RESUMO
The Ontario Cancer Research Ethics Board (ocreb) has made its mark within Ontario as a successful, centralized, oncology-specific research ethics board. As such, ocreb has proven invaluable to principal investigators, sponsors, and study participants given its ability to reduce duplication during the submission process, to provide the highest quality of review, to shorten study start-up time, and to implement more efficient methods of reporting serious adverse events.
RESUMO
Long-term bone marrow cultures (LTBMC) serve as a valuable in vitro model of the bone marrow microenvironment. The stromal layer supports the growth of immature and mature cell populations through production of colony-stimulating factors and cell:cell interactions. LTBMC are devoid of mature lymphoid cells but contain stem cells capable of restoring lymphoid and myeloid function in suitable recipients. Severe combined immune deficiency (scid) mice provide a useful environment to study lymphocyte development, as their autosomal recessive mutation on chromosome 16 leaves them with a severe deficiency of B and T lymphocytes. To determine the presence of different classes of stem cells in LTBMC, adherent cells from the cultures were grafted into sublethally irradiated scid mice and lineage reconstitution was evaluated 6 weeks to 3 months postengraftment. Self-renewal of donor stem cells was tested by serial transfer of scid bone marrow to donor secondary C.B-17 and scid recipients. Mature lymphoid and myeloid cells were isolated from reconstituted mice and a restriction fragment length polymorphism (RFLP) at the Cmu immunoglobulin locus was used to distinguish donor and host cells. We found that LTBMC contained both long-term and short-term reconstituting stem cells. The long-term stem cells had significant self-renewal potential and fully reconstituted all lineages in both primary and secondary recipients The short-term stem cells produced mostly lymphoid progeny at the time of analysis and their limited self-renewal capacity led to partial reconstitution of only the primary recipients. The short-term reconstituting cells may be lymphoid-restricted stem cells
