OBJECTIVES: Recent data show that Imatinib mesylate (IM) also affects haematopoietic stem cells (HSC), T lymphocytes and dendritic cells that do not harbour constitutively active tyrosine kinases. MATERIALS AND METHODS: We evaluated possible effects of IM on human bone marrow-derived mesenchymal stem cells (MSC) in vitro. RESULTS: Screening the activity of 42 receptor tyrosine kinases revealed an exclusive inhibition of platelet-derived growth factor receptorbeta (PDGFRbeta). Analysis of downstream targets of PDGFRbeta demonstrated IM-mediated reduction of Akt and Erk1/2 phosphorylation. Culture of MSC with IM led to the reversible development of perinuclear multi-vesicular bodies. The proliferation and clonogenicity of MSC were significantly reduced compared to control cultures. IM favoured adipogenic differentiation of MSC whereas osteogenesis was suppressed. The functional deficits described led to a 50% reduction in the support of clonogenic haematopoietic stem cells, cultured for 1 month on a monolayer of MSC with IM. CONCLUSION: In summary, inhibition of PDGFRbeta and downstream Akt and Erk signalling by IM has a significant impact on proliferation and differentiation of human MSC in vitro.
OBJECTIVES: Recent data show that Imatinib mesylate (IM) also affects haematopoietic stem cells (HSC), T lymphocytes and dendritic cells that do not harbour constitutively active tyrosine kinases. MATERIALS AND METHODS: We evaluated possible effects of IM on human bone marrow-derived mesenchymal stem cells (MSC) in vitro. RESULTS: Screening the activity of 42 receptor tyrosine kinases revealed an exclusive inhibition of platelet-derived growth factor receptorbeta (PDGFRbeta). Analysis of downstream targets of PDGFRbeta demonstrated IM-mediated reduction of Akt and Erk1/2 phosphorylation. Culture of MSC with IM led to the reversible development of perinuclear multi-vesicular bodies. The proliferation and clonogenicity of MSC were significantly reduced compared to control cultures. IM favoured adipogenic differentiation of MSC whereas osteogenesis was suppressed. The functional deficits described led to a 50% reduction in the support of clonogenic haematopoietic stem cells, cultured for 1 month on a monolayer of MSC with IM. CONCLUSION: In summary, inhibition of PDGFRbeta and downstream Akt and Erk signalling by IM has a significant impact on proliferation and differentiation of human MSC in vitro.
Authors: Martin Bornhäuser; Nicolaus Kröger; Rainer Schwerdtfeger; Karin Schafer-Eckart; Herbert G Sayer; Christoph Scheid; Mattias Stelljes; Joachim Kienast; Peter Mundhenk; Stefan Fruehauf; Michael G Kiehl; Hannes Wandt; Catrin Theuser; Gerhard Ehninger; Axel R Zander Journal: Eur J Haematol Date: 2006-01 Impact factor: 2.997
Authors: E M Horwitz; D J Prockop; L A Fitzpatrick; W W Koo; P L Gordon; M Neel; M Sussman; P Orchard; J C Marx; R E Pyeritz; M K Brenner Journal: Nat Med Date: 1999-03 Impact factor: 53.440
Authors: M F Pittenger; A M Mackay; S C Beck; R K Jaiswal; R Douglas; J D Mosca; M A Moorman; D W Simonetti; S Craig; D R Marshak Journal: Science Date: 1999-04-02 Impact factor: 47.728
Authors: T Illmer; M Schaich; U Platzbecker; J Freiberg-Richter; U Oelschlägel; M von Bonin; S Pursche; T Bergemann; G Ehninger; E Schleyer Journal: Leukemia Date: 2004-03 Impact factor: 11.528
Authors: Lysann Michaela Kroschwald; Josephine Tabea Tauer; Sonja Ingrid Kroschwald; Meinolf Suttorp; Anne Wiedenfeld; Stefan Beissert; Andrea Bauer; Martina Rauner Journal: Oncol Lett Date: 2019-06-21 Impact factor: 2.967
Authors: Jie Yu Ye; Godfrey Chi Fung Chan; Liang Qiao; Qizhou Lian; Fan Yi Meng; Xue Qun Luo; Levon M Khachigian; Ming Ma; Ruixia Deng; Jian Liang Chen; Beng H Chong; Mo Yang Journal: Haematologica Date: 2010-06-18 Impact factor: 9.941
Authors: Wei Yao; Min Guan; Junjing Jia; Weiwei Dai; Yu-An E Lay; Sarah Amugongo; Ruiwu Liu; David Olivos; Mary Saunders; Kit S Lam; Jan Nolta; Diana Olvera; Robert O Ritchie; Nancy E Lane Journal: Stem Cells Date: 2013-09 Impact factor: 6.277