Heading home.
A glowing stem cell transplant searches out a place to settle down.
Credit: Deepta Bhattacharya, Agnieszka Czechowicz, and Irving Weissman
Posted on 11/27/2007 11:19:37 PM PST by neverdem
Heading home.
A glowing stem cell transplant searches out a place to settle down.
Credit: Deepta Bhattacharya, Agnieszka Czechowicz, and Irving Weissman
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.
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This is big news!
N.B. All of the host's immune system was not eliminated, so the problem of host versus graft disease is still a problem, not to mention graft versus host disease for possible type 1 diabetes transplants in the future, if they can solve all the problems.
Diabetics have been considered as immunocompromised for almost 20 years at the least, IMHO.
Man Who Helped Start Stem Cell War May End It
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Right now I have a friend undergoing a stem cell transplant of her own stem cells.
Only adult stem cells harvested from the same patient have avoided the necessity of immunosuppressant drugs so far, IMHO. There are or were about six dozen different diagnoses that have FDA approval for therapy or trial status with adult stem cells.
It appears that all studies with embryonic stem cells use immunosuppressant drugs or specially bred mice with severe combined immuno deficiency(SCID).
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