TY  - JOUR
A1  - Ascheid, David
A1  - Baumann, Magdalena
A1  - Funke, Caroline
A1  - Volz, Julia
A1  - Pinnecker, Jürgen
A1  - Friedrich, Mike
A1  - Höhn, Marie
A1  - Nandigama, Rajender
A1  - Ergün, Süleyman
A1  - Nieswandt, Bernhard
A1  - Heinze, Katrin G.
A1  - Henke, Erik
T1  - Image-based modeling of vascular organization to evaluate anti-angiogenic therapy
JF  - Biology Direct
N2  - In tumor therapy anti-angiogenic approaches have the potential to increase the efficacy of a wide variety of subsequently or co-administered agents, possibly by improving or normalizing the defective tumor vasculature. Successful implementation of the concept of vascular normalization under anti-angiogenic therapy, however, mandates a detailed understanding of key characteristics and a respective scoring metric that defines an improved vasculature and thus a successful attempt. Here, we show that beyond commonly used parameters such as vessel patency and maturation, anti-angiogenic approaches largely benefit if the complex vascular network with its vessel interconnections is both qualitatively and quantitatively assessed. To gain such deeper insight the organization of vascular networks, we introduce a multi-parametric evaluation of high-resolution angiographic images based on light-sheet fluorescence microscopy images of tumors. We first could pinpoint key correlations between vessel length, straightness and diameter to describe the regular, functional and organized structure observed under physiological conditions. We found that vascular networks from experimental tumors diverted from those in healthy organs, demonstrating the dysfunctionality of the tumor vasculature not only on the level of the individual vessel but also in terms of inadequate organization into larger structures. These parameters proofed effective in scoring the degree of disorganization in different tumor entities, and more importantly in grading a potential reversal under treatment with therapeutic agents. The presented vascular network analysis will support vascular normalization assessment and future optimization of anti-angiogenic therapy.
KW  - vascular structure
KW  - cancer
KW  - tumor microenvironment
KW  - optical clearing
KW  - light sheet fluorescence microscopy
KW  - 3D image analysis
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357242
VL  - 18
ER  - 
TY  - JOUR
A1  - Stegner, David
A1  - van Eeuwijk, Judith M.M.
A1  - Angay, Oğuzhan
A1  - Gorelashvili, Maximilian G.
A1  - Semeniak, Daniela
A1  - Pinnecker, Jürgen
A1  - Schmithausen, Patrick
A1  - Meyer, Imke
A1  - Friedrich, Mike
A1  - Dütting, Sebastian
A1  - Brede, Christian
A1  - Beilhack, Andreas
A1  - Schulze, Harald
A1  - Nieswandt, Bernhard
A1  - Heinze, Katrin G.
T1  - Thrombopoiesis is spatially regulated by the bone marrow vasculature
JF  - Nature Communications
N2  - In mammals, megakaryocytes (MKs) in the bone marrow (BM) produce blood platelets, required for hemostasis and thrombosis. MKs originate from hematopoietic stem cells and are thought to migrate from an endosteal niche towards the vascular sinusoids during their maturation. Through imaging of MKs in the intact BM, here we show that MKs can be found within the entire BM, without a bias towards bone-distant regions. By combining in vivo two-photon microscopy and in situ light-sheet fluorescence microscopy with computational simulations, we reveal surprisingly slow MK migration, limited intervascular space, and a vessel-biased MK pool. These data challenge the current thrombopoiesis model of MK migration and support a modified model, where MKs at sinusoids are replenished by sinusoidal precursors rather than cells from a distant periostic niche. As MKs do not need to migrate to reach the vessel, therapies to increase MK numbers might be sufficient to raise platelet counts.
KW  - bone marrow
KW  - megakaryocytes
KW  - thrombopoiesis
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170591
VL  - 8
IS  - 127
ER  -