Re: Stem Cells reverse liver failure in mice

[Guest guest]

Thanks for sharing this . It sounds exciting.Now is definitely the time to raise funds for research.We need to get all our people off the transplant list.I am interested in what Dave and our other scientists think.LeeHello Everyone,A member of my local PSC support group is a medical researcher and he keeps up on liver research. The following is an excerpt of an email he sent me. It's kind of hard to understand but hopefully and you other scientists and doctors in the group can understand it. The "Chris" he refers to is Bowlus, hepatologist and PSC researcher. We haven't heard back from yet. Mouse research is a long way from human treatment but this does give hope:This Fall, Harvard researchers halted liver failure by injectingmice with a medium that contained bone marrow-derived stem cells. They alsoinjected labeled immune cells (lymphocytes) into the mice and could see themleave the liver after the treatment. This seems to be a shift in the typeof immune response (from TH1 to TH2). I sent the papers a couple ofmonths ago. I believe that this is the first time that liver failure has been stopped.Plus it is a very different use of biological therapy (cytokine therapy). Iam really excited about this discovery. The damage to the liver appears tobe mediated by these destructive immune cells (cytotoxic T lymphocytes andnatural killer cells). The destructive process is a chain with many links.We only need to stop one link in the chain and we can slow or stop the liverdamage -- even reverse it. I am extremely positive about this finding. Itpromises to be a new way to use stem cells for therapy, and I see no reasonwhy it should not slow, stop or even reverse liver damage in PSC patients. One key cytokine secreted by the stem cells is IL-10 (Interleukin 10). Thiscytokine is known as one of the main factors that changes the immuneresponse from TH1 to TH2. TH1 is the response that results in destroyingcells. We know of over 200 cytokines. These are little protein signals thatcontrol immune responses. The problem is that, with so many differentcytokines, it would take a long time to figure out what combination to useto have a certain effect, such as the effect here: calling off the dogs thatattack the liver. The beautiful thing is that the stem cells just happen toput out the right combination of cytokine signals. To me, it seems thatthey show up in the liver to rebuild it, so when they get there they call ofthe demolition crew. (Sacramento dx UC and PSC 2001)

[Guest guest]

Hi ;

I just want to make sure that we are on the same page. Are you referring to these two papers from the Yarmush group at Harvard?

PLoS ONE 2: e941 (2007) Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. Parekkadan B, van Poll D, Suganuma K, EA, Berthiaume F, Tilles AW, Yarmush ML. PMID: 17895982

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1978513 & blobtype=pdf

Biochem. Biophys. Res. Commun. 363: 247-252 (2007) Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. Parekkadan B, van Poll D, Megeed Z, Kobayashi N, Tilles AW, Berthiaume F, Yarmush ML. PMID: 17869217

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2096777 & blobtype=pdf

Best regards,

Dave R.

[Guest guest]

Hi ;

Having read the two papers by the Yarmush group from Harvard (see my message #98790), I can certainly see some promising findings here, but I honestly don't know how relevant their animal (rat) model of liver failure is to human PSC. As I understand it, they inject the rats with a liver toxin, D-galactosamine. Some molecules (possibly cytokines) excreted by bone-marrow-derived mesenchymal stem cells seem to delay/inhibit liver failure, and these factors may include interleukin-10 and tumor necrosis factor-alpha. It seems odd to me that tumor necrosis factor-alpha is implicated as one of the 'protective' cytokines here, since one of the goals of IBD therapy these days seems to be to block tumor necrosis factor-alpha with molecules like Remicade (infliximab; an anti-tumor necrosis factor antibody). I guess I am not quite as enthusiastic as your medical researcher, and would like to see further research results.

Best regards, and Happy New year to all PSCers and their caregivers.

Dave

(father of (22); PSC 07/03; UC 08/03)

>> Hello Everyone,> > A member of my local PSC support group is a medical researcher and he keeps up on liver research. The following is an excerpt of an email he sent me. It's kind of hard to understand but hopefully and you other scientists and doctors in the group can understand it. The "Chris" he refers to is Bowlus, hepatologist and PSC researcher. We haven't heard back from yet. Mouse research is a long way from human treatment but this does give hope:> > This Fall, Harvard researchers halted liver failure by injecting> mice with a medium that contained bone marrow-derived stem cells. They also> injected labeled immune cells (lymphocytes) into the mice and could see them> leave the liver after the treatment. This seems to be a shift in the type> of immune response (from TH1 to TH2). I sent the papers a couple of> months ago. > > I believe that this is the first time that liver failure has been stopped.> Plus it is a very different use of biological therapy (cytokine therapy). I> am really excited about this discovery. The damage to the liver appears to> be mediated by these destructive immune cells (cytotoxic T lymphocytes and> natural killer cells). The destructive process is a chain with many links.> We only need to stop one link in the chain and we can slow or stop the liver> damage -- even reverse it. I am extremely positive about this finding. It> promises to be a new way to use stem cells for therapy, and I see no reason> why it should not slow, stop or even reverse liver damage in PSC patients. > > One key cytokine secreted by the stem cells is IL-10 (Interleukin 10). This> cytokine is known as one of the main factors that changes the immune> response from TH1 to TH2. TH1 is the response that results in destroying> cells. > > We know of over 200 cytokines. These are little protein signals that> control immune responses. The problem is that, with so many different> cytokines, it would take a long time to figure out what combination to use> to have a certain effect, such as the effect here: calling off the dogs that> attack the liver. The beautiful thing is that the stem cells just happen to> put out the right combination of cytokine signals. To me, it seems that> they show up in the liver to rebuild it, so when they get there they call of> the demolition crew.> > (Sacramento dx UC and PSC 2001)>