The future therapeutic use of stem and mesenchymal derived cell types in personalised medicine indicates an essential need to be able to maintain the cells in a quiescent, differentiated state during storage and delivery to the patient to ensure potency is maintained. This delivery medium will need to be risk acceptable to regulatory authorities, therefore requiring the omission of animal derived serum or solvents (e.g., DMSO) currently used to cryopreserve the differentiated stem cells prior to patient administration.
Another aspect of preserving the integrity and functional viability of cells involves the utilisation of peripheral blood cell types (e.g., leucocytes, lymphocytes, T-cells) in the management of patient therapy. A formulation that provides an optimal fluid environment to maintain cellular integrity is paramount to validating diagnostic analysis to improvise a remedy. This requirement will be an essential feature in the quest to design a universal, artificial blood transfusion solution where stem cell derived red blood cells will obviate the current need for a patient to receive transfusions of a specific red cell type.
To satisfy the aforementioned requisites, AQIX® RS-I has been designed to be isosmotic, isotonic and isoioinic with human serum and interstitial fluid. It utilises a novel, acid-base (pH) buffering system designed to mimic the natural, α-stat pH mechanism of the imidazole groups in haemoglobin operating in mammals and human per se and, as such, provides an ideal fluid composition to retain the acid-base balance and integrity of human cells, e.g., lymphocytes, erythrocytes, hepatocytes, cardiomyocytes, both inside and outside the body.
In the conceptual design of AQIX® RS-I it was acknowledged that the natural, auto-regulatory processes observed in all cell types be addressed if AQIX® RS-I was to achieve a status as a universal perfusion and preservation solution for use with different human cells and tissues. The unique features of this formulation facilitate mitochondrial metabolism in the generation of the basic energy molecule, adenosine triphosphate (ATP), without which, all cells die. Unfortunately, red blood cells (RBC's) do not contain mitochondria to generate ATP, so the AQIX® RS-I contains the co-factor, thiamine pyrophosphate, which interacts with the RBC's enzyme, transketolase, to produce ATP resulting in increased longevity of these oxygen-haemoglobin carrying cells.
Audit trial data indicates that AQIX® RS-I satisfies the criteria necessary for use as a preservation storage and transportation fluid with the additional benefit that, unlike other commercial products, it is suitable for a myriad of stem cell and peripheral blood cell types without the addition of disruptive compounds (e.g., DMSO) for preservation of cell function under 'cold' (hypothermic) or body (normothermic) temperatures, the latter a requisite for use in cell culture bioreactors.
The benefits of adopting AQIX® RS-I technology can be summarised as:
- Manufactured to GMP standards
- AQIX® RS-I a shelf life to cover storage and delivery times of 12 – 120 hours
- Provides stable pH-buffering of pH 7.20 – 7.45 over 20 – 37 °C
- Offers reproducible Standard Operating Procedures
- Ability to 'hold' stem cells during storage and delivery in their differentiated format
- Operates under aerobic or anaerobic conditions to accommodate all stem cell types
- Suitable medium for use in cell culture containers currently used for transportation