells derived from adult cells coaxed into an embryonic state can

engraft and begin regenerating liver tissue in mice with chronic liver damage.

The work, published in the May 11 issue of the journal Science Translational

Medicine, suggests that liver cells derived from so-called " induced-pluripotent

stem cells (iPSCs) " could one day be used as an alternative to liver transplant

in patients with serious liver diseases, bypassing long waiting lists for organs

and concerns about immune system rejection of donated tissue.

" Our findings provide a foundation for producing functional liver cells for

patients who suffer liver diseases and are in need of transplantation, " says

Yoon-Young Jang, M.D., Ph.D., assistant professor of oncology at the s

Hopkins Kimmel Cancer Center. " iPSC-derived liver cells not only can be

generated in large amounts, but also can be tailored to each patient, preventing

immune-rejection problems associated with liver transplants from unmatched

donors or embryonic stem cells. "

iPSCs are made from adult cells that have been genetically reprogrammed to

revert to an embryonic stem cell-like state, with the ability to transform into

different cell types. Human iPSCs can be generated from various tissues,

including skin, blood and liver cells.

Although the liver can regenerate in the body, end-stage liver failure caused by

diseases like cirrhosis and cancers eventually destroy the liver's regenerative

ability, Jang says. Currently, the only option for those patients is to receive

a liver organ or liver cell transplant, a supply problem given the severe

shortage of donor liver tissue for transplantation. In addition, mature liver

cells and adult liver stem cells are difficult to isolate or grow in the

laboratory, she says. By contrast, iPSCs can be made from a tiny amount of many

kinds of tissue; and the embryonic stem-like iPSCs can grow in laboratory

cultures indefinitely.

For the study, Jang and colleagues generated human iPSCs from a variety of adult

human cells, including liver cells, fibroblasts (connective tissue cells), bone

marrow stem cells and skin cells. They found that though the iPSCs overall were

molecularly similar to each other and to embryonic stem cells, they retained a

distinct molecular " signature " inherited from the cell of origin.

Next, they chemically induced the iPSCs to differentiate first into immature and

then more mature liver cell types. Regardless of their origin, the different

iPSC lines all showed the same ability to develop into liver cells.

Using mice with humanlike liver cirrhosis, the researchers then injected the

animals with either 2 million human iPSC-derived liver cells or with normal

human liver cells. They discovered that the iPSC-derived liver cells engrafted

to the mouse liver with an efficiency of eight to 15 percent, a rate similar to

the engraftment rate for adult human liver cells at 11 percent.

Researchers also found the engrafted iPSCs worked well. The scientists detected

proteins normally secreted by adult human liver cells, including albumin,

alpha-1-antitrypsin, transferrin and fibrinogen, in the blood of mice

transplanted with human iPSC-derived liver cells.

Additional studies will need to be completed before clinical trials can begin,

Jang says. One concern has been the potential for embryonic stem cells or iPSCs

to cause tumors, though no tumors formed in any of the transplanted mice during

the seven months they were studied (equating to more than 30 years in a human

life). The scientists also plan to evaluate the impact of molecular memory that

may linger in iPSCs for other type of cellular fate changes.

Other scientists involved in the research were Hua Liu, Yonghak Kim, Saul

Sharkis and Luigi Marchionni from s Hopkins. The study was supported by the

National Institutes of Health and by the land Stem Cell Research Fund. Drs.

Jang and Sharkis have filed a patent for the development of iPSCs from human

hepatocytes.

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Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by s Hopkins Medical Institutions, via EurekAlert!,

a service of AAAS.

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Journal Reference:

1.H. Liu, Y. Kim, S. Sharkis, L. Marchionni, Y.-Y. Jang. In Vivo Liver

Regeneration Potential of Human Induced Pluripotent Stem Cells from Diverse

Origins. Science Translational Medicine, 2011; 3 (82): 82ra39 DOI:

10.1126/scitranslmed.3002376