Martin Bornhäuser

Biology of adult stem cells: clinical relevance for leukemia and stem cell transplantation

Previous and current research

Isolation and characterization of mesenchymal adult bone marrow stem cells (MSC) and hematopoietic stem cells (HSC) from healthy donors and patients with leukemia. Characterization of functional potency and description of stem cell niches. Interaction of stem cells with extracellular matrix and artificial scaffolds.

Mesenchymal adult bone marrow stem cells (MSC)
Mesenchymal stem cells (MSC) have been identified in the bone marrow (BM) as multipotent non-hematopoietic progenitor cells that differentiate into osteoblasts, adipocytes, chondrocytes, tenocytes, skeletal myocytes, and cells of visceral mesoderm1-3. MSC do not express hematopoietic markers, but a specific pattern of molecules, such as SH2 (CD105), SH3, SH4 (CD73) and STRO-1. MSC interact with hematopoietic stem cells (HSC), influencing their homing and differentiation through cell-cell contact and the production of factors and chemokines. We have specifically studied the potential of endothelial differentiation of MSC and the impact of a tyrosine kinase inhibitor (Imatinib mesylate) on this type of stem cells.

Hematopoietic stem cells (HSC)
Hematopoietic stem cells express the markers CD34 and CD133 and can repopulate a myeloablated recipient after allogeneic or autologous transplantation. Besides their clinical use, we are interested in the biology of hematapoietic stem cells in-vitro and in-vivo. Hematopoietic stem cells from various sources (bone marrow, cord blood and peripheral blood) are isolated and characterized by phenotyping and gene expression studies. One major effort is to expand stem cells ex-vivo using various culture conditions.
A major focus is the characterization of homing of hematopoietic stem cells to specific niches from which they can be mobilized or start differentiating. For this purposes animal models and specific coculture systems have been developed.

Future prospects and goals

• Use engineered MSC to generate stem cell niches in-vitro.
• Study the role of osteogenic differentiation of MSC for the support of HSC
• Generate artifical stem cell niches using material science

About

1993-1994: University Hospital, Tübingen, Germany 1994: Stem Cell Laboratory, Department for Pediatrics, Tübingen 1995-2005: Internship, University Hospital, Dresden, Germany since 2004: Head of Stem Cell Transplant Program, University Hospital, Dresden

Selected publications

Bornhäuser,M., Eger,L., Oelschlaegel,U., Auffermann-Gretzinger,S., Kiani,A., Schetelig,J., Illmer,T., Schaich,M., Corbeil,D., Thiede,C., Ehninger,G. (2005): Rapid reconstitution of dendritic cells after allogeneic transplantation of CD133+ selected hematopoietic stem cells. Leukemia 19, 161-165.

Oswald,J., Boxberger,S., Jorgensen,B., Feldmann,S., Ehninger,G., Bornhäuser,M., Werner,C. (2004): Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 22, 377-384.

Bornhäuser,M., Storer,B., Slattery,J.T., Appelbaum,F.R., Deeg,H.J., Hansen,J., Martin,P.J., McDonald,G.B., Nichols,W.G., Radich,J., Woolfrey,A., Jenke,A., Schleyer,E., Thiede,C., Ehninger,G., Anasetti,C. (2003): Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood 102, 820-826.

Kohler,T., Plettig,R., Wetzstein,W., Schaffer,B., Ordemann,R., Nagels,H.O., Ehninger,G., Bornhäuser,M. (1999): Defining optimum conditions for the ex vivo expansion of human umbilical cord blood cells. Influences of progenitor enrichment, interference with feeder layers, early-acting cytokines and agitation of culture vessels. Stem Cells 17, 19-24.

Oswald J, Steudel C, Salchert K, Joergensen B, Thiede C, Ehninger G, Werner C, Bornhäuser M.: Gene Expression Profiling of CD34+ Hematopoietic Cells Expanded in a Collagen I Matrix. Stem Cells 2005, epub September 15.

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