Accession Number:

ADA583988

Title:

Redefining the Hematopoietic Microenvironment

Descriptive Note:

Final rept. 30 Sep 2011-29 Mar 2013

Corporate Author:

FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA

Personal Author(s):

Report Date:

2013-04-01

Pagination or Media Count:

18.0

Abstract:

Hematopoietic stem cells HSC and their progeny reside in specialized niches of the microenvironment ME in the bone marrow. The ME niches control HSC self-renewal, differentiation, and maturation. The ME niche cells are derived from non-hematopoietic cells, including fibroblasts, osteoblastic and endothelial cells. Macrophages, which are hematopoietic in origin, are also a critical component of the ME niches, and can influence the function of the ME niche cells. I hypothesize that the macrophages can acquire defects that may compromise ME function and lead to bone marrow failure. To test this hypothesis, I proposed to develop a new in vivo model that allows the inducible depletion of the macrophages in dogs, followed by the documentation of marrow failure, and subsequent therapeutic interventions. At this period, I achieved 4 goals 1 Optimize culture conditions for generating dog macrophages, 2 Optimize transduction efficiency of a macrophage-specific CD163 promoter construct in dog CD34 HSC and test its macrophage-specific expression, 3 Establish a luciferase reporter assay to test the macrophage-specific promoter activity, and 4 Generate multiple lentiviral vectors containing the doghuman CD163 promoter, iCasp9, and p140MGMT constructs.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE