Successful allogeneic bone marrow transplantation by injection of bone marrow stromal cells and the cytological and molecular-biological analyses of their role

我们以前发现骨髓移植可以用于治疗自身免疫性疾病，即使是嵌合体抵抗的组合，如[Normal→MRL/1PR]和[DAB/2→C57BL/6]，骨髓移植也可以通过骨髓移植加骨移植获得成功(《免疫学杂志》152：3991,1994和Exp.hematol.23：347,1995)。供体骨髓基质细胞(BMSCs)部分被供体类型的BMSCs替代，表明供体来源的BMSCs从移植骨向受体骨迁移，为供体造血干细胞(HSCs)提供了适宜的环境。我对骨髓间充质干细胞作为骨髓移植促进细胞的作用进行了研究，得到了以下结果：1.骨髓移植加骨移植后，供者来源的骨髓间充质干细胞可以迁移到受者胸腺并参与阳性选择(Exp。血醇。2.与培养3-4周后获得的供体BMSCs一起，经门静脉途径(PV)注入受体小鼠脾内的造血祖细胞集落形成显著增加，最终获得较高的存活率(静脉途径不能)。这些小鼠的肝脏中确实存在由供者造血细胞和骨髓间充质干细胞组成的造血集落。这些发现表明，被捕获的BMSCs和HSCs确实在肝脏中形成造血集落，然后迁移到受者的骨髓和脾中形成CFU-S(干细胞19：144,2001)。3.通过PV途径移植骨髓细胞，然后通过IV途径额外给药，即使在嵌合抵抗组合(干细胞在按下)中也能导致成功的重建。4.MHC Ia类(H-2 K和D位点)决定了HSC和BMSCs之间的限制(Stem Cells 19：46,2001)。

We have previously found that bone marrow transplantation (BMT) can be used to treat autoimmune diseases and that successful BMT can be achieved by BMT plus bone grafts even if in chimerism-resistant combinations such as [normal→ MRL/1pr] and [DAB/2→C57BL/6] (J.Immunol.152 : 3991, 1994 ＆ Exp.Hematol.23 : 347, 1995). Bone marrow stromal cells (BMSCs) of the recipients are replaced partially by donor-type BMSCs, indicating that donor-derived BMSCs migrate from the engrafted bones to the recipient bones and offer a suitable environment for donor hemopoietic stem cells (HSCs). I have investigated the role of BMSCs as BMT-facilitating cells and obtained the following results.1.After BMT plus bone grafts, donor-derived BMSCs can migrate into recipient thymus and participate there in positive selection (Exp. Hematol. 28 : 950, 2000).2.When recipient mice were injected HSCs along with donor BMSCs obtained after 3-4 week-culture, by portal vein (PV) route, hemopoietic colony fomation was markedly increased in the recipient spleen and finally higher survival rate could be achieved (but not intravenous (IV) route). Hematopoietic colonies composed of both donor hemopoietic cells and BMSCs do exist in the liver of these mice. These findings suggest trapped BMSCs and HSCs do form hemopoietic colonies in the liver and then migrate into recipient bone marrow and spleen to form CFU-S (Stem Cells 19 : 144, 2001).3.BMT of bone marrow cells by PV route, followed by additional administration of bone marrow cells by IV route, leads a successful reconstitution even if in chimerism-resistant combinations (Stem Cells in press).4.MHC class Ia (H-2 K and D loci) determines the restriction between HSCs and BMSCs (Stem Cells 19 : 46, 2001).