Altered cellular dynamics and endosteal location of aged early hematopoietic progenitor cells revealed by time-lapse intravital imaging in long bones

Köhler, Annette G.; Schmithorst, Vince; Filippi, Marie–Dominique; Ryan, Marnie A.; Daria, Deidre; Gunzer, Matthias; Geiger, Hartmut

doi:10.1182/blood-2008-12-195644

Cited by 193 publications

(187 citation statements)

References 72 publications

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“…We next characterized the nature of aging‐associated changes in stroma (Köhler et al , 2009; Grassinger et al , 2010). Cells that are located < 10 cell diameters to the bone are enriched for stroma cells from the endosteal region of the bone referred to as the endosteal niche and were detached for our experiments by collagenase treatment (Fig 2Ai–iii).…”

Section: Resultsmentioning

confidence: 99%

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Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

et al. 2017

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Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age‐related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long‐term HSC frequency and loss of stem cell polarity. Exposure of aged HSCs to thrombin‐cleaved OPN attenuates aging of old HSCs, resulting in increased engraftment, decreased HSC frequency, increased stem cell polarity and a restored balance of lymphoid and myeloid cells in peripheral blood. Thus, our data suggest a critical role for reduced stroma‐derived OPN for HSC aging and identify thrombin‐cleaved OPN as a novel niche informed therapeutic approach for ameliorating HSC phenotypes associated with aging.

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Section: Resultsmentioning

confidence: 99%

“…Aged HSCs are found at a greater distance from the endosteum within the BM and present with a reduced lodging ability (Köhler et al , 2009). We next tested the contribution of loss of OPN to these aging‐associated phenotypes.…”

Section: Resultsmentioning

confidence: 99%

Osteopontin attenuates aging‐associated phenotypes of hematopoietic stem cells

et al. 2017

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“…Using this technique, trafficking of GFP-labeled preosteoclasts through the capillary walls could be markedly observed. 16 Grinding tibia cortex down to a 100 mm thickness permits to image the tibia marrow cavity 51 (Figure 2g-i).…”

Section: Vessel Wall Labelingmentioning

confidence: 99%

Assessment of bone vascularization and its role in bone remodeling

Lafage-Proust¹,

Roche²,

Langer³

et al. 2015

BoneKEy Reports

101

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Bone is a composite organ that fulfils several interconnected functions, which may conflict with each other in pathological conditions. Bone vascularization is at the interface between these functions. The roles of bone vascularization are better documented in bone development, growth and modeling than in bone remodeling. However, every bone remodeling unit is associated with a capillary in both cortical and trabecular envelopes. Here we summarize the most recent data on vessel involvement in bone remodeling, and we present the characteristics of bone vascularization. Finally, we describe the various techniques used for bone vessel imaging and quantitative assessment, including histology, immunohistochemistry, microtomography and intravital microscopy. Studying the role of vascularization in adult bone should provide benefits for the understanding and treatment of metabolic bone diseases.

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“…However, the calvaria bone marrow differs from that in long bones. Imaging within the long bone (tibia) has now been developed in the lab of Matthias Gunzer (Magdeburg, Germany) [3]. Using the novel approach, neutrophils, DC and macrophages have been shown to interact with marrow stroma.…”

Section: Preserving the Environment: Intravital Imaging By Two-photonmentioning

confidence: 99%