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Peer-reviewedCC BYBone Research

From complexity to clarity: aging bone marrow niche in bone and blood regeneration and malignancy

  • Nainita Roy1,2
  • Hanyu Liu2
  • Allison L Horenberg3,4
  • Arvind P. Pathak3,5,6,4
  • Junyu Chen7,2
  • Saravana Kumar Ramasamy8,9
  • Martine Esther Cohen-Solal10,11
  • Aline Bözec12,13
  • Warren L. Grayson3,14,15,5,4
  • Anjali P. Kusumbe16,17
17 affiliations
  1. 1Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA
  2. 2Tissue and Tumor Microenvironments Lab, Cancer Discovery and Regenerative Medicine Program, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  3. 3Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  4. 4Translational Therapeutics & Regenerative Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  5. 5Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA
  6. 6Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  7. 7State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
  8. 8Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  9. 9Multidisciplinary Institute of Ageing (MIA-Portugal), University of Coimbra, Coimbra, Portugal
  10. 10Department of Rheumatology and Reference Center for Rare Bone Diseases, Hospital Lariboisière, Paris, France
  11. 11Inserm U1132 Bioscar, Université Paris Cité, Centre Viggo Petersen Hôpital Lariboisière, APHP.Nord, Paris, France
  12. 12Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany
  13. 13Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany
  14. 14Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA
  15. 15Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, USA
  16. 16Multidisciplinary Institute of Ageing (MIA-Portugal), University of Coimbra, Coimbra, Portugal. [email protected]
  17. 17Tissue and Tumor Microenvironments Lab, Cancer Discovery and Regenerative Medicine Program, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. [email protected]
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Abstract

The bone marrow niche (BMN) plays a central role in regulating hematopoietic stem-cell (HSC) maintenance, lineage commitment, and immune homeostasis, while also supporting osteogenesis and maintaining skeletal integrity. Once considered static, the BMN is now recognized as a dynamic and responsive microenvironment that integrates local signals and systemic cues to meet physiological demands and respond to stress. Aging causes profound and progressive changes to this niche, leading to functional decline across both hematopoietic and stromal compartments. Recent advances in high-resolution imaging, single-cell and spatial transcriptomics, and in vivo lineage tracing have revealed remarkable heterogeneity and plasticity within the vascular and mesenchymal elements of this niche. Yet, key questions remain unresolved, including the identity and hierarchy of mesenchymal and osteolineage cells, the specialization of subsets of endothelial cells, the integration of systemic regulation, and whether the aging bone marrow acts as a driver or a passenger in malignancy and chronic inflammation. This review revisits current models of the BMN, with a focus on the reciprocal interactions between osteogenic cells and specialized vasculature, and how their disruption during aging impairs hematopoietic output and skeletal remodeling. We also examine how systemic factors such as neural input, metabolic status, and inflammatory signaling influence the aging of the BMN. Finally, we highlight emerging translational platforms, including iPSC-derived bone marrow organoids, engineered niches/hydrogels, and vascularized organ-on-chip systems, that enable mechanistic testing of rejuvenation strategies. Together, these insights have the potential to pave the way toward targeted interventions that restore the function of the BMN and promote healthy aging of the bone and blood systems.

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Cite

BibTeXRIS
BibTeX
@article{roy2026from,
  title = {{From complexity to clarity: aging bone marrow niche in bone and blood regeneration and malignancy}},
  author = {Nainita Roy and Hanyu Liu and Allison L Horenberg and Arvind P. Pathak and Junyu Chen and Saravana Kumar Ramasamy and Martine Esther Cohen-Solal and Aline Bözec and Warren L. Grayson and Anjali P. Kusumbe},
  journal = {Bone Research},
  year = {2026},
  month = may,
  doi = {10.1038/s41413-026-00543-3},
  url = {https://doi.org/10.1038/s41413-026-00543-3},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - From complexity to clarity: aging bone marrow niche in bone and blood regeneration and malignancy
AU  - Nainita Roy
AU  - Hanyu Liu
AU  - Allison L Horenberg
AU  - Arvind P. Pathak
AU  - Junyu Chen
AU  - Saravana Kumar Ramasamy
AU  - Martine Esther Cohen-Solal
AU  - Aline Bözec
AU  - Warren L. Grayson
AU  - Anjali P. Kusumbe
PY  - 2026
DA  - 2026/05/18
JO  - Bone Research
DO  - 10.1038/s41413-026-00543-3
UR  - https://doi.org/10.1038/s41413-026-00543-3
AB  - The bone marrow niche (BMN) plays a central role in regulating hematopoietic stem-cell (HSC) maintenance, lineage commitment, and immune homeostasis, while also supporting osteogenesis and maintaining skeletal integrity. Once considered static, the BMN is now recognized as a dynamic and responsive microenvironment that integrates local signals and systemic cues to meet physiological demands and respond to stress. Aging causes profound and progressive changes to this niche, leading to functional decline across both hematopoietic and stromal compartments. Recent advances in high-resolution imaging, single-cell and spatial transcriptomics, and in vivo lineage tracing have revealed remarkable heterogeneity and plasticity within the vascular and mesenchymal elements of this niche. Yet, key questions remain unresolved, including the identity and hierarchy of mesenchymal and osteolineage cells, the specialization of subsets of endothelial cells, the integration of systemic regulation, and whether the aging bone marrow acts as a driver or a passenger in malignancy and chronic inflammation. This review revisits current models of the BMN, with a focus on the reciprocal interactions between osteogenic cells and specialized vasculature, and how their disruption during aging impairs hematopoietic output and skeletal remodeling. We also examine how systemic factors such as neural input, metabolic status, and inflammatory signaling influence the aging of the BMN. Finally, we highlight emerging translational platforms, including iPSC-derived bone marrow organoids, engineered niches/hydrogels, and vascularized organ-on-chip systems, that enable mechanistic testing of rejuvenation strategies. Together, these insights have the potential to pave the way toward targeted interventions that restore the function of the BMN and promote healthy aging of the bone and blood systems.
SN  - 2095-4700
SN  - 2095-6231
ER  -