A new discovery of a dictator molecule that governs the migration of blood stem cells to the bone marrow, resulting in subsequent production of blood cell components and immune stem cells could hold the key to the development of more effective stem cell therapy for malignant and non-malignant conditions in the future.
"This is another remarkable example of how bone and bone marrow interact. A receptor known to participate in the body's regulation of calcium and bone also is critical for stem cells to engraft in the bone marrow and regenerate blood and immune cells", said David Scadden, one of the senior researchers.
"It reminds us how tissues interact and how looking closely at where stem cells reside may tell us a lot about how to manipulate them", he added. Bone marrow transplantation is a life saving treatment option for a number of people suffering from hematological malignancies and other condition such as sickle cell anemia and thalassemia.
The hematopoietic stem cells that have a remarkable regenerative capacity play a very critical role in the production of blood cell components such as the red blood cell, white blood cell and platelets. It also governs the production of various cellular components of the immune system. More than 10 million of these cells are being produced everyday.
The success of bone marrow transplantation lies in the direction of the obtained stem cells from the donor (through bone marrow aspiration) to a specific region such as the brain or bone marrow to induce renewal and recovery. The stem cell preparation is usually administered in the form of an intravenous infusion.
The stem cells are usually found in the peripheral layer, close to the inner surface of the bone, within the bone marrow cavity. Previous studies had already established that the stem cells are regulated by the adjacent bone forming cells (osteoblasts) to some degree. Hence it is quite probable that factors that influence bone formation could play a role in the migration of blood stem cells to the bone marrow.
Based on this assumption, the researchers analyzed the effects of a calcium receptor (CaR, necessary for absorption of extracellular calcium and bone growth) on stem cell migration. Studies conducted on transgenic animal models found out that the receptor played a very crucial role in the blood stem cell migration as expected.
Transgenic mice that had deficient CaR receptors had low levels of blood stem cells. This observation was only seen in CaR receptor, proving the potential role played by these molecules in migration of stem cells. The production of stem cells by the fetal liver was found to be independent of the absence of the calcium receptor. Furthermore, mice with reduced levels of the Car receptor were found to have a poor adherence to collagen I, a bone specific protein conducted by osteoblasts.
"Since there are already drugs available that target this receptor, we may be able to quickly adapt these findings in animals to the treatment of human patients", concluded Dr. Scadden.