Microcirculation Research Group

Intravital images of various organs and tissues captured by the Microcirculation Research Group

Group leader: Dr Neena Kalia

Overview

Dysfunctional microcirculation is a hallmark of many diseases.  Our research focuses on using specialist intravital microscopy (IVM) to assess the central role the microcirculation plays in experimental models of injury.  We are able to directly image and quantitate a range of microvascular perturbations which include thromboinflammatory derangements as well as changes in tissue perfusion, functional capillary density and microvascular tone. 

Our research group

We specialise in real-time intravital imaging of microcirculatory disturbances that accompany ischaemia-reperfusion (I/R) injury. We have applied I/R injury to various vascular beds, including the gut, mesentery, kidney, liver and cremaster muscle, to understand site specific mechanisms governing microcirculatory perturbations.  We recently developed a novel method to intravitally image the impact of myocardial I/R injury on the coronary microcirculation in a beating heart environment.  We use this model to directly observe thromboinflammatory events within myocardial microvessels, particularly the trafficking, adhesion kinetics (rolling / adhesion / transmigration) and cross-talk between leukocytes and platelets with each other and vascular endothelium.  We are combining this method with laser speckle contrast imaging of the beating heart to quantitate overall organ perfusion and correlate these events with those taking place at the microvascular level. 

Using these powerful tools, we aim to identify novel cellular and molecular mechanisms contributing to coronary microcirculatory dysfunction that can be therapeutically manipulated for clinical benefit.  We are currently focused on the critical proinflammatory role of the IL-36/IL-36R pathway, a novel member of the IL-1 superfamily, in the heart.  Whether contemporary and novel cardiovascular drugs, such as anti-platelets, can be repurposed for treating coronary microcirculatory disturbances post-reperfusion injury is also being investigated.  We are also assessing the vasculoprotective benefits of adult bone marrow-derived stem cells in I/R injured organs, specifically, haematopoietic (HSC) and mesenchymal (MSC) stem cells.  We are developing strategies to enhance stem cell recruitment and their vasculoprotective efficacy using biochemical pre-treatment, 3D culture methods and microfluidic devices.  Determining whether cardiovascular co-morbidities such as ageing and diabetes increase the susceptibility of coronary microcirculation to I/R injury is a central component of the Dr Kalia’s programme of research.

Follow the research activities of the Microcirculation Research Group on Twitter @MRG_UoB

Key Resources

The University recently invested significantly in developing a world-class intravital microscopy facility at the Medical School through the award of a strategic equipment grant.  Dr Kalia is the Director this facility which is the first of its kind in the UK and leads the Imaging and Technology research theme for the Institute.  This facility is fully equipped with multiphoton and spinning disk confocal intravital microscopes, as well as laser Doppler and laser speckle imaging systems.  

The intravital imaging facility will consider collaborations from external parties on any aspects of vascular research - please contact Dr Kalia for further information.

Imaging microvessels in their natural habitat

  • Cell-cell interactions
  • Real-time thrombosis
  • Vascular integrityImaging microvessels in their natural habitat
  • Vascular permeability / leakage
  • Functional capillary density
  • Blood flow / perfusion
  • Blood (cell) / perfusion
  • Vessel diameter
  • Oxidative stress

Current Projects

  • Enhancing the vasculoprotective effects of stem cells (HSCs and MSCs) in IR injured organs
  • Identification of vasculoprotective stem cell sub-types
  • Role of the IL-36/IL-36R pathway in myocardial ischemia-reperfusion injury
  • Role of the IL-36/IL-36R pathway in liver disease
  • Impact of ageing on the coronary microcirculation
  • Impact of diabetes on the coronary microcirculation
  • Identifying anti-platelets drugs that are effective in IR injured coronary microcirculation

Recent Publications

Kavanagh DPJ, Kalia N.  Live intravital imaging of cellular trafficking in the cardiac microcirculation – beating the odds.  Frontiers Immunology 2019, 26;10:2782.

Du M, Kavanagh D, Zhang Z, Kalia N.  Designing microfluidic devices to sort haematopoietic stem cells based on their mechanical properties. Stem Cells International 2019, 2019:8540706.

Kavanagh DPJ, Lokman AB, Neag G, Colley A, Kalia N. Imaging the injured beating heart intravitally and the vasculoprotection afforded by haematopoietic stem cells.  Cardiovascular Research 2019, 115:1918-1932.

Du M, Kavanagh D, Kalia N, Zhang Z. Characterising the properties of haematopoietic and mesenchymal stem cells using     micromanipulation and atomic force microscopy. Med Eng Phys 2019, 73:18-29. 

 Kavanagh DPJ, Gallagher MT, Kalia N.  Tify: a predicted quality score-based frame rejection and registration tool for improving the output of unstable biomedical imaging. PLoS One 2019;14:e0213162

Hausenloy DJ, Barrabes JA, Bøtker HE, Davidson SM, Di Lisa F, Downey J, Engstrom T, Ferdinandy P, Carbrera-Fuentes HA, Heusch G, Ibanez B, Iliodromitis EK, Inserte J, Jennings R, Kalia N, Kharbanda R, Lecour S, Marber M, Miura T, Ovize M, Perez-Pinzon MA, Piper HM, Przyklenk K, Schmidt MR, Redington A, Ruiz-Meana M, Vilahur G, Vinten-Johansen J, Yellon DM, Garcia-Dorado D.  Ischaemic conditioning and targeting reperfusion injury: a 30 year voyage of discovery.  Basic Res Cardiol. 2016, 111(6):70. Review.

Yemm A, Adams D, Kalia N. Targeting the delivery of systemically administered haematopoietic stem/progenitor cells to the inflamed colon using hydrogen peroxide and platelet microparticle pre-treatment strategies.  Stem Cell Res. 2015, 15(3):569-80

Kavanagh DP, Suresh S, Newsome PN, Frampton J, Kalia N. Pretreatment of mesenchymal stem cells manipulates their vasculoprotective potential while not altering their homing within the injured gut. Stem Cells. 2015, 33(9):2785-97. 

Kavanagh DP, Robinson J, Kalia N.  Mesenchymal stem cell priming: fine-tuning adhesion and function. Stem Cell Rev. 2014, 10(4):587-99. Review.

White RL, Nash G, Kavanagh DP, Savage CO, Kalia N. Modulating the adhesion of haematopoietic stem cells with chemokines to enhance their recruitment to the ischaemically injured murine kidney. PLoS One. 2013, 19;8(6):e66489. 

Staff

Principal Investigator

Dr Neena Kalia              

Postdoctoral Researchers

Dr Dean Kavanagh - Intravital Facility Manager
Joanne Mitchell

PhD Students

Kobkaew Bumroongthai
Juma El-Awaisi
Dylan Dabare