Mesenchymal stem cell populations and their role in the human hematopoietic niche

• Applicant: Dr. Ariane Tormin
• Subject Area: Cell Biology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213527094

Adult bone marrow contains two distinct populations of stem cells: hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). HSCs give rise to all blood lineages whereas MSCs differentiate towards mesenchymal lineages, including bone, fat, cartilage, and perivascular reticular cells. The hematopoietic system has a rapid turnover rate in adult bone marrow. Over-proliferation, and unnecessary differentiation of HSCs can lead to the development of leukemia. The hematopoietic microenvironment or niche regulates and controls everyday homeostasis. It also provides a shelter for HSCs and protects them from physiological stress, unnecessary differentiation and proliferation, and eventual exhaustion throughout the lifetime of an organism. MSCs and their progeny are thought to be involved in this niche and to be key regulators of bone marrow physiology. Particularly in the human system, the in vivo function and biology of MSCs and their contribution to the niche in normal and diseased bone marrow remains poorly understood. A better knowledge of the interactions between hematopoietic cells and the mesenchymal niche is pivotal to identifying potential new targets for therapies of hematopoietic diseases. The aim of this proposal is to study human bone marrow MSCs in vivo and investigate their role in the hematopoietic niche. In the proposed research plan, human MSCs will be quantified in normal and diseased bone marrow biopsies and their anatomical distribution will be analyzed and compared. In addition, the in situ expression of cytokines and HSC maintenance factors expressed by MSCs and the localization of hematopoietic stem and progenitor cells in relation to MSCs will be studied in healthy and diseased human bone marrow. Xeno-transplantation models will be used to investigate the potential of MSCs to create and maintain a niche, which allows the homing of HSC, and to study crucial interactions of human mesenchymal populations and human HSCs.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Leslie Silberstein