A study published in Nature (2014) reports direct in vivo measurements of local oxygen concentration in the bone marrow (BM) of live mice using two-photon phosphorescence lifetime microscopy (2PLM). The research reveals that the BM has a low oxygen tension (pO₂), with values as low as 9.9 mmHg in deeper peri-sinusoidal regions. The endosteal region, which is less hypoxic, is perfused by small arteries often positive for the marker nestin. The study also shows that pO₂ values change dramatically after radiation and chemotherapy, indicating that stress can alter the stem cell metabolic microenvironment. The study highlights the complex oxygen distribution within the BM, with steep gradients forming hypoxic zones near blood vessels. The BM is densely perfused, including the endosteal region, raising questions about how such a highly vascularized tissue can support hematopoietic stem cells (HSCs) in a low oxygen environment. The research also identifies that HSCs reside in different niches, including vascular and endosteal regions, with distinct oxygen levels. Using a metalloporphyrin-based two-photon-enhanced phosphorescent probe, PtP-C343, the study enables non-contact pO₂ measurements through the intact skull with micrometer spatial resolution. The probe is protected by a dendrimer with a polyethylene glycol (PEG) overcoat to ensure biocompatibility and prevent unwanted interactions with biomacromolecules. The study confirms that the BM has a high vascular density and that pO₂ values in the BM are significantly lower than in the microvasculature of the brain, periosteum, and cortical bone. The study also shows that the pO₂ in the BM varies with distance from the endosteal surface, with the lowest values found in regions more than 40 µm from the bone. The research further demonstrates that the pO₂ in nestin+ vessels is significantly higher than in nestin- vessels, suggesting that these vessels have different metabolic environments. The study also examines the effects of cytoreductive therapy, such as radiation and chemotherapy, on BM pO₂. These treatments significantly elevate the overall BM pO₂, indicating that stress can alter the oxygen environment in the BM. The study also shows that HSPCs do not preferentially home to specific niches defined by low pO₂, suggesting that the oxygen environment is not the sole factor in HSC homing. The study concludes that the BM has a unique hypoxic landscape organized by its dense vascularity and high cellularity. The balance between oxygen supply and consumption can be altered by stress such as radiation and chemotherapy. The local topography is further defined by the positioning of different types of blood vessels within the BM. The study highlights the need to further examine the role of distinct vascular niches in HSC regulation.A study published in Nature (2014) reports direct in vivo measurements of local oxygen concentration in the bone marrow (BM) of live mice using two-photon phosphorescence lifetime microscopy (2PLM). The research reveals that the BM has a low oxygen tension (pO₂), with values as low as 9.9 mmHg in deeper peri-sinusoidal regions. The endosteal region, which is less hypoxic, is perfused by small arteries often positive for the marker nestin. The study also shows that pO₂ values change dramatically after radiation and chemotherapy, indicating that stress can alter the stem cell metabolic microenvironment. The study highlights the complex oxygen distribution within the BM, with steep gradients forming hypoxic zones near blood vessels. The BM is densely perfused, including the endosteal region, raising questions about how such a highly vascularized tissue can support hematopoietic stem cells (HSCs) in a low oxygen environment. The research also identifies that HSCs reside in different niches, including vascular and endosteal regions, with distinct oxygen levels. Using a metalloporphyrin-based two-photon-enhanced phosphorescent probe, PtP-C343, the study enables non-contact pO₂ measurements through the intact skull with micrometer spatial resolution. The probe is protected by a dendrimer with a polyethylene glycol (PEG) overcoat to ensure biocompatibility and prevent unwanted interactions with biomacromolecules. The study confirms that the BM has a high vascular density and that pO₂ values in the BM are significantly lower than in the microvasculature of the brain, periosteum, and cortical bone. The study also shows that the pO₂ in the BM varies with distance from the endosteal surface, with the lowest values found in regions more than 40 µm from the bone. The research further demonstrates that the pO₂ in nestin+ vessels is significantly higher than in nestin- vessels, suggesting that these vessels have different metabolic environments. The study also examines the effects of cytoreductive therapy, such as radiation and chemotherapy, on BM pO₂. These treatments significantly elevate the overall BM pO₂, indicating that stress can alter the oxygen environment in the BM. The study also shows that HSPCs do not preferentially home to specific niches defined by low pO₂, suggesting that the oxygen environment is not the sole factor in HSC homing. The study concludes that the BM has a unique hypoxic landscape organized by its dense vascularity and high cellularity. The balance between oxygen supply and consumption can be altered by stress such as radiation and chemotherapy. The local topography is further defined by the positioning of different types of blood vessels within the BM. The study highlights the need to further examine the role of distinct vascular niches in HSC regulation.