Biobanks paving the way for personalised medicine

Written by Yan Jun Tan. Edited by Dr Chih Wei Teng

Introduction

The concept of biobanks may spark little excitement for most people. However the potential applications for regenerative medicine (RM), personalised medicine and oncology in the near future are anything but dull. Biobanks have the potential to advance personalised medicine and disease research where effective biomarker identification is vital.1 It parallels the Human Genome Project, which has advanced science through its application in microbiology, virology and pathology, leading to the development of novel technologies and analytical tools, including ChIP-Seq.2,3,4 For many research fields, biobanks will become a vital infrastructure and may expedite technologies such as 3D cell printing and potentially lead to a future of 3D organ printing.

What are biobanks?

Biobanking is the controlled storage of various types of organic material derived from different organisms. It acts as a repository of live cells where the entire phenome from their genome, transcriptome, proteome and metabolome can be studied and used for research, healthcare and clinical trials.5,6,7

Biobanks are currently used as a library of specimens ready for researchers to collect and use according to their needs. Biobanks reduce the time required by researchers to screen and collect samples from individuals and the administrative work that goes into the consenting process to gain access to samples. For example, researchers studying cancer can quickly gain a large variety of samples through the various cancer biobanks (Figure 1) established in Australia. to expedite research outcomes and conduct further studies of disease-gene associations.8,9 This is particularly useful for the research of monoclonal gammopathies7 and metastases.10

However, biobank technology is still very much in its early stage with much room to develop. For example, in the industry where biobanking services will be most valued, there has been a yearly increase in clinical trials of 15.5% (CAGR).11 The source materials for the allogeneic and autologous treatments in these trials could be derived from a biobank explicitly established for research, clinical trials and treatments. Like the human genome project, as scientific knowledge on cell differentiation, tissue engineering, and stem cells grows in parallel with biobank technologies and the regenerative medicine industry, newer technologies such as 3D cell and organ printing may become more feasible. This development would likely cause an increase in the demand for the genetic and phenotypic variation found in biobanks.

Additionally, combining biobanks with developing technologies such as organ on a chip and organoids presents many possibilities for research and clinical trials. Organ on a chip and or organoids allow for disease modelling drug testing to be conducted in vitro on human cell systems by mimicking in vitro conditions.12,13 This may expedite and decrease the costs of clinical trials, effectively reducing the gap between pre-clinical tests and human clinical trials.14,15 These systems can be derived from patient-derived healthy and tumour tissues.16 As these peripheral technologies develop, the use of biobanks would likely increase, given the range of samples ready and available for the required research purposes. Eventually, drug screening, efficacy and toxicity testing might be conducted in a microarray of generated organoids or organ on chip arrangements. This can help reduce risk to human patients in early phase clinical trials as the variations in drug efficacy and safety to phenotype can be screened early in vitro instead of on commonly used industry cell lines such as diploid fibroblast, HeLa cells or animal models.17,18

Figure 1: List of established Australian Biobanks (with approval to be listed) 19

Biobanking process

Figure 2: Flowchart for collecting, processing and banking samples for biobanks. 20

The general process for biobanking can be found in Figure 2, where samples are collected from patients with informed consent, followed by tissue processing and, in the case of blood, separation into their individual components for specific storage conditions. Blood samples have relatively high shelf lives as opposed to tissue and organ samples derived from patients. This is because they do not need to be stored in sub-zero temperatures before blood transfusions21, where there are many issues including reduced cell viability, damage incurred through crystallisation of liquids and cracking of tissues.

As the technologies in and surrounding biobanks improve, the shelf lives of banked samples are likely to be enhanced and enable many other tissue types to be banked with greater viable yields from samples. For example, although cord blood and cancer samples are the main forms of banked samples for their cell expansion capabilities and potential uses in therapies and research, this may expand to include tissue samples and whole organs. In turn, this may cause many new regenerative medicine therapies to become viable through the use of the samples in research and clinical practice. For example, banked organs may be used for implantation, lessening the burden on organ donations and potentially having better antigen matching for donor recipients. Alternatively, 3D printed organs in cellular scaffolds may become a viable therapeutic for those without significant antigen matching, using their banked cells or a suitable derived stem cell.

It is critical for informed consent to be gained due to ethical concerns surrounding the use of donated cells and derived cell lines and products. For biobanks, dynamic consent is the favoured model of consent. The increased use of blockchain technology could potentially be applied to this consent model for an immutable audit trail and individuals to provide dynamic consent.22

Centralised vs decentralised models of biobanking

If biobanks are so critical for advancement in medical research and clinical trials, it is imperative that the costs of biobanking and therefore, the use of specimens be reduced. There are a few operational models that are currently feasible, however each of them presents its own set of advantages and disadvantages. First, centralised models where all the specimens collected are stored in a single physical location allow for the most simple administrative model where inventory is easily tracked, organised and distributed. This will suit samples that can be kept for extended periods or samples with high self-renewal capability, such as cord blood and stem cells. However, this model results in the highest shipping and storage costs; separate storage for different products is required for GMP compliance e.g. chemo drugs.

However, with computing improvements alongside the advent and increased popularity of QR codes and increased database capabilities, quickly organising and tagging specimens in a less centralised model becomes more feasible and cost-effective.

Though decentralised models are more cost effective in theory as transportation costs are minimised23, this model will only be able to be applied cost-effectively for limited sample types. Processing and storage of specimens often require specialised equipment that sample collection sites may not have. A regional model may be the most cost-effective and reasonable model, where samples can be collected and shipped locally for tissue processing, preparation and storage. This will be particularly important with tissue and organ samples that cannot be stored as long as blood samples where red cells can be stored for up to 42 days at 2-6℃.21,23 With the current technology, organs can only be stored (and still transplanted) for a few days at best.24,25

The model type utilised will also likely be influenced by the banked samples and the final regenerative medicine therapy product in question. For example, stem cell therapies and 3D printed tissues and organs are likely to have a more centralised model due to the complexity of the process, seeding time and devices required for their manufacture. On the other hand, organ and blood samples will suit a more decentralised model where less specialised equipment may be necessary for their preservation.

Advancements necessary in the field

For the potential use of samples to be expanded and for tissues and organs to be able to be biobanked and utilised, several technological advancements are necessary. First, extend safe preservation times for all specimens; particularly tissues and organs. There remains a lack of consensus on optimal storage for donated organs; however, methods of extending organ and tissue viability over traditional static cold storage without freezing include: hypothermic machine perfusion and normothermic oxygenated perfusion, which artificially extend the viable storage duration by preventing progressive vacuolation of cytoplasm and preserve lysosomal integrity.26,27

Secondly the cryostasis and revival cocktails that: depress metabolic rate, minimise cryoinjury, enable vitrification and stabilise cellular structures need to be further optimised without using toxic chemicals.28,29

Development of new technologies such as nano warming show promise for increasing organ viability post-thawing, avoiding potential damage through non-uniform warming gradients which can cause cracking in organs. 30,31

This would cause a slew of benefits. Organs being able to be cryopreserved and used in transplantation could potentially reduce the burden on organ donation; reducing waiting times as repository organs can be stockpiled, resulting in better antigen matching for recipients. Additionally, with the extended storage times, biobanks can reduce obsolete inventory as samples can be kept for longer or undergo reduced cell death during freezing and thawing.

Conclusion

Biobanks will likely become an integral part of research and clinical trials in the future as parallel technologies in regenerative medicine therapies develop. Doing so may also unintentionally result in the standardisation of many laboratory processes, data acquisition, technical validation and sharing of biological and clinical data, encouraging collaboration between biotechnology companies as biobanking networks are established. Furthermore, regardless of the research direction, the base organic material required can be quickly and efficiently derived from biobanks for pre-clinical testing and biological therapies, becoming an invaluable infrastructure in medical research for large-scale analysis of biomarkers and efficacy.32 These features are essential for developing new treatments and will enable personalised medicine to be developed in a novel and more efficient manner.

References

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