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

我们之前已经发现骨髓移植（BMT）可以用于治疗自身免疫性疾病，并且BMT加骨移植可以成功地实现BMT，即使是嵌合抵抗的组合，如[正常→MRL/1pr]和[DAB/2→C57BL/6] （j . immuno1）。[15] [j] .中华医学会。23: 347, 1995)。受体的骨髓间质细胞（BMSCs）部分被供体型骨髓间质细胞取代，表明供体来源的骨髓间质细胞从移植骨向受体骨迁移，并为供体造血干细胞（hsc）提供了合适的环境。我研究了骨髓间充质干细胞作为骨髓转化促进细胞的作用，得到了以下结果：骨髓间充质干细胞移植后，供体来源的骨髓间充质干细胞可以迁移到受体胸腺并参与阳性选择（实验血液学杂志，28:950,2000）。将造血干细胞与培养3-4周后获得的供体骨髓间充质干细胞一起经门静脉（PV）途径注射后，受体小鼠脾脏内造血集落形成明显增加，最终获得更高的存活率（静脉（IV）途径没有）。由供体造血细胞和骨髓间充质干细胞组成的造血集落确实存在于这些小鼠的肝脏中。这些发现表明，被困的骨髓间充质干细胞和造血干细胞确实在肝脏形成造血集落，然后迁移到受体骨髓和脾脏形成CFU-S（干细胞19:144,2001）。通过PV途径对骨髓细胞进行BMT，然后通过IV途径对骨髓细胞进行额外的管理，即使在嵌合抵抗组合中也能成功地重建（干细胞出版）。MHC Ia类（h - 2k和D位点）决定了造血干细胞和骨髓间充质干细胞之间的限制（干细胞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).