Featured Research

from universities, journals, and other organizations

Macrophages, Not Stem Cells, Correct Liver Disease By Fusion

Date:
July 12, 2004
Source:
Oregon Health & Science University
Summary:
An Oregon Health & Science University study is defying a long-accepted assertion among many scientists that stem cells repair diseased tissue by transforming into other cell types in a process called plasticity.

PORTLAND, Ore. -- An Oregon Health & Science University study is defying a long-accepted assertion among many scientists that stem cells repair diseased tissue by transforming into other cell types in a process called plasticity.

The first study from OHSU's new Oregon Stem Cell Center, published in the current issue of the journal Nature Medicine, found that mature macrophages derived from bone marrow stem cells, and not bone marrow stem cells themselves, are what fuse with diseased liver cells, ultimately curing a genetic liver disease.

"The most important discovery is you don't need to transplant stem cells at all," said study co-author Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics, OHSU School of Medicine, and director of the Oregon Stem Cell Center. "If you transplant only macrophages, you'll get liver cells that correct liver disease in mice."

Holger Willenbring, M.D., postdoctoral fellow of molecular and medical genetics, and the study's lead author, called fusion between macrophages and hepatocytes, the cells in the liver that provide the typical functions of this organ, "a rare physiological, but potentially therapeutically exploitable, phenomenon."

"Macrophages are known to fuse with themselves," Holger said. "Therefore, it is not absolutely surprising that they can fuse with other cells as well, especially, since macrophages physiologically reside in the liver and comprise a substantial fraction of the liver cells.

Usually, they participate in resolving inflammation, taking care of debris and producing factors that help the liver to function. In addition, they provide a link between the bone marrow compartment and highly specified organ cells, and this is new and exciting because of therapeutic implications."

The findings are the latest in a series of discoveries by Grompe's laboratory since 2000, when it first showed blood-forming stem cells derived from bone marrow, called hematopoietic stem cells, can cure liver disease in mice. It later found that the liver cells were corrected by cell fusion rather than differentiation of the transplanted stem cells.

"Various labs have reported that bone marrow or blood stem cells are like super cells. They can turn into anything – liver, lung, brain, muscle," Grompe said. "Our thought was that blood stem cells are really there to repair all tissues, and we showed that you can cure liver disease with blood stem cell transplantation.

"Then we found out that the bone marrow cells were not turning into liver cells directly, but that they were fusing with preexisting liver cells instead. In cell fusion, two distinct cells meld to form a single, new cell. The liver cells were turning the blood cells into their own kind."

In the latest study, macrophages derived from bone marrow stem cells were transplanted into the spleens of mice with the genetic liver disease fumarylacetoacetate hydrolase deficiency, also called hereditary tyrosinemia in humans. Each mouse was injected with 1 million macrophages. The spleen, upstream from the liver, slowly releases the macrophages into the liver, which would otherwise wash cells away in its blood-rich environs. The result was "robust production" of functional hepatocytes..

"This means you can get away with using only macrophages in transplantation," Grompe said. "For bone marrow transplantation, to get a stem cell transplant to work, you need to treat the host with lethal doses of preparative irradiation, which has severe side effects. Here we show this harsh treatment is not necessary for macrophages to turn into useful liver cells."

Willenbring said transplantation of macrophages or their immediate, short-lived progenitors is much more targeted toward treatment of damaged liver tissue than using whole stem cells from which they're derived.

The discovery "strongly argues against stem cell plasticity because you're not using stem cells at all," Grompe said. To be sure, his laboratory used macrophages exclusively in the transplantation and "it worked." Macrophages also can more easily be grown in tissue culture than stem cells, and future studies will even look at whether they can be genetically modified before transplantation.

"That's the future. That's what we're trying to do," he said.

As for stem cell plasticity, Grompe said he and his colleagues "just don't see it," at least in liver cell repopulation.

"That could mean two things: We're blind, or it doesn't happen," he said. "I think the burden of proof is now on the people doing that work, to show that what they're seeing is not fusion."

The study was funded by the National Institutes of Health.


Story Source:

The above story is based on materials provided by Oregon Health & Science University. Note: Materials may be edited for content and length.


Cite This Page:

Oregon Health & Science University. "Macrophages, Not Stem Cells, Correct Liver Disease By Fusion." ScienceDaily. ScienceDaily, 12 July 2004. <www.sciencedaily.com/releases/2004/07/040708014035.htm>.
Oregon Health & Science University. (2004, July 12). Macrophages, Not Stem Cells, Correct Liver Disease By Fusion. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2004/07/040708014035.htm
Oregon Health & Science University. "Macrophages, Not Stem Cells, Correct Liver Disease By Fusion." ScienceDaily. www.sciencedaily.com/releases/2004/07/040708014035.htm (accessed September 20, 2014).

Share This



More Health & Medicine News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
How The 'Angelina Jolie Effect' Increased Cancer Screenings

How The 'Angelina Jolie Effect' Increased Cancer Screenings

Newsy (Sep. 19, 2014) Angelina's Jolie's decision to undergo a preventative mastectomy in 2013 inspired many women to seek early screenings for the disease. Video provided by Newsy
Powered by NewsLook.com
The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins