• REHOVOT, Israel - February 5, 1999 - In bone marrow transplantation, a patient receives a transfusion of stem cells, which migrate to the patient's bone marrow and start producing new, healthy blood. (weizmann.ac.il)
  • But many transplants fail because, usually, very few stem cells make their way from the blood circulation into the recipient's marrow. (weizmann.ac.il)
  • Furthermore, the scientists managed to dramatically increase the proportion of stem cells capable of migrating to the marrow. (weizmann.ac.il)
  • The research was conducted in immunodeficient mice transplanted with human stem cells. (weizmann.ac.il)
  • In a transplantation, the patient's malignant or defective marrow is destroyed, and healthy stem cells are transfused intravenously into the circulation in the hope that they will find their way to the patient's bones and create normal marrow. (weizmann.ac.il)
  • The Weizmann Institute scientists found that only human stem cells equipped with a certain type of receptor, called CXCR4, migrated from the circulation to the bone marrow of experimental mice. (weizmann.ac.il)
  • It is this molecular "attractor" which guides human stem cells through the blood vessel walls into the marrow cavities. (weizmann.ac.il)
  • similarly, stem cells will migrate to the bone marrow only if they display a specific receptor on their surface that allows them to pick up the signals from marrow cells. (weizmann.ac.il)
  • Stem cell migration illustration available in color) The researchers found, however, that only a small number of human stem cells display the CXCR4 receptor on their surface, a fact that explains why so few stem cells are successfully transplanted - patients typically wind up with only 10% of the normal number of these cells. (weizmann.ac.il)
  • According to this theory, stem cells that entered the marrow cavity "disappeared" because, instead of proliferating, they quickly matured into the various types of blood cells. (weizmann.ac.il)
  • The new study, however, suggests that stem cells may also "disappear" because they lack the CXCR4 receptor and therefore fail to migrate to the recipient's marrow. (weizmann.ac.il)
  • In the Weizmann study, this technique increased the number of successfully transplanted, functional human stem cells from 25 percent to greater than 90 percent. (weizmann.ac.il)
  • In the future, it may be possible to predict the success of a bone marrow transplantation by evaluating the highly variable proportion of the patient's stem cells that express the CXCR4 receptor. (weizmann.ac.il)
  • In a recent study using a mouse model for OI generated at the NICHD, researchers and their colleagues characterized the differentiation of bone marrow stem cells in adult mice into other cell types. (nih.gov)
  • They found that the ability of the stem cells to turn into bone cells was impaired, shunting the precursor cells into the pathway to become fat cells. (nih.gov)
  • Treating the OI mouse model with Btz improved the capacity for bone marrow stem cells to turn into bone cells and improved whole bone properties. (nih.gov)
  • Although Btz itself is not a suitable therapy for OI, given these study findings, future research may target bone marrow stem cells as an approach to treat OI. (nih.gov)
  • One potential treatment, sclerostin antibody (Scl-Ab) therapy, improved bone mass in mice. (nih.gov)
  • Over the past several years, NICHD researchers from the Section of Physical Biochemistry (SPB) and the Section on Heritable Disorders of Bone and Extracellular Matrix, along with university colleagues, have suggested that transplanting healthy bone marrow into mice with OI may someday lead to an effective treatment for people. (nih.gov)
  • In 2009, a group published the results of a study in which bone marrow was transplanted in utero to mice with lethal OI mutations. (nih.gov)
  • Bone marrow transplantation is a last-resort treatment that saves the lives of many patients with leukemia and other malignancies and blood disorders. (weizmann.ac.il)
  • NICHD researchers from the Section on Heritable Disorders of Bone and Extracellular Matrix are conducting clinical studies of a bisphosphonate drug called pamidronate in children who have type III or type IV OI. (nih.gov)
  • Section on Heritable Disorders of Bone and Extracellular Matrix researchers are recruiting patients for a long-term study of types III and IV OI from birth to age 25. (nih.gov)
  • NICHD researchers are exploring additional therapies for treating OI, including medications that build bone mass. (nih.gov)
  • Researchers then treated the OI mouse model with bortezomib (Btz), which the Food and Drug Administration has approved for treating a cancer (myeloma) that begins in certain bone marrow cells. (nih.gov)
  • In a study published in the February 5 issue of Science , a research team headed by Dr. Tsvee Lapidot of Weizmann Institute's Immunology Department has revealed key elements of the mechanism responsible for stem cell migration from circulating blood to the bone marrow. (weizmann.ac.il)