The goal of this R24 application is to establish a resource that will provide clinical grade reagents and methods for ex vivo expansion of human hematopoietic repopulating cells to improve cord blood transplantation. Umbilical cord blood has been established as an alternative source of stem cells for patients in need of stem cell transplantation who do not have an otherwise suitable donor identified. However, results have been limited due to inadequate stem cell numbers, leading to delayed engraftment that is often associated with lethal infection. Recently, our laboratory has developed novel methods, using Noth ligan, a known regulator of cell fate determination, to enhance the repopulating capacity of cord blood precursor cells. Thus, to extend these findings into the clinic and provide a resource for future clinical trials, we propose to optimize these methods for expanding cord blood precursor cells, and to develop cGMP compliant procedures methods and prepare the clinical grade reagents necessary for clinical trials. Successful completion of these aims will provide the basis for future efforts to establish the feasibility and safety of our approach in a phase I clinical trial, and then to provide the cGMP reagents and procedures as a resource for multi-institutional phase II and III trials.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Resource-Related Research Projects (R24)
Project #
1R24HL074445-01
Application #
6684547
Study Section
Special Emphasis Panel (ZHL1-CSR-B (M2))
Program Officer
Mondoro, Traci
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$805,500
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Milano, Filippo; Chien, Jason W; Riffkin, Ivy et al. (2012) Stable long-term pulmonary function after myeloablative double cord blood transplant. Biol Blood Marrow Transplant 18:309-13
Milano, Filippo; Pergam, Steven A; Xie, Hu et al. (2011) Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients. Blood 118:5689-96
Dahlberg, Ann; Delaney, Colleen; Bernstein, Irwin D (2011) Ex vivo expansion of human hematopoietic stem and progenitor cells. Blood 117:6083-90
Delaney, Colleen; Heimfeld, Shelly; Brashem-Stein, Carolyn et al. (2010) Notch-mediated expansion of human cord blood progenitor cells capable of rapid myeloid reconstitution. Nat Med 16:232-6
Gutman, Jonathan A; Turtle, Cameron J; Manley, Thomas J et al. (2010) Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit. Blood 115:757-65
Watts, Korashon L; Delaney, Colleen; Humphries, R Keith et al. (2010) Combination of HOXB4 and Delta-1 ligand improves expansion of cord blood cells. Blood 116:5859-66
Delaney, Colleen; Varnum-Finney, Barbara; Aoyama, Keisuke et al. (2005) Dose-dependent effects of the Notch ligand Delta1 on ex vivo differentiation and in vivo marrow repopulating ability of cord blood cells. Blood 106:2693-9