Improving Cord Blood Stem Cell Transplantation for Patients with Various Blood Diseases
A team of researchers developed the first successful laboratory culture system for increasing or expanding the numbers of cord blood stem cells in order to shorten the time necessary for complete engraftment for bone marrow transplantation. Umbilical cord blood is a source of blood-forming cells used in transplants. However, its utility is restricted due to the relatively small number of stem cells in a unit of cord blood. Because of this limitation, compared with a conventional bone marrow transplant, cord blood transplants take longer to fully repopulate all the different types of blood cells in the body. The longer timeframe for engraftment places the patient at increased risk of acquiring life-threatening infections, owing to the inadequate number of white blood cells. For this reason, cord blood is used more often in patients with a small body size, for example children, as they require fewer cells. Patients with larger bodies may have to be transplanted with two or more units of cord blood and still may contend with engraftment times longer than conventional bone marrow transplant.
The investigators took advantage of their knowledge of the “Notch” signaling pathway which stimulates expansion (cell division) of stem cells. A protein was engineered in the laboratory that activates the Notch pathway. The protein was used to stimulate expansion of cord blood stem cells in culture. The presence of the protein resulted in a greater than 100-fold increase in cultured cord blood stem cells compared with cells grown in the absence of the protein.
The researchers then conducted a pilot study of 10 patients with leukemia to begin to assess the safety of infusing cord blood stem cells that had been expanded in the laboratory with this Notch-mediated procedure and to perform an initial evaluation of the engraftment properties of the expanded stem cells. Each patient received two units of cord blood—one unit of non-expanded blood and one containing expanded blood cells that had been expanded with this procedure or two units of non-expanded blood. In this small group of patients, the investigators reported that they did not encounter safety issues. The median time for engraftment using the expanded cells was 16 days versus 26 days when non-expanded units of cord blood were used.
The study’s intriguing results suggest that engraftments derived from expanded cells may proceed more rapidly than those derived using conventional (non-expanded) cord blood. These results need to be followed up by a larger study in order to develop statistically significant results.
Delaney C, Heimfeld S, Brashem-Stein C, Voorhies H, Manger RL, and Bernstein ID. Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 16: 232-237, 2010.