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• Poster Text as presented at the 2013 World Congress of Neurology

  A BLOOD BRAIN BARRIER BIOREPOSITORY FOR DISEASE-SPECIFIC HUMAN BRAIN MICROVASCULAR ENDOTHELIAL CELLS: A NEW TOOL FOR NEUROLOGIC AND PSYCHIATRIC RESEARCH

  Thomas R. Roesel MD, PhD

  Cervoe.org

  OBJECTIVE
  The objective is two-fold: 1) to confirm the need for a biorepository for disease-specific human brain microvessel endothelial cells (HBMECs), and 2) to present a schematic for establishing the first blood brain barrier (BBB) bank to make available disease-specific HBMECs for clinically relevant translational medical research.

  BACKGROUND
  BBB dysfunction has been implicated in many illnesses of the central nervous system such as stroke (1,2), traumatic brain and spine injury (2,3,4), Parkinson's disease (5), Alzheimer's disease (6), schizophrenia (2,7,8), multiple sclerosis (9), as well as more uncommon conditions such as chronic Lyme disease (10,11), chronic fatigue syndrome (12), Gulf War-related illness (13), and human immune deficiency virus (HIV) associated dementia (HAD) (6,14). Investigations on BBB pathophysiology are restricted by the inability to construct in vitro BBB culture experiments using disease-specific HBMECs due to the lack of their on demand availability, despite the routine availability of normal, non-disease related HBMECs.

  METHODS
  Non-oncological brain tissue banks throughout the world were identified through literature and website searches. These repositories were evaluated to determine whether their services included the isolation of disease specific HBMECs for dissemination to researchers not affiliated with the HBMEC procurement process. This information was obtained by scrutiny of the identified biorepository website and/or by direct email query to that repository. Furthermore, the scientific literature was reviewed for HBMEC isolation and cryopreservation techniques, as routinely utilized by HBMEC providers for the procurement of normal, nonspecific HBMECs, to develop a protocol for the banking of disease-specific HBMECs.

  RESULTS
  Seventy-nine non-oncological brain banks or their umbrella networks in 16 different countries were identified by literature and website searches. In addition, 8 commercial vendors for HBMECs were similarly identified. Neither the commercial or non-commercial brain tissue banks offered disease-specific HBMECs for laboratory investigations. However, 11 non-commercial banks could provide disease-specific HBMECs with advanced notification, should a disease appropriate donor become available.

  DISCUSSION
  With the lack of availability of a biorepository committed to supplying disease-specific HBMECs on demand, a construct for such a repository was developed. The proposed biorepository is based on current principles that govern established tissue bank repositories as followed by commercial and non-commercial vendors which provide HBMECs that lack disease specificity (15). Biorepository functions are divided into administrative, laboratory, and cryopreservation storage areas. Personnel can have overlapping duties in each of these areas, but physical barriers between the designated areas should exist to avoid sample contamination. Administrators help to recruit volunteer donors, obtain pre-endowment consent, and acquire medical history before and at the time of death. Post-death consent from the family is required and donor encryption principles are followed. Administrators also disseminate to the investigator, who request samples, the medical history related to the disease-specific HBMECs under policies that assure donor privacy. Tissue acquisition and HBMEC isolation follow established procedures for all volunteer brain endowments (16,17). Tissue and cell handling, assessment and documentation of the “state of the brain,” including photography, and subsequent dissection of the cerebral brain microvessels are performed by laboratory personnel. The microvessels from disease affected areas of the brain as well as non-disease affected control areas, when necessary, are processed so that HBMECs are isolated. These disease- specific HBMECs are then placed into appropriately labeled vials and cryopreserved for storage by standard procedures until dissemination to the requesting investigators (16,17). Donor confidentiality is maintained at all times.

  CONCLUSIONS
  Establishment of a biorepository for cryopreserved disease-specific HBMECs is feasible, and can provide needed cells for BBB-related translational medicine studies in neurology and psychiatry. There are currently no such banks dedicated to providing disease-specific HBMECs. Using such cells to increase pathophysiologic knowledge and to discover interventions to increase BBB resiliency for specific diseases can be explored with on-demand disease-specific HBMECs. Efforts are underway to establish the first such biorepository.

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