BioBlood is funded by the European Research Council,
ERC Grant n. 340719.
The overall aim of BioBlood is the development of an integrated experimental (in vitro)/modelling (in silico) platform that will deliver personalised healthcare clinical products in cellular therapy (production of RBC product for transfusion) and drug therapy (optimal treatment regime for AML and CLL). BioBlood will achieve the overall aim by addressing 3 research challenges and delivering on the corresponding objectives:
1) Technical Challenge
BioBlood platform will be achieved through delivery of the technical components:
a) Objective 1: Development and application-specific adaptation of the in vitro system (3D perfusion hollow fibre bioreactor);
b) Objective 2: Development and application-specific adaptation of the in silico system (growth kinetic, cell cycle, pharmacokinetic & pharmacodynamics model).
2) Implementation Challenge
The BioBlood platform will receive the patient/disease-specific input of cells/tissue and data to produce:
c) Objective 3: Functional red blood cell product;
d) Objective 4: Predictive AML & CLL disease/treatment model that is validated through the in vitro system.
3) Pre-Clinical Challenge
Through collaboration with partners in the National Blood Service (Prof David Anstee and Drs Ash Toye, Rebecca Cardigan and Fiona Regan) and Celgene (Dr John Lynes), BioBlood will deliver personalised healthcare in cellular and drug therapy:
e) Objective 5: Production of clinically relevant red blood cells in a cost-effective manner for transfusion;
f) Objective 6: Validated and optimised patient- & disease-specific chemotherapy treatment protocol.
The novelty of BioBlood resides with the technical advances in the in vitro and in silico components and is outlined below:
In Vitro Platform
i. Cytokine-free culture of primary haematopoietic cells;
ii. Long-term culture (over 2 months with high viability);
iii. Recapitulation of haematopoietic-inductive microenvironment (“niche-like” structures) through the provision of application-tailored scaffold;
iv. Maintenance of progenitor clonogenic capacity;
v. Continuous harvesting of cells by a process that simulates crossing of mature cells through the endothelial wall;
vi. Perfusion of nutrients and removal of metabolites (in a cost-effective manner) through the bio-inspired hollow fibres;
vii. Production of oxygen-carrying, enucleated red blood cells;
viii. Maintenance of leukaemic blasts (cytokine-free);
ix. Experimental delivery of chemotherapy agent(s)
In Silico Platform
i. An integrated growth kinetic, cell death, cell cycle, pharmacokinetic and pharmacodynamics model;
ii. An integrated model development, analysis, and validation platform;
iii. Experimentally-derived patient- and disease specific data (such as growth kinetics, cell death and cell cycle);
iv. Novel model-predictive control and optimisation of chemotherapy treatment regime through the collaboration with Prof Stratos Pistikopoulos (Texas A&M).