Multilineage Hematopoietic Expression in a Three-Dimensional Long Term Bone Marrow Culture System
The initial attempts to grow bone marrow cells in semi-solid or liquid medium promoted only the terminal differentiation of hematopoietic stem cells in the absence of self-renewal, with cultures becoming hematopoietically unproductive after 1–2 weeks of culture. Subsequent work in the murine system by Dexter and co-workers demonstrated that the sustained growth of hematopoietic cells in liquid culture was possible if these cells were plated onto a pre-established monolayer of bone marrow stromal cells3. These cells synthesize the matrix necessary to support hematopoiesis and contribute trophic/regulatory factors to the hematopoietic microenvironment. Inclusive of this group are fibroblasts, adipocytes reticular adventitial cells, macrophages, and endothelia4. The Dexter long-term bone marrow culture (LTBMC) system sustains the self renewal of murine pluripotential stem cells (CFU-S) although the lineage restricted progenitors become predominantly myeloid in character after the first several weeks of culture3,5. This system can be modulated to favor the growth of lymphoid cells6,7 or erythroid progenitors8, but single cultures do not produce substantial numbers of each hematologic cell type concurrently.
KeywordsCellulose Glycerol Leukemia Hydrocortisone Trypsin
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