<no subject>

[Guest guest]

OK, DUMB QUESTION, WHY ISN'T anybody doing anything with stem-cells and

Nf2?

Custom-Tailored Cellular Therapies for Genetic Ills

Source: Whitehead Institute for Biomedical Research

03/11/2002

While the promise of nuclear transplantation therapy, commonly referred to

as " therapeutic cloning, " has given hope to patients such as

Reeve and excited the research community and the public, it has never been

successfully demonstrated.

Now, scientists from the Whitehead Institute for Biomedical Research have

used a mouse model to establish for the first time that a combination of

nuclear transplantation, gene therapy and embryonic stem cell

differentiation can be used to create custom-tailored cellular therapies for

genetic disorders.

The work is a result of a collaboration between Whitehead Member Rudolf

Jaenisch's lab and Whitehead Fellow Daley's lab and have been

published as two companion papers on the website of the journal Cell on

Friday, March 8, 2002.

The Whitehead researchers joined forces to work on a problem that until now

has proven difficult to overcome. Scientists have been able to use nuclear

transfer to create embryonic stem cells and differentiate them in culture to

create many different cell types, including muscle, neurons, and

hematopoietic stem cells, which are the precursors to all immune and blood

cells.

But they have never shown that the cells created in culture could be

reintroduced into an animal to treat a disease.

Combining their independent research interests, the Jaenisch and Daley labs

used skin cells from a mouse that was completely immune deficient to create

a cellular therapy that was able to partially restore immune function in the

mouse.

" Though the immune system wasn't completely restored, there was enough

improvement to predict that a comparable result in humans would translate

into a significant clinical benefit, " says Daley.

" This is a proof-of-principle experiment which shows that nuclear

transplantation therapy may be possible for human application. Furthermore,

it shows that gene therapy can be incorporated into the approach to correct

genetic mutations in defective cells without affecting the germ line, " added

Jaenisch.

Postdoctoral fellow Rideout and graduate student Konrad

Hochedlinger, both of the Jaenisch lab, used the nuclear transfer procedure

to remove the nucleus, which contains the DNA of a cell, from an egg and

replace it with the nucleus from a skin cell of an adult mouse with a

genetic immune deficiency.

In this procedure, the egg resets the developmental clock of the adult

nucleus and the reprogrammed cell starts developing into an embryo that is

genetically identical to the donor cell.

At the stage when the embryo develops into a hollow ball of approximately a

hundred cells, called a blastocyst, it contains a nub composed of embryonic

stem (ES) cells that have the potential to become any cell in the body.

The ES cells from the blastocyst were isolated and the genetic defect

causing the immune deficiency was corrected by gene therapy.

These corrected embryonic stem cells, however, couldn't be successfully

transplanted into the adult mouse to treat the immune disorder. For some

reason, adult mice reject transplants of blood cell precursors derived from

embryonic stem cells in culture.

" While embryonic stem cells could be induced to form hematopoietic cells in

culture, these cells wouldn't reliably generate the blood and immune system

when transplanted into mice. For the last 15 years, engrafting mice with

blood derived from embryonic stem cells has been the Holy Grail of the

field, " explained Daley.

Kyba, a postdoctoral fellow in the Daley lab, found a way to achieve

this goal by inserting a gene called HoxB4 that stimulates blood cell

proliferation. The HoxB4 modified cells generated hematopoietic stem cell

precursors that could be successfully transplanted into adult mice.

With this newfound ability, the researchers applied the same strategy to the

genetically corrected embryonic stem cells made from the immunodeficient

mouse. Remarkably, these genetically corrected cells were able to partially

rescue the immune systems of mice suffering from complete immune deficiency.

In principle, this approach might be useful some day for treating human

patients with immune deficiency ( " bubble boy disease " ) or be applied to a

host of other genetic diseases that can be corrected by cell

transplantation. Embryonic stem cells can form any tissue in the body,

including neurons, muscle cells of the heart, and pancreatic beta cells,

which produce insulin.

In addition to the potential broad range of use, nuclear transplantation

therapy to create embryonic stem cells has many benefits -- the creation of

cells that are genetically matched to the patient, the repair of genetic

defects within cells to treat or cure inherited diseases, and the

possibility of growing embryonic stem cells in culture for continued therapy

as needed.

" Before the potential of nuclear transplantation therapy can be realized,

much more research about the basic biology of stem cells has to be done, "

says Daley.

Unexpectedly, the researchers confronted interesting biological principles,

which appear to be related to a fundamental difference between adults cells

and cells derived from embryonic stem cells, even when the two types of

cells are genetically identical.

" While these results show nuclear transplantation therapy can work in

principle, there are technical issues that we are working on now, " explained

Jaenisch.

The work from the Daley lab was supported by grants from the NIH, the

National Science Foundation, MIT Biotechnology Process Engineering Center,

the Canadian Institutes of Health Research and the Alberta Heritage

Foundation for Medical Research.

The work from the Jaenisch lab was supported by Boehringer Ingelheim Fonds

and the National Cancer Institute.

[Guest guest]

Im so sorry you had to go thru that J. I had a policeman come to the door this AM and she needed educated on NF too:( "But why do you speak so well??" Like im faking this for jollies, oh geez:)~~Lowi who thinks Jimmy would be a great spokeman:) Take a bow guy:!!!

RE: <no subject>

I had a similar experience, Pete. I had bad headaches in July and all I wanted was something to kill the pain, but it was midnight and we went to the emergency room at our local county hospital. Sheesh, big mistake. I told them I had tumors and they insisted on doing a CT scan and they were flabbergasted after they saw it. "Wow, you have brain tumors." Doh. I got home FINALLY at 6:30 am and was able to sleep for a whopping 45 mins before the pain hit again. WASTE of time!!! Thank goodness for the pain clinic! No hassles, just good drugs.

[Guest guest]

Im so sorry you had to go thru that J. I had a policeman come to the door this AM and she needed educated on NF too:( "But why do you speak so well??" Like im faking this for jollies, oh geez:)~~Lowi who thinks Jimmy would be a great spokeman:) Take a bow guy:!!!

RE: <no subject>

I had a similar experience, Pete. I had bad headaches in July and all I wanted was something to kill the pain, but it was midnight and we went to the emergency room at our local county hospital. Sheesh, big mistake. I told them I had tumors and they insisted on doing a CT scan and they were flabbergasted after they saw it. "Wow, you have brain tumors." Doh. I got home FINALLY at 6:30 am and was able to sleep for a whopping 45 mins before the pain hit again. WASTE of time!!! Thank goodness for the pain clinic! No hassles, just good drugs.

[Guest guest]

Im so sorry you had to go thru that J. I had a policeman come to the door this AM and she needed educated on NF too:( "But why do you speak so well??" Like im faking this for jollies, oh geez:)~~Lowi who thinks Jimmy would be a great spokeman:) Take a bow guy:!!!

RE: <no subject>

I had a similar experience, Pete. I had bad headaches in July and all I wanted was something to kill the pain, but it was midnight and we went to the emergency room at our local county hospital. Sheesh, big mistake. I told them I had tumors and they insisted on doing a CT scan and they were flabbergasted after they saw it. "Wow, you have brain tumors." Doh. I got home FINALLY at 6:30 am and was able to sleep for a whopping 45 mins before the pain hit again. WASTE of time!!! Thank goodness for the pain clinic! No hassles, just good drugs.