A group of seasoned experts from the International Society for Biological and Environmental Repositories explain the notion of employing “living biobanks” to advance the field of biomedical research
Technological advancements over the recent decades have enabled the long-term storage of high-quality biological material at very low temperatures. We can now store biological material for a great length of time in biobanks: where biological samples (bodily fluid or tissue) and associated data are collected, annotated, transferred, stored and redistributed for future research in order to improve our understanding of health and disease. The process which enables the preservation of structurally intact living cells and tissues is called “cryopreservation.” More specifically, during cryopreservation, biological materials are cooled to cryogenic temperatures, commonly to -196 °C/-321 °F the temperature of liquid nitrogen. At these low temperatures, biological activity slows considerably, effectively halting the biochemical reactions that lead to cell death and DNA degradation and allowing for near indefinite storage of the samples.
Recent scientific advances in cryopreservation have enabled the prospect of establishing “living biobanks” that store viable, functional tissue or replicable cell types for years to decades. This could have a significant impact across basic biological research, medicine and the biopharma industry; however, the effects of such applications are underexplored. For example, banking and long-term storage of stem cells or stem-like cells in different stem cell platforms represent a fundamental resource, preserving the original features of stem cells for patient-specific clinical applications. (1)
The International Society for Biological and Environmental Repositories (ISBER) recently held a roundtable discussion at the 2018 annual meeting on this concept, building on a National Science Foundation (NSF, U.S.)- funded technology road mapping process, the recent “Organ Banking Summits” held at Harvard and Stanford Universities, and roundtable discussions were held at the White House and on Capitol Hill during the last several years. Further demonstrating the application and promise of these technologies, the National Cancer Institute (NCI) recently launched a new project entitled “The Human Cancer Models Initiative (HCMI)” which is a collaborative international consortium that is generating novel, next-generation, tumour-derived culture models (living biobanks) annotated with genomic and clinical data.
The “Apollo Program” of living biobanks
The above meetings focused on developing a mini- “Apollo Program” in cryopreservation to lengthen the shelf-life of living tissues and whole organs. Early proofs of concept for such research advances include the banking of whole sheep ovaries (resulting in live births), human digits, human cartilage, and a rabbit kidney at deep cryogenic temperatures and storage of organs such as rat hearts and rat livers at high subzero temperatures. The U.S. government is currently funding dozens of labs to develop cryopreservation methods for living tissues. This concept has received significant support from diverse stakeholder organisations such as (i) the International Society for Cryobiology, which has co-organised several meetings and sessions on the concept, and the (ii) American Society of Transplantation, which launched a new branch of its organisation focused on this concept. A number of organisations were signatories to a consensus article in Nature Biotechnology outlining the vast potential of these advances to change the landscape of medicine and biomedical research. (2)
Researchers agree that many biobank tissues represent “low hanging fruit” in this effort, as the technical hurdles are much lower for collections of cells or simple tissues than for larger vascularized tissues or whole organs. There are a great number of tissues (or cells) and/or biologics that could soon be stored in “living biobanks”. These can include solid tumour biopsies, organ and brain slices, resected brain tissue, cadaveric donor skin, cadaveric bone marrow, reproductive organs and tissues, pancreatic islets, a variety of neonatal tissues, and blood vessels. (3)
The awaiting scientific discoveries are only one of the essential steps towards a great many potential applications. Techniques currently developed within the context of living biobanks and cryopreservation of living tissue can be applied in preclinical testing, designing disease models, biomarker discovery, toxicity (safety) evaluation of pharmaceutical agents, greatly improved tissue quality for immunohistochemistry (IHC) leading, for example, to precision medicine approaches in the diagnoses and treatments of cancer types. (4)
This same concept is already being applied to cell lines such as tumour and primary epithelial cells, for example, patient-derived xenograft models, organoids, conditionally reprogrammed cells, induced pluripotent cells, and other cancer precision medicine applications, these represent an unexhausted resource of living biobanks. However, these concepts are applied in very many different ways by the academic and private sectors, representing an actively growing field that has yet to reach clinical consensus or maturity. ISBER is launching a special interest group to explore these and other applications. This group will unite stakeholders in these diverse areas, who will aim to provide (hopefully universal) recommendations to guide the development of new biobanking technologies and ultimately the establishment of the first living biobanks.
Even without further advances in cryopreservation technology, the existing technological opportunities today can greatly expand the number and applications of living biobanks. However, key challenges need to be overcome in order to capitalise on these opportunities, including a clearer articulation of both the scientific and clinical impact, as well as of the prioritisation of funding and regulatory actions required to allow this emerging field to reach its full potential.
1 Lisanti MP and Tanowitz HB. (2012) Translational Discoveries, Personalized Medicine, and Living Biobanks of the Future. Am J Pathol; 180(4): 1334–1336.
2 Giwa S, Lewis JK, Alvarez L, et al. (2017) The promise of organ and tissue preservation to transform medicine. Nat Biotechnol; 35(6): 530- 542. doi: 10.1038/nbt.3889.
3 Agarwal S and Rimm DL (2012) Making every cell like HeLa: a giant step for cell culture. Am J Pathol; 180: 443–445.
4 van de Wetering M, Francies HE, Francis JM, et al. (2015) Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell;161(4):933-45. doi: 10.1016/j.cell.2015.03.053.
Kate M. Franz
Organ Preservation Alliance, Berkeley, California, U.S.
Center for Cell Reprogramming, Lombardi Comprehensive Cancer Center, Georgetown University, Washington D.C., U.S.
International Agency for Research on Cancer, World Health Organization (WHO), Lyon, France
Jedediah K. Lewis
Organ Preservation Alliance, Berkeley, California, U.S.
International Society for Biological and Environmental Repositories
Tel: +1 604 484 5693