PBL – Fast-tracking innovations into healthcare, without the need for laboratory animals
Test your innovation in isolated organs and tissues maintained in perfect health outside of the body
We design bespoke models of injury that are comparable to the clinical setting
About Us
At Pebble we provide a globally unique service that accelerates the progress of your innovation to clinic using our novel ex-vivo living organ and tissue systems. We evaluate therapies, devices and biomedical materials in physiological environments where organ and tissue function is restored. Pathophysiological environments that closely mimic injury and disease can be induced, and monitored in real-time.
We offer a range of services from contract research through to technology partnerships, priding ourselves on a holistic approach to R&D support. We provide comprehensive packages which can be tailored to your needs.
We can support your research project from start to finish
We will produce study designs tailored specifically to your needs. We will design experiments based on advanced principles for preclinical trials, from simple proof of principle and proof of concept, to detailed end-stage analysis with power calculations, DoE (including advanced machine learning and AI approaches), N-dimensional analysis, latin hypercube and randomisation.
Total haemoglobin is recorded as a critical parameter of oxygen transport capacity. Oxyhaemoglobin is then determined, and the fraction is used to calculate oxygenation status (sO2). Carboxyhaemoglobin, (COHb), methaemoglobin, (MetHb) and deoxyhaemoglobin (HHb) provide additional information into oxygen transport status. The partial pressure of oxygen (pO2) and carbon dioxide (pCO2) reflect the level of oxygen delivery to the circuit. Total carbon dioxide (TCO2) is calculated based on the Henderson-Hasselbalch equation (using the Siggard-Andersen nonogram) and used as a marker of acid-base balance and disturbance. Finally, haematocrit is monitored from baseline, and loss of haematocrit is used as a marker of haemolysis. HCT, TcO2
As our perfusion circuits contain a complete circulating immune system, monitoring the immune and inflammatory response to a therapy or intervention is a critical parameter. We routinely quantify a range of key cytokines, complement factors, and immunoproteins in arterial and venous samples, as well as cell free mitochondrial and genomic DNA. We have a detailed flow cytometry panel to quantify a wide range of leukocytes, and includes functional markers to collectively generate a deep immunophenotypic profile.
We can perform next generation omics analyses of tissue samples and blood. This includes proteomic, metabolomic and transcriptomic mapping to give a broad expression signal within the tissue.
We routinely use thermal imaging to determine homogeneity of perfusion. We can prepare tissue samples for all microscopic approaches, and provide histology reports as needed.
Click on each of the circles below to find out more information about the services we offer!
PBL Packages
We can support your research project from start to finish
Reporting 6
Our senior scientific team can generate a written report with data interpretation.
Reporting 2
Our senior scientific team can generate a written report with data interpretation.
Reporting 1
Our senior scientific team can generate a written report with data interpretation.
Data
We have data analysts in the PBL team with a deep understanding of data handling and analysis.
Reporting 3
Our senior scientific team can generate a written report with data interpretation.
Grant writing
We can prepare work packages for grant applications, with background scientific rationale and objectives, detailed methodology and timescales.
Reporting 5
Our senior scientific team can generate a written report with data interpretation.
Experimental Design
We will produce study designs tailored specifically to your needs. We will design experiments based on advanced principles for preclinical trials, from simple proof of principle and proof of concept, to detailed end-stage analysis with power calculations, DoE (including advanced machine learning and AI approaches), N-dimensional analysis, latin hypercube and randomisation.
Reporting 8
Our senior scientific team can generate a written report with data interpretation.
Bespoke Protocol Development
We will build perfusion circuits to suit your requirements, with a wide range of tissue types and injury models available.
Reporting 7
Our senior scientific team can generate a written report with data interpretation.
Perfusion Protocol
The PBL team will perform perfusion experiments on your behalf. This is a highly complex procedure requiring a deep understanding of extracorporeal technology combined with organ anatomy and blood haemodynamics. With a collective experience of over 800 perfusions, we are ideally placed to run your perfusions to the highest standard.
Reporting 9
Our senior scientific team can generate a written report with data interpretation.
Statistics
We can perform all statistical analyses of data generated from a perfusion.
Interpretation
Our senior scientific team can provide detailed interpretation of data.
Presentation
We can generate graphical representations of all data and produce presentation ready slides.
Written Report
Our senior scientific team can generate a written report with data interpretation.
Biomarkers
We collect blood perfusate and tissue biopsies frequently throughout an experiment. We also collect urine and bile where a kidney and/or liver is included on the circuit. We can then perform detailed sample analysis to evaluate existing biomarkers, or to identify potential new biomarkers of health or injury.
Organ Function
The function of the organ (or multiple organs/tissues) is performed as a standard perfusion parameter. We utilise existing technology used in clinical practice to do this, so any data is directly comparable to clinic.
Haemodynamics
Haemodynamic monitoring is a key parameter of perfusion. We use mean arterial pressure and flow, and intra-tissue vascular resistance as markers of organ/tissue haemodynamics. Changes to pressure of flow following the introduction of a therapy or intervention can be used to evaluate safety.
Metabolism
We quantify glucose, lactate and bicarbonate, and calculate consumption throughout perfusion (specific to each perfused organ and tissue via arterial and venous blood gas). We also record base deficit/excess and blood pH. Electrolytes including K+, Cl-, Na+ and Ca++ are monitored and used to calculate anion gap (with/out potassium correction).
CO-Oximetry
Total haemoglobin is recorded as a critical parameter of oxygen transport capacity. Oxyhaemoglobin is then determined, and the fraction is used to calculate oxygenation status (sO2). Carboxyhaemoglobin, (COHb), methaemoglobin, (MetHb) and deoxyhaemoglobin (HHb) provide additional information into oxygen transport status. The partial pressure of oxygen (pO2) and carbon dioxide (pCO2) reflect the level of oxygen delivery to the circuit. Total carbon dioxide (TCO2) is calculated based on the Henderson-Hasselbalch equation (using the Siggard-Andersen nonogram) and used as a marker of acid-base balance and disturbance. Finally, haematocrit is monitored from baseline, and loss of haematocrit is used as a marker of haemolysis. HCT, TcO2
Immune Profiling
As our perfusion circuits contain a complete circulating immune system, monitoring the immune and inflammatory response to a therapy or intervention is a critical parameter. We routinely quantify a range of key cytokines, complement factors, and immunoproteins in arterial and venous samples, as well as cell free mitochondrial and genomic DNA. We have a detailed flow cytometry panel to quantify a wide range of leukocytes, and includes functional markers to collectively generate a deep immunophenotypic profile.
Omics Approaches
We can perform next generation omics analyses of tissue samples and blood. This includes proteomic, metabolomic and transcriptomic mapping to give a broad expression signal within the tissue.
Imaging
We routinely use thermal imaging to determine homogeneity of perfusion. We can prepare tissue samples for all microscopic approaches, and provide histology reports as needed.
Reporting 10
Our senior scientific team can generate a written report with data interpretation.
Reporting 11
Our senior scientific team can generate a written report with data interpretation.
Reporting 12
Our senior scientific team can generate a written report with data interpretation.
Immune Profiling
As our perfusion circuits contain a complete circulating immune system, monitoring the immune and inflammatory response to a therapy or intervention is a critical parameter. We routinely quantify a range of key cytokines, complement factors, and immunoproteins in arterial and venous samples, as well as cell free mitochondrial and genomic DNA. We have a detailed flow cytometry panel to quantify a wide range of leukocytes, and includes functional markers to collectively generate a deep immunophenotypic profile.
No laboratory animals
We do not use laboratory animals, which is a unique offering from Pebble. Instead we work with farms to develop the highest standards of animal husbandry, with unlimited outdoor access, antibiotic free approaches, and social group housing. We only use organs and tissues that are surplus to the food industry. This means no animal licences or regulatory approvals are required.
We think this is the right ethical approach, as it replaces the laboratory pig while still providing a superior model compared to in-vitro and rodents. It also de-risks the innovation development pathway, as a serious adverse event causes no harm, and does not need to be reported to the home office. As a result, failure is an acceptable part of the R&D process, and identifying the cause of failure is rapidly accelerated.
The cost of ex-vivo living systems is also significantly less than in-vivo porcine experiments, by as much as 90%, so investigating concept therapies and moving to high-throughput is realistic and achievable.
No laboratory animals
We do not use laboratory animals, which is a unique offering from PBL. Instead we work with farms to develop the highest standards of animal husbandry, with unlimited outdoor access, antibiotic free approaches, and social group housing. We only use organs and tissues that are surplus to the food industry. This means no animal licences or regulatory approvals are required.
We think this is the right ethical approach, as it replaces the laboratory pig while still providing a superior model compared to in-vitro and rodents. It also de-risks the innovation development pathway, as a serious adverse event causes no harm, and does not need to be reported to the home office. As a result, failure is an acceptable part of the R&D process, and identifying the cause of failure is rapidly accelerated.
The cost of ex-vivo perfusion is also significantly less than in-vivo porcine experiments, by as much as 90%, so investigating concept therapies and moving to high-throughput is realistic and achievable.
If you would like to learn more about how we can help, please get in touch here
