What we offer
The Pebble team has extensive experience in organ and tissue perfusion. We have developed models of the kidney, liver, heart, lung, limb (with skin, muscle, bone, nerve), pancreas, eye, and blood (the circulating immune compartment, RBCs, platelets).
What are Living Systems?
A Living System involves removing organs and tissues from the body and attaching them to a circuit which mimics the in-vivo setting. The blood vessels of the tissues are perfused with blood-based solutions at physiological pressures and flow using state-of-the-art levitating centrifugal pumps. Oxygenation and carbon dioxide clearance are performed by the addition of an oxygenator, and a heater maintains normothermia (normal body temperature). For prolonged perfusion, nutritional support is infused. As a result of our highly complex circuits and protocols, organ function and metabolism is preserved. In each of our models, kidneys urinate, livers secrete enzymes, both biochemically recycle metabolic toxins, lungs breathe, hearts beat, the muscles, fascia, and skin of a limb physiologically metabolise glucose and lactate. The circulating immune system corresponds closely with in-vivo, responding to stimuli such as LPS and infectious organisms.
Using these models we can test any intervention and induce a wide range of injuries, while monitoring parameters that are comparable to the patient. This includes deep haemodynamic and biomarker profiling as well as detailed functional assessment (i.e. gaseous exchange of the lung, ejection fraction of a beating heart, kidney creatinine clearance), all in real time.
What we offer
We can bespoke build complex living systems with the simultaneous perfusion of multiple organs, tailored to your needs. This can include models of acute injury (i.e. crush, penetrating trauma, burns, barometric), metabolic derangement (i.e. acidosis, base deficits, glucose/insulin), cytokine release syndrome, toxicity etc. As perfusion enthusiasts, we’re happy to push the boundaries – so if you have a model in mind, no matter how complex, get in touch.
A Living Kidney System provides a physiological environment where kidney function and metabolism is fully restored. Detailed biochemical profiling enables accurate assessment of lactate conversion to glucose (active neoglucogenesis), and bicarbonate recycling (monitored via blood bicarbonate, base deficit/excess, and blood pH). Real-time monitoring or haemodynamics enables the rapid identification of vascular changes, from mean arterial pressures and flow to intrarenal vascular resistance. The ureter of the kidney is cannulated, and urine production is isolated from the circuit. This provides the unique opportunity to fully evaluate renal function via real-time blood and urinalysis. The blood can be bolused with creatinine, allowing estimated glomerular filtration rate (GFR) to be calculated via creatinine clearance.
The fractional extraction of sodium excretion, along with urinary output also provides indications of functionality. Additionally, urinary biomarkers of kidney injury such as neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 can be assessed. The impact of any therapeutic intervention can therefore be determined, with the clear advantage of having a paired control.
Pebble’s Living Limb System
The liver is maintained in a metabolically active state, with physiological perfusion across the hepatic artery and portal vein. Bile is produced and collected via cannulation. A comprehensive panel of biomarkers are measured in real-time to give clinically relevant information on neoglucogenesis, bicarbonate recycling, base control, electrolyte balance, and co-oximetry. Drug interactions can be evaluated within the liver to analyse metabolic rate and decay or drug half-life. Bilirubin is used to monitor in real-time the stable state of the liver.
The Living Limb or Composite Flap System differs from other perfusion systems as it encompasses composite tissue. Muscle, nerve, skin and tendon functionality can be assessed via tensile strength, stimulation and capillary refill. This is therefore a unique model to evaluate trauma (such as burns, blunt force trauma and lacerations), controlled fractures, skin drug absorption and wound healing. The ability to perform paired analysis creates a realistic platform to assess treatment outcomes with a genetically identical control.
We have previously developed a two-chambered beating heart model based on the Langendorff system. Within this model, real-time monitoring of perfusion flow, left ventricular preload and afterload pressure, action potentials, cardiac output and volume loops is performed. This generates a complete profile of cardiac haemodynamics. Pacing studies can be performed, and cardiac arrest models are available including defibrillation to restore cardiac rhythm. As with all our models, detailed biochemical profiling of the blood is performed to monitor the impact of an innovation/intervention on blood biochemistry, metabolic profile, co-oximetry, and electrolyte balance.
Although currently not available in PBL, the scientific team have significant track-record in lung perfusion. If you are interested in lung perfusion please get in touch to discuss your needs.
Multi Organ Systems
Living Multi-organ Systems provides the opportunity to combine organs and tissues in a variety of combinations. This provides benefits over isolated organ perfusion as it allows for the interaction and communication between tissues to be assessed and monitored. The systemic interactions of therapeutics or interventions can therefore be assessed on a wider scale.
Circulating Immune System
We have developed a proprietary Living Blood System that can be used to determine the immunoreactivity/toxicity of an intervention in real-time. This is a critical tool as static leukocytes, RBCs and platelets behave fundamentally differently in-vitro than under physiological flow and pressure, with nutritional support and oxygen transport. In this system, detailed immunophenotyping, RBC functional analysis and platelet monitoring provides unique data that is unobtainable in-vitro. We are also part of a strategic alliance to access human blood using this approach.