Model-Based Analysis and Modulation of Stem Cell Renewal on Biomimetic Supports

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The objective of this project is to understand the role of growth factors and bioreactor design on the in vitro culture of hematopoietic tissues, with a goal of producing cells outside of the body for use in bone marrow reconstruction and gene therapy. The Principal Investigators (PIs) propose a technique to increase the expansion (division) of stem cells ex vivo. Stem cells are typically found in the bone marrow, and after differentiation are responsible for creation of mature blood cells (hematopoiesis). The PIs hypothesize that membrane bound stem cell factor (bSCF) will result in enhanced stem cell renewal ex vivo, and that will occur because bSCF (and associated receptor, c-kit) will not be internalized by the stem cells. There are four specific aims to test this hypothesis which include: (1) covalently bind SCF to a non-cell-adhesive polymer support; (2) study the effect of bSCF and soluble SCF (sSCF) on model cells, the human-cytokine-dependent cell line M07e; (3) model the growth of M07e cells (with bSCF and sSCF) to determine growth/death rates, and the fraction of c-kit receptors occupied by SCF, and (4) repeat these steps with human stem cells removed from cancer patients.