Bone marrow niches (endosteal and perivascular) play important roles in both normal bone marrow function and pathological processes such as cancer cell dormancy. Unraveling the mechanisms underlying these events in humans has been severely limited by models that cannot dissect dynamic events at the niche level. Utilizing microfluidic and stem cell technologies, we present a 3D in vitro model of human bone marrow that contains both the perivascular and endosteal niches, complete with dynamic, perfusable vascular networks. We demonstrate that our model can replicate in vivo bone marrow function, including maintenance and differentiation of CD34 hematopoietic stem/progenitor cells, egress of neutrophils (CD66b), and niche-specific responses to doxorubicin and granulocyte-colony stimulating factor. Our platform provides opportunities to accelerate current understanding of human bone marrow function and drug response with high spatial and temporal resolution.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121245 | DOI Listing |
Blood Sci
January 2025
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, PUMC Department of Stem Cell and Regenerative Medicine, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Irradiation with X-rays has been widely utilized in the clinical treatment of solid tumors and certain hematopoietic malignancies. However, this method fails to completely distinguish between malignant and normal cells. Prolonged or repeated exposure to radiation, whether due to occupational hazards or therapeutical interventions, can cause damage to normal tissues, particularly impacting the hematopoietic system.
View Article and Find Full Text PDFOsteoarthr Cartil Open
March 2025
Pain Centre Versus Arthritis and Academic Unit of Injury, Recovery and Inflammation Sciences, University of Nottingham, UK.
Objectives: Histological osteochondral characteristics of inflammation, fibrosis, vascularity, cartilage islands, vessels entering cartilage, thickened trabeculae and cysts are associated with bone marrow lesions (BMLs) in human knee osteoarthritis (OA). We identified and developed a method for scoring comparable pathology in two rat OA knee pain models.
Methods: Rats (n = 8-10 per group) were injected with monoiodoacetate (MIA) or saline, or underwent meniscal transection (MNX) or sham surgery.
Bioact Mater
March 2025
Department of Orthopedics and Rehabilitation, USA.
Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair.
View Article and Find Full Text PDFMater Today Bio
December 2024
Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China.
The treatment of large bone defects remains challenging due to the lack of spatiotemporal management of the immune microenvironment, inflammation response and bone remodeling. To address these issues, we designed and developed a nanoparticle/hydrogel hybrid system that can achieve the combined and sequential delivery of an anti-inflammatory factor (IL-10) and osteogenic drug (icariin, ICA). A photopolymerizable composite hydrogel was prepared by combining gelatin methacryloyl (GelMA) and heparin-based acrylated hyaluronic acid (HA) hydrogels containing IL-10, and poly(dl-lactide-co-glycolide) (PLGA)-HA nanoparticles loaded with ICA were incorporated into the composite hydrogels.
View Article and Find Full Text PDFDiabet Med
December 2024
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter Medical School, Exeter, UK.
Aims: Acute hypoglycaemia promotes pro-inflammatory cytokine production, increasing the risk for cardiovascular events in diabetes. AMP-activated protein kinase (AMPK) is regulated by and influences the production of pro-inflammatory cytokines. We sought to examine the mechanistic role of AMPK in low glucose-induced changes in the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), which is elevated in people with diabetes.
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