Cryocord - Expansion of Cord Blood Stem Cells Found To Be Feasible

Expansion of Cord Blood Stem Cells Found To Be Feasible

ne of the major limitations of umbilical cord stem cell transplantation is the relative low volume of stem cells harvested from the placenta. Because of this problem, transplantation is generally only feasible for children or small adults. Technology to expand these umbilical cord blood stem cells has now been developed and results were reported at the American Society of Hematology in December 1999. In an abstract by Jaroscak, umbilical cord blood was treated with a number of growth factors, in the Aastrom Replicell system for large scale expansion, in order to expand the total number of cells, as well as CD 34 positive cells, which are thought to represent the stem cell responsible for blood cell development. Data from this group showed that CD 34 positive cells could be expanded dramatically with the proper combination or growth factors. Similarly, Kogler and colleagues from Germany were also able to dramatically expand cord blood cells, an d in particular CD 34 positive cells with commercially available growth factors. These data clearly suggest that stems can be readily expanded using available technologies.

Another group at the Western Pennsylvania Cancer Center attempted to engraft mice with human umbilical cord blood cells to determine whether or not further expansion could take place after these cells had undergone expansion in the (test tube). There data confirmed that expanded human CD 34 positive cord blood stem cells had functional activity. Similar results were obtained by Goltry at the University of Massachusetts. Again, cord blood cells were subjected to growth factor and clinical scale expansions in the AastromReplicell production system. These cells were then given to mice with further expansion of the human cells. These results further confirm that cord blood cells generated in a clinical expansion model have the ability to engraft mice.

Expansion of cord blood cells has also been performed successfully for human use as well. Kurtzberg and colleagues at Duke University infused unstimulated umbilical cord blood cells into patients undergoing transplantation for Leukemia, as well as non-malignant diseases. Expanded cells were infused as a boost to the conventional graft during the transplantation process using the same AastromReplicell system. Those patients who received expanded cells had superior survival at 100 days after transplant when compared to historical controls receiving similar doses of unstimulated cells. Further testing is under way at the center.

Adult and pediatric cancer patients have been rescued with cord blood stem cells that have been expanded at the University of Colorado. Dr. Shapall and others treated nineteen patients with umbilical cord blood stem cells. One group of patients received 60% of the cord blood product, while the other 40% was expanded with growth factors and infused ten days after the initiation of the transplant process. The second group of patients had 40% of the cord blood thawed prior to transplantation and expanded so that both growth factor stimulated and non-stimulated were infused that the beginning of the transplantation protocol. There was a 0% white blood cell engraftment failure rate which is lower than the traditional 125-60% failure rate reported for unexpanded cord blood transplants. In addition, the time to white blood cell and platelet engraftment in adult patients were comparable to pediatric patients. Additional patients are being accrued to the study in order to determine the efficie ncy in toxicity of this expanded cord blood product.

Although research in this area is still ongoing, it appears that cord blood expansion is feasible and will make it practical to treat adult patients with expanded cord blood product. This will further broaden the applicability of cord blood transplantation.

References:

Augmentation of Umbilical Cord Blood (UCB) Transplantation With X-Vivo Expanded Cells, a phase 1 trial using the AastromReplicell system, Joanne Kurtzberg, et. al, abstract 2547, Blood, Volume 94, No. 10

The Effect of Cytokine Combinations on the Clinical Scale, X-Vivo Expansion of Umbilical Blood, J. Jarosek, abstract 2556, Blood, Volume 94, No. 10

Comparison of Two Clinically Feasible Methods for X-Vivo Expansion of Committed Hematopietic Progenitor Cells from Cord Blood, Jesine Kogler, abstract 2558,Blood, Volume 94, No. 10, supplement 1.

Functional Activity of X-Vivo Expanded Human CD 34+ Cord Blood stem Cells, G. L. Gilmore, abstract 3122, Blood, Volume 94, No. 10 supplement 1.

Transplantation of Adult and Pediatric Cancer Patients with Cord Blood Progenitors Expanded X-Vivo, Elizabeth J. Shpall, abstract 3145, Blood Volume 94, No. 10, Supplement 1.

X-Vivo Expanded Cord Blood Cells Generated in aClinical-Scale Perfusion Culture System are Capable of Engrafting NOD-SCID mice, K.L. Goltry, abstract 4776, Blood, Volume 94 No. 10, supplement 1.