Elizabeth J. Abraham

Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter

The disease diabetes mellitus arises as a consequence of a failure of the beta-cells in the islets of Langerhans of the pancreas to produce insulin in the amounts required to meet the needs of the body. Whole pancreas or islet transplants in patients with severe diabetes effectively restore insulin production. A lack of availability of donor pancreata requires the development of alternative sources of islets such as the ex vivo culture and differentiation of stem/progenitor cells. Earlier we discovered multipotential progenitor cells in islets isolated from adult human pancreata that express the neural stem cell marker nestin: nestin-positive islet-derived progenitor cells (NIPs). Recently it was shown that the exclusion of the Hoechst 33342 dye, which defines the pluripotential side population (SP) of hematopoietic stem cells, is mediated by the ATP-binding cassette transporter, ABCG2. Here we report that the human islet-derived NIPs contain a substantial subpopulation of SP cells that co-express ABCG2, MDR1, and nestin. Thus NIPs may be a potential source of adult pluripotential stem/progenitor cells useful for the production of islet tissue for transplantation into diabetic subjects.

Human Pancreatic Islet-Derived Progenitor Cell Engraftment in Immunocompetent Mice

The potential for the use of stem/progenitor cells for the restoration of injured or diseased tissues has garnered much interest recently, establishing a new field of research called regenerative medicine. Attention has been focused on embryonic stem cells derived from human fetal tissues. However, the use of human fetal tissue for research and transplantation is controversial. An alternative is the isolation and utilization of multipotent stem/progenitor cells derived from adult donor tissues. We have previously reported on the isolation, propagation, and partial characterization of a population of stem/progenitor cells isolated from the pancreatic islets of Langerhans of adult human donor pancreata. Here we show that these human adult tissue-derived cells, nestin-positive islet-derived stem/progenitor cells, prepared from human adult pancreata survive engraftment and produce tissue chimerism when transplanted into immunocompetent mice either under the kidney capsule or by systemic injection. These xenografts seem to induce immune tolerance by establishing a mixed chimerism in the mice. We propose that a population of stem/progenitor cells isolated from the islets of the pancreas can cross xenogeneic transplantation immune barriers, induce tissue tolerance, and grow.

Research Biopsies: An Integrative Review of the Experiences of Patients With Cancer

BACKGROUND: Research biopsies (RBs) are essential to understanding tumor biology and mechanisms of resistance and to advancing precision medicine. However, RBs have associated risks and may not benefit the patient. OBJECTIVES: The purpose of this integrative review is to summarize and synthesize the current literature on the experience, attitudes, and understanding of patients with cancer related to RBs. METHODS: Articles from January 2010 to February 2017 were retrieved via a search of MEDLINE®. Articles included reported on the willingness, perceptions, understanding, attitudes, and/or experience of patients with cancer related to RBs. FINDINGS: Nine of 216 identified studies were selected. Studies exploring patient willingness to undergo RBs (n = 6) identified RBs as a potential barrier to clinical trial participation. Studies exploring patient understanding and informed consent (n = 3) revealed variable patient knowledge of the risks and benefits of RBs.

Equity of access: Consent interpretation program at Princess Margaret Cancer Centre (PM) in Canada.

189 Background: Toronto is a multicultural city with over 160 languages spoken by patients. Since 2010, institutional policy requires that professional medical interpreters are used when obtaining informed consent from patients with limited English proficiency (LEP). The availability and cost of these interpreters can be a deterrent for clinical trial participation, particularly when funding is limited. In order to ensure that patients facing language barriers have equitable access to trials, to protect the rights and safety of LEP patients involved in trials, and to improve patient outcomes, adherence to this policy needs to be ensured. METHODS Through a collaboration with the PM Cancer Clinical Research Unit (CCRU) and Interpretation and Translation Services (ITS) supported by the Princess Margaret Cancer Foundation, a 6-month pilot was initiated with full access to interpretation services for all trial patients in November 2012. The CCRU provided training to interpreters on clinical trials and GCP and interpreters reviewed template consent forms provided by ethics boards to cut back on preparation time and costs when delivering a sight translation of study specific consent forms. Trials staff were trained on the process and given badge tags with instructions. Metrics were collected to monitor the use of professional interpreters. RESULTS Utilization of professional interpreters in trials increased by 16% during the 6-month pilot and 286 requests have been logged to date. Staff were surveyed and indicate this has streamlined the consent process with 83% of respondents saying the new process is easy/very easy. Care providers feel this has allowed them to approach more patients than before this project. CONCLUSIONS This project ensures that accurate information is provided to all patients contemplating participating in or already enrolled in trials, that all patients have the same level of access to treatment, and that there is equity of access for all patients irrespective of their English proficiency. The increased use of professional interpreters in consent discussions indicates better adherence to policy which has allowed the pilot to continue for another year.