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 Projects 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
von Bonin M, Bornhäuser M
The bone marrow niche as a target of GvHD.
Stem Cells. 32(6):1420–8 (2014)
Prewitz MC, Seib FP, von BM, Friedrichs J, Stissel A, Niehage C, Muller K, Anastassiadis K, Waskow C, Hoflack B, Bornhäuser M, Werner C
Tightly anchored tissue-mimetic matrices as instructive stem cell microenvironments.
Nat Methods. 10:788–94 (2013)
Duryagina R, Thieme S, Anastassiadis K, Werner C, Schneider S, Wobus M, Brenner S, Bornhäuser M
Overexpression of Jagged-1 and its intracellular domain in human mesenchymal stromal cells differentially affect the interaction with hematopoietic stem and progenitor cells.
Stem Cells Dev. 22:2736–50 (2013)
Bornhäuser M, Kienast J, Trenschel R, et al
Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial.
Lancet Oncol. 13:1035–44 (2012)
Bornhäuser M, Thiede C, Platzbecker U, Kiani A, Oelschlaegel U, Babatz J, Lehmann D, Holig K, Radke J, Tuve S, Wermke M, Wehner R, Jahnisch H, Bachmann MP, Rieber EP, Schetelig J, Ehninger G, Schmitz M
Prophylactic transfer of BCR-ABL-, PR1-, and WT1-reactive donor T cells after T cell-depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia.
Blood. 117:7174–84 (2011)