Mechanism of dynamic homing and migration of human hematopoietic stem cells in the bone marrow niche using quantitative tools (B07)

Subject Area Hematology, Oncology
Term from 2010 to 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 122491522
 

Project Description

Stem cell functions are determined and influenced by their physical interactions with the niche. In this project, we will quantify the mechanical interactions of healthy hematopoietic stem cells (HSC) and stem cells from leukemia patients with the bone marrow niche. The underlying hypothesis is that leu-kemia initiating cells could be eliminated by understanding the mechanistic and functional differences in stem cell-niche interactions. Utilizing unique quantitative tools, such as functionalized surrogate sur-faces, hydrogel substrates with tunable elasticity, high throughput microscopy, and dynamic phenotyping of active deformation and motion, we will follow three specific aims: (1) biological impacts of ex-trinsic factors on adhesion and migration of HSC, (2) influence of 3D niche mechanics on HSC-MSC interactions, and (3) biological impacts of intrinsic factors, such as aging, on adhesion and migration of HSC.
DFG Programme Collaborative Research Centres
Subproject of SFB 873:  Maintenance and Differentiation of Stem Cells in Development und Disease
Major Instrumentation Optical trap system
Instrumentation Group 4660 Mikromanipulatoren, Elektrodenziehgeräte, Mikroschmieden
Applicant Institution Ruprecht-Karls-Universität Heidelberg
Project Heads Professor Dr. Sascha Dietrich; Professor Dr. Motomu Tanaka