Aims: Neovascularization is an important element of long-term functional recovery during chronic ischaemia. We postulated that haeme oxygenase (HO) is required for progenitor cell recruitment, neovascularization, and blood flow recovery after critical hindlimb ischaemia (HLI).
Methods And Results: The femoral artery was ligated in FVB/N mice proximal to its superficial and deep branches. Blood flow in the ischaemic hindlimb was determined by laser Doppler perfusion imaging. Capillary density was measured by isolectin staining, and mobilization of Sca-1(+)/Kdr(+) progenitor cells by FACS analysis. Progenitor cell recruitment to the ischaemic hindlimb was assessed after Tie2-lacZ transgenic bone marrow transplantation. Blood flow recovery after femoral artery ligation was significantly blunted in mice treated with the HO inhibitor tin protoporphyrin-IX (25 mg/kg i.p., every other day). HO-inhibited mice developed more pronounced limb necrosis, associated with impaired hindlimb motor function. Capillary density in the ischaemic hindlimb and mobilization of Sca-1(+)/Kdr(+) progenitor cells were significantly reduced after HO inhibition. After transplantation of Tie2-lacZ transgenic bone marrow cells into lethally irradiated wild-type mice, fewer LacZ(+) cells were detected in the ischaemic hindlimb muscle of HO-inhibited mice. Mechanistically, HO inhibition prevented the establishment of a stromal cell-derived factor-1 gradient for progenitor cell mobilization between the ischaemic hindlimb and bone marrow.
Conclusion: HOs are required for progenitor cell recruitment, neovascularization, and functional recovery after HLI.
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http://dx.doi.org/10.1093/cvr/cvm107 | DOI Listing |
Discov Oncol
January 2025
Department of General Surgery, The Second Affiliated Hospital of the Air Force Medical University, Xi'an, 710038, China.
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November 2024
Institute of Immunology and Immunotherapy, College of Medicine and Health, University of Birmingham, Birmingham, UK. Electronic address:
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January 2025
Institute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Chondrocyte senescence is an important pathogenic factor causing osteoarthritis (OA) progression through persistently producing pro-inflammatory factors. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) have shown anti-inflammatory effects in OA models, while persistent existence of senescent chondrocytes still promotes cartilage destruction. Therefore, improving the targeted elimination ability on senescent chondrocytes is required to facilitate the translation of MSC-sEVs in OA treatment.
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Corneoplastic Unit and Eye Bank, Queen Victoria Hospital NHS Foundation Trust, East Grinstead, UK.
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Sci Rep
January 2025
Foot and Ankle Research and Innovation Lab (FARIL), Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Tendon injuries present significant medical, social, and economic challenges globally. Despite advancements in tendon injury repair techniques, outcomes remain suboptimal due to inferior tissue quality and functionality. Tissue engineering offers a promising avenue for tendon regeneration, with biocompatible scaffolds playing a crucial role.
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