Department of Pathology, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
Dev Cell. 2013 May 28;25(4):333-49. doi: 10.1016/j.devcel.2013.04.016.
A dysfunctional bone marrow (BM) microenvironment is thought to contribute to the development of hematologic diseases. However, functional replacement of pathologic BM microenvironment through BM transplantation has not been possible. Furthermore, the study of hematopoietic inductive BM microenvironment is hampered by the lack of a functional nonhematopoietic reconstitution system. Here, we show that a deficiency of SH2-containing inositol-5'-phosphatase-1 (SHIP) in a nonhematopoietic host microenvironment enables its functional reconstitution by wild-type donor cells. This microenvironment reconstitution normalizes hematopoiesis in peripheral blood and BM and alleviates pathology of spleen and lung in the SHIP-deficient recipients. SHIP-deficient BM contains a significantly smaller population of multipotent stromal cells with distinct properties, which may contribute to the reconstitution by wild-type cells. We further demonstrate that it is the nonhematopoietic donor cells that are responsible for the reconstitution. Thus, we have established a nonhematopoietic BM microenvironment reconstitution system to functionally study specific cell types in hematopoietic niches.
功能失调的骨髓（BM）微环境被认为有助于血液疾病的发展。然而，通过骨髓移植对病理性 BM 微环境进行功能替代尚未成为可能。此外，由于缺乏功能性非造血重建系统，对造血诱导性 BM 微环境的研究受到阻碍。在这里，我们表明，在非造血宿主微环境中缺乏含 SH2 的肌醇 5'-磷酸酶-1（SHIP）能够使其被野生型供体细胞进行功能重建。这种微环境重建使外周血和 BM 中的造血正常化，并缓解 SHIP 缺陷受体内脾脏和肺部的病理。SHIP 缺陷的 BM 中含有明显较小比例的具有独特特性的多能基质细胞，这可能有助于由野生型细胞进行重建。我们进一步证明，是非造血供体细胞负责重建。因此，我们建立了非造血 BM 微环境重建系统，以功能研究造血龛位中的特定细胞类型。
