Regulation of Myeloid and Lymphoid Development of Hematopoietic Stem Cells by Bone Marrow Stromal Cells

Abstract

Development of hematopoietic stem cells is regulated by stromal cells of the bone marrow. Many stromal cell lines have been established from temperature-sensitive SV40 large T-antigen gene transgenic mice and used to examine regulation of the purified stem cells. When the sorted stem cells were cocultured on the stromal cell layers, cobblestone formation was induced by the stromal cells. The cobblestones were formed by finite cell division (8 divisions on average) of sorted Lin- c-Kit+ Sca1+ stem cells committed to myeloid or lymphoid lineages. These stromal cell lines showed variable activities supporting the stem cell development. In one stromal cell line, TBR59, two waves of cobblestone formation committed to either myeloid lineage or lymphoid lineage were induced. TBR31-1, another bone marrow stromal cell line, induced only the cobblestone formation committed to lymphoid lineage. These results indicate that the bone marrow stromal cells selectively induce lineage-specific commitment of the stem cells. Both cobblestone formations require c-Kit function as well as adhesive interaction through VLA4 and VCAM1.

Macrophages and their subpopulations following allogeneic bone marrow transplantation for chronic myeloid leukaemia

“…With the exception of myelofibrosis [30] hardly anything is known about the other constituents of the bone marrow stroma responsible for the complex functional network composing the microenvironment, which exerts a significant impact on haematopoietic recovery and differentiation [23]. In this elaborate concert of various cell-to-cell and stromal matrix interactions, the resident macrophages deserve special attention.…”

Quantitative trait loci regulating relative lymphocyte proportions in mouse peripheral blood

“…[4][5][6] In addition, stromal cells, cytokines, receptors, ligands, signaling molecules, and transcription factors have been shown to affect levels of B and T lymphocytes. [7][8][9][10] Previous studies identified molecular factors that play important roles in the regulation of B-and T-cell commitment and balance such as cytokines interleukin-3 (IL-3) and IL-7, signaling receptor and ligand Notch and Jagged, paired-box gene Pax5, and the transcriptional factors E2A and EBF. 3,[11][12][13] Mutations that change the relative levels of other leukocyte subsets may also indirectly affect B-and T-cell proportions.…”

Therapy-related Changes of CD20+ and CD45RO+ Lymphocyte Subsets in Chronic Myeloid Leukemia (CML): An Immunohistochemical and Morphometric Study on Sequential Trephine Biopsies of the Bone Marrow

“…The second hypothesis on IFN action regards the fibrous interstitial matrix because several groups have shown definite alterations in the adhesive properties of CML progenitor cells to the marrow stroma layer. This pathomechanism may be responsible for the abnormal situation of a continuously occurring proliferation and differentiation of a (leukemic) cell population (44 -46) that is not subjected to the regulatory influences of the functionally complex modulation by the microenvironment (15,16). In this regard, IFN may act by correcting the defective adhesion to the bone marrow stroma, which in turn restores normal regulation of progenitor cell maturation and thus restitution of non-clonally transformed hematopoiesis (17).…”

“…Moreover, the paucity of lymphocytes within the hematopoietic tissue has significantly hampered any investigations attempting to elucidate alterations during chemotherapy or interferon administration. In vitro studies are in keeping with the assumption that the bone marrow stromal cells selectively induce a lineage-specific commitment of the myeloid and lymphoid progenitors (15,16). One of the effects of interferon-␣ (IFN) is to restore non-clonally transformed hematopoiesis in CML by a restitution of normal responsiveness to the negative regulation of the microenvironment (17)(18)(19).…”