Embryonic stem cells (ESC) seem to have the potential to become an alternative source of cells for bone marrow transplantation, with a new study showing that they can be used to created functional immune system blood cells.
The study, published online in journal Blood, offers new hope to patients with severe blood and immune disorders.
AdvertisementResearchers at the University of Iowa Hospitals and Clinics say that one of the biggest limitations of traditional transplants—which use bone marrow, umbilical cord blood, and peripheral blood from donors—is that the antigens on the surface of donated cells must be compatible with those of the patient to prevent rejection.
This is where the advantage of using embryonic stem cells comes into picture, say the researchers.
According to them, embryonic stem cells have low levels of these antigens and may therefore be less likely to provoke a defensive reaction by the patient's body. Thus, even when patients do not find suitably matched donors, they may still be able to receive transplants.
Previous studies had shown that mouse embryonic stem cells could be coaxed to form blood-forming hematopoietic cells by introducing into them a protein called HOXB4, known for its unique ability to greatly enhance cell proliferation.
In the latest study, a team of scientists from Iowa, Taiwan, and Germany used HOXB4-containing ESCs to engraft the bone marrow and rescue mice that genetically lacked any immune system and had been irradiated to destroy their bone marrow.
Only cells containing HOXB4 were able to engraft, rescue the mice, and produce blood cells long term. The engrafted cells were shown to be derived from the transplanted ESC-derived cells.
To determine whether the transplants were able to rebuild the defunct immune system, the scientists injected the mice with a common rodent virus called LCMV and watched for T-cell activity, a sign that the body was defending itself against the infection.
Although the number of T cells generated by the new hematopoietic cells was low, they were able to respond effectively to the virus. Besides, the transplanted hematopoietic cells were also able to produce B cells and other defensive cells called antigen-presenting cells, which have a role in signaling T cells to action.
The research team also tested the ability of the mice to respond to vaccination and demonstrated the induction of specific immune cells. Although the level of immune response was not what is seen in normal adult mice after exposure to the virus or vaccine, it was measurable and effective.
None of the 70 transplanted mice followed for more than 200 days developed any tumours, another concern when using ESCs for tissue regeneration.
"These results show, for the first time, that functional white blood cells, the key players in the body's immune system, can be successfully derived from embryonic stem cells expressing HOXB4," said lead study author Nicholas Zavazava, Professor of Internal Medicine and Director of Transplant Research at the University of Iowa Hospitals and Clinics in Iowa City and Staff Physician at the Iowa City VA Medical Center.
"Therefore, we're hopeful that these exciting findings are the first step toward new, improved therapies for patients," he added.