Many cancer patients who are candidates for high dose chemotherapy do not have available a suitable related or unrelated donor of bone marrow or peripheral blood progenitor cells. Human umbilical cord blood (CB) is a unique source of transplantable hematopoietic cells that offers an alternative source of hematopoietic cells for these patients. The use of CB cells to date, has primarily been limited to small pediatric patients due to the low cell numbers in CB products. The focus of this proposal is to optimize ex vivo culture of CB to provide increased numbers of cells to enable the use of CB in adult patients. In addition, optimization of the expansion cultures will enable more rapid hematopoietic and immune recovery post transplant and potentially minimize other complications associated with transplantation of CB.
The first aim of these studies is to evaluate improved expansion culture conditions in clinical trials. Preclinical studies will also be performed to evaluate other culture conditions that may provide enhanced platelet recovery. In addition, analysis will be performed of primitive cells in the expanded products as an indication of the effect of expansion on long term engrafting cells (stem cells).
The second aim will optimize transduction cultures of expanded cells and subsequent clinical studies will incorporate these conditions to use marked expanded cells in patients. This will allow the evaluation of the contribution of expanded cells to long to engraftment. Correlative analysis will be performed comparing the contribution of the marked cells in patients with in vitro assays of primitive progenitor cells to determine the predictive value of the in vitro assays.
The third aim will evaluate the immune recovery in patients receiving ex vivo expanded cells. Both phenotypical and functional analysis of T cells subsets will be performed The final goal of these studies is to determine culture conditions for the expansion of T cells in vitro for use a source of donor lympohocytes to induce an anti tumor effect in patients who relapse. In the absence of cultured T cells the patients who relapse have no alternate source of donor lymphocytes and would die from disease progression. The outcome of these studies will provide us with a better understanding of the potential clinical utility of CB. Optimal expansion cultures will enable the use of CB in adults and provide more rapid engraftment. Overall these studies will lead to improved outcome in these patients.
| Wang, Y; Huso, D L; Harrington, J et al. (2005) Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy 7:509-19 |
| Shpall, Elizabeth J; Quinones, Ralph; Giller, Roger et al. (2002) Transplantation of ex vivo expanded cord blood. Biol Blood Marrow Transplant 8:368-76 |
| McNiece, Ian K; Almeida-Porada, Graca; Shpall, Elizabeth J et al. (2002) Ex vivo expanded cord blood cells provide rapid engraftment in fetal sheep but lack long-term engrafting potential. Exp Hematol 30:612-6 |
