Claudio Vinegoni, Ph.D. | Imaging the Vascular Bone Marrow Niche During Inflammatory Stress

Circ.Res.
Imaging the Vascular Bone Marrow Niche During Inflammatory Stress

Vandoorne, K., Rohde, D., Kim, H. Y., Courties, G., Wojtkiewicz, G., Honold, L., Hoyer, F. F., Frodermann, V., Nayar, R., Herisson, F., Jung, Y., Desogere, P. A., Vinegoni, C., Caravan, P., Weissleder, R., Sosnovik, D. E., Lin, C. P., Swirski, F. K., and Nahrendorf^#, M.

Circulation Research 2018

ABS URL PMID DOI PMCID CITE HTML PDF

Rationale: Inflammatory stress induced by exposure to bacterial lipopolysaccharide causes hematopoietic stem cell expansion in the bone marrow niche, generating a cellular immune response. As an integral component of the hematopoietic stem cell niche, the bone marrow vasculature regulates the production and release of blood leukocytes, which protect the host against infection but also fuel inflammatory diseases. Objective: We aimed to develop imaging tools to explore vascular changes in the bone marrow niche during acute inflammation. Methods and Results: Using the TLR (Toll-like receptor) ligand lipopolysaccharide as a prototypical danger signal, we applied multiparametric, multimodality and multiscale imaging to characterize how the bone marrow vasculature adapts when hematopoiesis boosts leukocyte supply. In response to lipopolysaccharide, ex vivo flow cytometry and histology showed vascular changes to the bone marrow niche. Specifically, proliferating endothelial cells gave rise to new vasculature in the bone marrow during hypoxic conditions. We studied these vascular changes with complementary intravital microscopy and positron emission tomography/magnetic resonance imaging. Fluorescence and positron emission tomography integrin alpha V beta 3 imaging signal increased during lipopolysaccharide-induced vascular remodeling. Vascular leakiness, quantified by albumin-based in vivo microscopy and magnetic resonance imaging, rose when neutrophils departed and hematopoietic stem and progenitor cells proliferated more vigorously. Conclusions: Introducing a tool set to image bone marrow either with cellular resolution or noninvasively within the entire skeleton, this work sheds light on angiogenic responses that accompany emergency hematopoiesis. Understanding and monitoring bone marrow vasculature may provide a key to unlock therapeutic targets regulating systemic inflammation.
@article{2018-CIRCRES, author= {Vandoorne, K. and Rohde, D. and Kim, H. Y. and Courties, G. and Wojtkiewicz, G. and Honold, L. and Hoyer, F. F. and Frodermann, V. and Nayar, R. and Herisson, F. and Jung, Y. and Desogere, P. A. and Vinegoni, C. and Caravan, P. and Weissleder, R. and Sosnovik, D. E. and Lin, C. P. and Swirski, F. K. and Nahrendorf<sup>#</sup>, M.}, title= {Imaging the Vascular Bone Marrow Niche During Inflammatory Stress}, journal= {Circulation Research}, alternatejournal = {Circ.Res.}, year = {2018}, volume = {123}, number = {4}, pages = {415-427}, issn = {0009-7330}, doi = {10.1161/circresaha.118.313302}, pmcid = {6202141}, pmid= {29980569} }
29980569

6202141

10.1161/circresaha.118.313302

Abstract

"Rationale: Inflammatory stress induced by exposure to bacterial lipopolysaccharide causes hematopoietic stem cell expansion in the bone marrow niche, generating a cellular immune response. As an integral component of the hematopoietic stem cell niche, the bone marrow vasculature regulates the production and release of blood leukocytes, which protect the host against infection but also fuel inflammatory diseases. Objective: We aimed to develop imaging tools to explore vascular changes in the bone marrow niche during acute inflammation. Methods and Results: Using the TLR (Toll-like receptor) ligand lipopolysaccharide as a prototypical danger signal, we applied multiparametric, multimodality and multiscale imaging to characterize how the bone marrow vasculature adapts when hematopoiesis boosts leukocyte supply. In response to lipopolysaccharide, ex vivo flow cytometry and histology showed vascular changes to the bone marrow niche. Specifically, proliferating endothelial cells gave rise to new vasculature in the bone marrow during hypoxic conditions. We studied these vascular changes with complementary intravital microscopy and positron emission tomography/magnetic resonance imaging. Fluorescence and positron emission tomography integrin alpha V beta 3 imaging signal increased during lipopolysaccharide-induced vascular remodeling. Vascular leakiness, quantified by albumin-based in vivo microscopy and magnetic resonance imaging, rose when neutrophils departed and hematopoietic stem and progenitor cells proliferated more vigorously. Conclusions: Introducing a tool set to image bone marrow either with cellular resolution or noninvasively within the entire skeleton, this work sheds light on angiogenic responses that accompany emergency hematopoiesis. Understanding and monitoring bone marrow vasculature may provide a key to unlock therapeutic targets regulating systemic inflammation."

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For attribution in academic contexts, please cite this work as:

Vandoorne, K., Rohde, D., Kim, H. Y., Courties, G., Wojtkiewicz, G., Honold, L., Hoyer, F. F., Frodermann, V., Nayar, R., Herisson, F., Jung, Y., Desogere, P. A., Vinegoni, C., Caravan, P., Weissleder, R., Sosnovik, D. E., Lin, C. P., Swirski, F. K., & Nahrendorf^#, M. (2018). Imaging the Vascular Bone Marrow Niche During Inflammatory Stress. Circulation Research, 123(4), 415–427. https://doi.org/10.1161/circresaha.118.313302