Wednesday, November 28, 2007

Transplants without tears

Transplants without tears
Science Magazine (subscription) - USA
... multiple sclerosis, and lupus, in which traditional conditioning was considered too drastic. "it's an intriguing new approach," says stem cell biologist ...
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Transplants Without Tears

By Mitch Leslie
ScienceNOW Daily News
26 November 2007

The image “file:///C:/Documents%20and%20Settings/Bill/My%20Documents/jokes/george%20bush%20videos/2007112621.jpg” cannot be displayed, because it contains errors. A new treatment might allow patients to avoid some of the grueling side effects of bone marrow transplants. Researchers reported in the 23 November issue of Science that they can use a specific type of antibody to clear away old marrow stem cells in mice, allowing fresh ones to take their place. The discovery could allow patients to receive bone marrow without undergoing chemotherapy and other toxic procedures.

Bone marrow transplants can ameliorate diseases such as sickle cell anemia by replenishing hematopoietic stem cells (HSCs) that spawn white and red blood cells. But before they receive this marrow, patients must typically undergo conditioning, a course of chemotherapy (and sometimes radiation) that wipes out immune cells that might attack the transplants and eliminates the existing, faulty HSCs. However, conditioning also devastates stem cells throughout the body, triggering hair loss, diarrhea, mental decline, and other side effects.

Searching for a gentler approach, postdoc Deepta Bhattacharya and immunologist Irving Weissman of the Stanford University School of Medicine in Palo Alto, California, and colleagues dosed mice with an antibody that ties up c-kit, a receptor on the surface of HSCs that promotes their division and survival. The antibody sent the number of HSCs in the animals' bone marrow plunging by more than 98% after 8 days, the researchers report. That seemed to clear space for new cells to rebuild the animals' immune systems. Six months after a bone marrow transplant, 90% of one type of immune cell were derived from transferred HSCs, the team found.

Weissman envisions that an HSC-removing antibody will be part of a two-pronged attack on illnesses such as sickle cell anemia, severe combined immunodeficiency, aplastic anemia, and thalassemia. First, patients would receive antibodies to suppress immune cells that might reject a bone marrow transplant; such antibodies are already in use, although they can cause flulike symptoms and other side effects. Then, an HSC-deleting antibody would make room for new stem cells. Weissman cautions, however, that researchers need to find a human antibody that performs as well as the mouse version. But if successful, the strategy could eliminate the need for chemotherapy and radiation and allow transplants for diseases, such as type 1 diabetes, multiple sclerosis, and lupus, in which traditional conditioning was considered too drastic.

"It's an intriguing new approach," says stem cell biologist and clinician David Scadden of Harvard Medical School in Boston, Massachusetts. But stem cell biologist Kateri Moore of Mount Sinai School of Medicine in New York City questions whether the antibody removes all HSCs. She notes that even without a transplant, HSC numbers rebound in mice within about 3 weeks of an antibody dose. Any HSCs spared by the antibody, she warns, could compete with newcomers for space or even produce T cells that attack the transplants.

Related site

More information on bone marrow transplants
http://sciencenow.sciencemag.org/cgi/content/full/2007/1126/2


Heading home.
A glowing stem cell transplant searches out a place to settle down.

Credit: Deepta Bhattacharya, Agnieszka Czechowicz, and Irving Weissman

__________________________________
Science 23 November 2007:
Vol. 318. no. 5854, pp. 1296 - 1299
DOI: 10.1126/science.1149726

Reports

http://www.sciencemag.org/cgi/content/abstract/318/5854/1296

Efficient Transplantation via Antibody-Based Clearance of Hematopoietic Stem Cell Niches -- Czechowicz et al. 318 (5854): 1296 -- Science

Agnieszka Czechowicz, Daniel Kraft, Irving L. Weissman,*{dagger}Deepta Bhattacharya{dagger}

Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. We provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host HSCs. Administration of ACK2, an antibody that blocks c-kit function, led to the transient removal of >98% of endogenous HSCs in immunodeficient mice. Subsequent transplantation of these mice with donor HSCs led to chimerism levels of up to 90%. Extrapolation of these methods to humans may enable mild but effective conditioning regimens for transplantation.

Institute of Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

{dagger} These authors contributed equally to this work.

* To whom correspondence should be addressed. E-mail: irv@stanford.edu

Read the Full Text



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a new hope for 'silent disease'
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... breakthrough ms drug called tysabri. the drug is aimed at reducing relapses and slowing the progression of disability in relapsing ms. while mrs hebberd ...
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Hello Bill,

Thank you so much for your email. The enrollment criteria for the Phase I/II trial for Chondrogen allowed patients 18-60 years of age.

If you require any additional information or have any other questions, please don't hesitate to contact me.

Sincerely,

Erica

Erica Elchin

Phone: 443.545.1824
Fax: 443.545.1701
www.osiris.com

7015 Albert Einstein Drive
Columbia, MD 21046

________

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