ORCID Profile
0000-0002-9579-9411
Current Organisation
University of Oxford
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Publisher: Proceedings of the National Academy of Sciences
Date: 05-01-2011
Abstract: With an aging population, skeletal fractures are increasing in incidence, including the typical closed and the less common open fractures in normal bone, as well as fragility fractures in patients with osteoporosis. For the older age group, there is an urgent unmet need to induce predictable bone formation as well as improve implant fixation in situations such as hip joint replacement. Using a murine model of slow-healing fractures, we have previously shown that coverage of the fracture with muscle accelerated fracture healing and increased union strength. Here, we show that cells from muscle harvested after 3 d of exposure to an adjacent fracture differentiate into osteoblasts and form bone nodules in vitro. The osteogenic potential of these cells exceeds that of adipose and skin-derived stromal cells and is equivalent to bone marrow stromal cells. Supernatants from human fractured tibial bone fragments promote osteogenesis and migration of muscle-derived stromal cells (MDSC) in vitro. The main factor responsible for this is TNF-α, which promotes first MDSC migration, then osteogenic differentiation at low concentrations. However, TNF-α is inhibitory at high concentrations. In our murine model, addition of TNF-α at 1 ng/mL at the fracture site accelerated healing. These data indicate that manipulating the local inflammatory environment to recruit, then differentiate adjacent MDSC, may be a simple yet effective way to enhance bone formation and accelerate fracture repair. Our findings are based on a combination of human specimens and an in vivo murine model and may, therefore, translate to clinical care.
Publisher: Georg Thieme Verlag KG
Date: 12-2012
Abstract: Bilateral extracranial-intracranial (EC-IC) bypass-grafting of the cerebral circulation is uncommon. We report a case of anterior cerebral artery EC-IC bypass using the thoracodorsal axis artery-graft. The bifurcation of the thoracodorsal axis allows bypass of both anterior hemispheres, while matching appropriate small-vessel dimensions.
Publisher: EMBO
Date: 14-03-2015
Abstract: The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low‐dose recombinant human TNF (rh TNF ) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rh TNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti‐ TNF impaired fracture healing. Addition of rh TNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL 2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR 2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rh TNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization.
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/BIO.049809
Abstract: Mechanical force is a fundamental regulator of cell phenotype. Myofibroblasts are central mediators of fibrosis, a major unmet clinical need characterized by the deposition of excessive matrix proteins. Traction forces of myofibroblasts play a key role in remodelling the matrix and modulates the activities of embedded stromal cells. Here, we employ a combination of unsupervised computational analysis, cytoskeletal profiling and single cell traction force microscopy as functional readout to uncover how the complex spatiotemporal dynamics and mechanics of living human myofibroblast shape sub-cellular profiling of traction forces in fibrosis. We resolve distinct biophysical communities of myofibroblasts, and our results provide a new paradigm for studying functional heterogeneity in human stromal cells.
Publisher: American Society for Clinical Investigation
Date: 08-2012
DOI: 10.1172/JCI62423
Publisher: Proceedings of the National Academy of Sciences
Date: 19-04-2018
Abstract: While stem cell therapy has become the standard of care for hematological disorders, challenges remain for the treatment of solid organ injuries. Targeting endogenous cells would overcome many hurdles associated with exogenous stem cell therapy. Alarmins are released upon tissue damage, and here we describe how upregulation of a physiological pathway by exogenous administration of a single dose of HMGB1, either locally or systemically, promotes tissue repair by targeting endogenous stem cells. We show that HMGB1 complexed with CXCL12 transitions stem cells that express CXCR4 from G 0 to G Alert . These primed cells rapidly respond to appropriate activating factors released upon injury. HMGB1 promotes healing even if administered 2 wk before injury, thereby expanding its translational benefit for erse clinical scenarios.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Jagdeep Nanchahal.