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Recovery of Donor Hematopoiesis after Graft Failure and Second Hematopoietic Stem Cell Transplantation with Intraosseous Administration of Mesenchymal Stromal Cells

机译:移植失败和第二次造血干细胞移植与间质基质细胞的骨内给药后供体造血功能的恢复

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Multipotent mesenchymal stromal cells (MSCs) participate in the formation of bone marrow niches for hematopoietic stem cells. Donor MSCs can serve as a source of recovery for niches in patients with graft failure (GF) after allogeneic bone marrow (BM) transplantation. Since only few MSCs reach the BM after intravenous injection, MSCs were implanted into the iliac spine. For 8 patients with GF after allo-BMT, another hematopoietic stem cell transplantation with simultaneous implantation of MSCs from their respective donors into cancellous bone was performed. BM was aspirated from the iliac crest of these patients at 1-2, 4-5, and 9 months after the intraosseous injection of donor MSCs. Patients’ MSCs were cultivated, and chimerism was determined. In 6 out of 8 patients, donor hematopoiesis was restored. Donor cells (9.4 ± 3.3%) were detected among MSCs. Thus, implanted MSCs remain localized at the site of administration and do not lose the ability to proliferate. These results suggest that MSCs could participate in the restoration of niches for donor hematopoietic cells or have an immunomodulatory effect, preventing repeated rejection of the graft. Perhaps, intraosseous implantation of MSCs contributes to the success of the second transplantation of hematopoietic stem cells and patient survival.
机译:多能间质基质细胞(MSCs)参与造血干细胞骨髓壁的形成。供体间充质干细胞可以作为异体骨髓(BM)移植后移植失败(GF)患者的利基恢复来源。由于静脉注射后只有很少的MSC到达BM,因此将MSC植入into骨。对于8名异基因BMT后的GF患者,进行了另一次造血干细胞移植,同时将其各自供体的MSC同时植入到松质骨中。骨内注射供体MSC后1-2、4-5和9个月从这些患者的the中吸出BM。培养患者的MSC,并确定嵌合体。 8例患者中有6例恢复了造血功能。在MSC中检测到供体细胞(9.4±±3.3%)。因此,植入的MSC保持局限在给药部位,并且不丧失增殖能力。这些结果表明,MSC可以参与供体造血细胞壁ni的恢复或具有免疫调节作用,从而防止移植物的反复排斥。也许,MSCs的骨内植入有助于造血干细胞第二次移植的成功以及患者的存活。

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