International Spinal Cord Injury Biobank: A Biorepository and Resource for Translational Research.

Over the past few decades, tremendous advances have been made in our understanding of the biological changes underpinning the devastating impairment of traumatic spinal cord injury (SCI). Much of this scientific research has focused on animal models of SCI, and comparatively little has been done in human SCI, largely because biospecimens from human SCI patients are not readily available. This paucity of scientific enquiry in human SCI represents an important void in the spectrum of translational research, as biological differences between animal models and the human condition need to be considered in the pre-clinical development of therapeutic approaches. The International Spinal Cord Injury Biobank (ISCIB) is a multi-user biorepository with the mission of accelerating therapeutic development in traumatic SCI through improved biological understanding of human injury, and the vision of serving as a global research resource where human SCI biospecimens are shared with researchers around the world. Aligned with internationally recognized best practices, ISCIB's formal governance structure and standard operating procedures have earned it official biobank certification through the Canadian Tissue Repository Network. Herein, we describe the translational research gap that ISCIB is helping to fill; its structure, governance and certification; how data and samples are accrued, processed and stored; and finally, the process through which samples and data are shared with global researchers. The purpose of this paper describing ISCIB is to serve as an introductory guidance document for the wider community of SCI researchers. By helping researchers understand the contents of ISCIB and the process of accessing biospecimens, we seek to further ISCIB's vision as being a resource for human and translational research in SCI, with the ultimate goal of finding disease-modifying therapies for this disabling condition.

Ethical Challenges for Pediatric Biobanks.

Biobank participation of children is an ethically complicated process as the vulnerability of this population is a concern throughout the entire process of biobanking. Some ethical issues are more prominent in pediatric biobanking and may not need to be considered in biobanking of adult specimens and data. These include assent, reconsent at the age of majority, capacity to consent, and consequences of genetic results on the child and family members. This article describes current processes and best practices described in the literature as well as our experience at the BC Children's Hospital BioBank, a pediatric institutional biobank in Vancouver, Canada. The focus is on processes more specific to pediatric biobanking, such as assent, as well as topics that affect the pediatric population differently compared to adult biobanking.

Extracellular histones, a new class of inhibitory molecules of CNS axonal regeneration.

Axonal regeneration in the mature CNS is limited by extracellular inhibitory factors. Triple knockout mice lacking the major myelin-associated inhibitors do not display spontaneous regeneration after injury, indicating the presence of other inhibitors. Searching for such inhibitors, we have detected elevated levels of histone H3 in human CSF 24 h after spinal cord injury. Following dorsal column lesions in mice and optic nerve crushes in rats, elevated levels of extracellular histone H3 were detected at the injury site. Similar to myelin-associated inhibitors, these extracellular histones induced growth cone collapse and inhibited neurite outgrowth. Histones mediate inhibition through the transcription factor Y-box-binding protein 1 and Toll-like receptor 2, and these effects are independent of the Nogo receptor. Histone-mediated inhibition can be reversed by the addition of activated protein C in vitro, and activated protein C treatment promotes axonal regeneration in the crushed optic nerve in vivo. These findings identify extracellular histones as a new class of nerve regeneration-inhibiting molecules within the injured CNS.

Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia.

Several retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T, B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells) compartments. In a first evaluation of a cohort treated with Children's Oncology Group-based induction chemotherapy, the immune cell compartments were differentially depleted at D29. Neither gender, risk status, minimal residual disease, nor bone marrow recovery markers correlated with D29 ALC. In contrast, both CD3+ T cell and dendritic cell compartments, which did not correlate with age, significantly correlated with D29 ALC (p < 0.0001). In addition, subset complexity of cellular immune compartments was preserved at D29. This study reveals that D29 ALC significantly correlates with distinct immune cell compartments but not with bone marrow recovery markers, suggesting that higher D29 ALCs may contribute to leukemia control by inducing specific host immune activity.