Advancing Professionalization of Biobank Business Operations: Performance and Utilization.

Biobanks are now in the spotlight as key enablers supporting preclinical, clinical, and environmental research. Awareness of their value has increased along with the need for these infrastructures to be sustained through business-focused practices. Following our 2017 pilot survey on biobank business planning, we initiated a more comprehensive 38-question multiple-language worldwide survey on biobank sustainability. Two hundred seventy-six biobanks of various sizes and stages of business planning (in place, in progress or none) responded. About two-thirds were established in the last 10 years. Survey results confirm our hypothesis that biobanks with business plans or preparing such plans are trending toward more professional structures. Specific survey data focusing on performance metrics and utilization, as related to sustainability, are presented. Biobanks most frequently measured basic performance metrics (sample utilization, samples collected, samples distributed, internal projects supported). Metrics less often reported included sample and data quality, cost recovery, citations, and publications, typically correlating with higher levels of biobank complexity and professionalism. Biobanks reported supporting projects for both internal and external use, with support of projects within their own organizations as the main driver of biobanks, independent of business plan status. Having a business plan seemed to be a key factor for biobanks that had developed sustained support for external commercial projects. While under half of the biobanks reported both target and actual utilization rates, the responses provided valuable data on utilization. Target utilization rates were much higher (2.5 to 5 times higher) than the rate of actual use. Many of the biobanks report less than 10% utilization. Biobanks with low utilization rates make sustainability a very distant and likely unreachable goal. Our survey has provided some basic data about biobank business planning globally. Continued research should be done, with the data and information shared within the community for the good of all biobank stakeholders.

Advancing Professionalization of Biobank Business Operations: A Worldwide Survey.

Quality specimens from biobanks are key resources to support reproducible research. Sustaining biobanks requires robust management. We recently published a pilot survey that indicated that over half the participating biobanks had business plans in place and another third were working on business planning. While the results provided a clue to the status of business planning in biobanking, it was concluded that a longer and more in-depth survey and analysis were required. In April 2017, an extended survey was distributed worldwide in English, French, Chinese, German, and Spanish, through multiple channels. The survey was built using the Survey Monkey tool. Our hypothesis was that those biobanks that already have a business plan also have a more professional management structure. The questions were designed to understand more details about each biobank's business operations and communications. A total of 276 biobanks participated (China 65, France 40, United States 34, Spain 27, Germany 24, Australia 23, and rest of the world 63). About two thirds of the biobanks were established in the last 10 years. The responses provided data on the size of biobanks answering the survey, their status of business planning, and how and through what mediums they are communicating with customers. Biobanks with a business plan or preparing to have one showed a clear trend of having a customer strategy for marketing the samples and communicating with customers. No trend could be seen regarding websites and activities in social media. We confirmed our hypothesis that biobanks that have or are in the process of preparing a business plan are showing a trend toward more professional structures. In the biobanking community, the business mind-set and use of the business plan as a management tool have not quite arrived.

Considerations in establishing a post-mortem brain and tissue bank for the study of myalgic encephalomyelitis/chronic fatigue syndrome: a proposed protocol.

BACKGROUND: Our aim, having previously investigated through a qualitative study involving extensive discussions with experts and patients the issues involved in establishing and maintaining a disease specific brain and tissue bank for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), was to develop a protocol for a UK ME/CFS repository of high quality human tissue from well characterised subjects with ME/CFS and controls suitable for a broad range of research applications. This would involve a specific donor program coupled with rapid tissue collection and processing, supplemented by comprehensive prospectively collected clinical, laboratory and self-assessment data from cases and controls. FINDINGS: We reviewed the operations of existing tissue banks from published literature and from their internal protocols and standard operating procedures (SOPs). On this basis, we developed the protocol presented here, which was designed to meet high technical and ethical standards and legal requirements and was based on recommendations of the MRC UK Brain Banks Network. The facility would be most efficient and cost-effective if incorporated into an existing tissue bank. Tissue collection would be rapid and follow robust protocols to ensure preservation sufficient for a wide range of research uses. A central tissue bank would have resources both for wide-scale donor recruitment and rapid response to donor death for prompt harvesting and processing of tissue. CONCLUSION: An ME/CFS brain and tissue bank could be established using this protocol. Success would depend on careful consideration of logistic, technical, legal and ethical issues, continuous consultation with patients and the donor population, and a sustainable model of funding ideally involving research councils, health services, and patient charities. This initiative could revolutionise the understanding of this still poorly-understood disease and enhance development of diagnostic biomarkers and treatments.

Adenovirus-based targeting in myoblasts is hampered by nonhomologous vector integration.

Chromosomal correction of dystrophin gene mutations is a most desirable therapeutic solution for Duchenne muscular dystrophy, as it allows production of the full-length dystrophin under the control of locus-specific promoters. Here we explored gene targeting in conditionally immortal mouse dystrophin-deficient myoblasts. We constructed an adenoviral vector for the correction of the mdx mutation, containing 6.0 kb of sequence homologous to the target locus (partial intron 21 through to exon 24 with the normal sequence of exon 23) and a neomycin expression cassette inserted in intron 23. Adenovirus-based gene targeting was previously reported to be beneficial in mouse embryonic stem cells, resulting in one targeted integration per three integration events. However, we found no targeted integration events among 144 stably transduced G418-resistant myoblast clones, reflecting efficient random integration of the adenoviral vector in myogenic cells. We found that mouse myoblasts are capable of integrating recombinant adenoviral DNA with an efficiency approaching 1%. Interestingly, dermal fibroblasts integrate adenoviral DNA up to 100 times less efficiently than myoblasts from the same mice. We also show that the efficiency of recombinant adenoviral DNA integration is influenced by preinfection cell density, possibly indicating the importance of cellular DNA replication for adenoviral integration.

Lack of galectin-1 results in defects in myoblast fusion and muscle regeneration.

Galectin-1 has been implicated in the development of skeletal muscle, being maximally expressed at the time of myofiber formation. Furthermore, in the presence of exogenous galectin-1, mononuclear myoblasts show increased fusion in vitro. In the current study, we have used the galectin-1 null mouse to elucidate the role of galectin-1 in skeletal muscle development and regeneration. Myoblasts derived from the galectin-1 mutant showed a reduced ability to fuse in vitro. In galectin-1 null mutants, there was evidence of a delay in muscle fiber development at the neonatal stage and muscle fiber diameter was reduced when compared with wild-type at the adult stage. Muscle regeneration was also compromised in the galectin-1 mutant with the process being delayed and a reduced fiber size being maintained. These results, therefore, show a definitive role for galectin-1 in fusion of myoblasts both in vitro, in vivo, and in regeneration after recovery from induced injury.

Muscle stem cells.

Since its discovery four decades ago, the satellite cell of skeletal muscle has been implicated as the major source of myogenic cells involved in growth and repair of muscle fibres. This review not only looks at the role of the satellite cell in these processes but discusses how cells derived from other sources and tissues have recently been implicated in muscle formation and regeneration. Muscle itself also yields cells that contribute to other cell lineages although it is currently debated as to whether these cells originate within muscle or have migrated there from other tissues. The reality of using cells from muscle or other tissues to repair diseased muscle fibres is also addressed.

The effect of galectin-1 on the differentiation of fibroblasts and myoblasts in vitro.

Normal murine dermal fibroblasts implanted into the muscles of the mdx mouse, a model for Duchenne muscular dystrophy, not only participate in new myofibre formation but also direct the expression of the protein dystrophin which is deficient in these mice. We have reported that the lectin galectin-1 is implicated in the conversion of dermal fibroblasts to muscle. In the current work we confirm the presence of galectin-1 in the medium used for conversion. Furthermore we report that exposure of clones of dermal fibroblasts to this lectin results in 100% conversion of the cells. Conversion was assessed by the expression within the cells of the muscle-specific cytoskeletal protein desmin. We also investigate the effects of galectin-1 on cells of the C2C12 mouse myogenic cell line and on primary mouse myoblasts. Exposing both transformed and primary myoblasts to the lectin resulted in an increase in fusion of cells to the terminally differentiated state in both types of cultures. Galectin-1 does not cause the myogenic conversion of murine muscle-derived fibroblasts.

The involvement of galectin-1 in skeletal muscle determination, differentiation and regeneration.

The dogma that a cell is rigidly committed to one tissue type has been heavily challenged over the past few years with numerous reports of transdifferentiation of cells between different lineages. Cells capable of entering lineages other than that of their tissue of origin have been identified in several diverse tissues. Recently we have focussed on a non-committed myogenic cell within the dermis that is capable, under certain conditions, of expressing muscle specific markers and even fusing to the terminally differentiated stage of muscle cell development. We have identified galectin-1 as being a potent factor implicated in this process. In this review we discuss our findings and consider the involvement of galectin-1 in muscle determination, differentiation and regeneration.