Gonzalo-Daganzo Rosa, Regidor Carmen, Martín-Donaire Trinidad, Rico Miguel Angel, Bautista Guiomar, Krsnik Isabel, Forés Rafael, Ojeda Emilio, Sanjuán Isabel, García-Marco Jose A, Navarro Belen, Gil Santiago, Sánchez Rocio, Panadero Nuria, Gutiérrez Yolanda, García-Berciano Miguel, Pérez Nuria, Millán Isabel, Cabrera Rafael, Fernández Manuel N
Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Madrid, Spain.
Cytotherapy. 2009;11(3):278-88. doi: 10.1080/14653240902807018.
Cord blood (CB) transplants with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC) have been shown to result in 'bridge' engraftment with prompt neutrophil recovery and high final rates of CB engraftment and full chimerism. This strategy overcomes the limitation posed by low cellularity of CB units for unrelated transplants in adults. Enhancement of adaptive immunity reconstitution without increasing risks of graft-versus-host disease (GvHD) is required to optimize results further. Our objectives were to evaluate co-infusion of mesenchymal stromal cells (MSC) from the same TPD regarding tolerance, CB engraftment and effects on acute (a)GvHD, both preventive and therapeutic.
Ex vivo-expanded bone marrow MSC were infused at the time of the transplant or the in case of refractory aGvHD.
Nine patients received 1.04 - 2.15 x 10(6)/kg (median 1.20) MSC immediately after CB and TPD MHSC. Neither immediate adverse side-effects nor significant differences regarding CB engraftment or aGvHD development were observed. Four patients developed grade II aGvHD, refractory to steroids in two. These reached complete remission after therapeutic infusions of MSC.
In recipients of 'dual CB/TPD MHSC transplants', MSC infusions were therapeutically effective for severe aGvHD but no significant differences in CB engraftment and incidence of severe aGvHD were observed following their prophylactic use. Although results of this study alone cannot conclusively determine the application of MSC in CB transplantation, we believe that, in this setting, the best use of MSC could be as pre-emptive treatment for aGvHD.
脐血（CB）移植联合输注第三方供体（TPD）动员的造血干细胞（MHSC）已被证明可实现“桥梁”植入，中性粒细胞迅速恢复，CB植入和完全嵌合的最终率较高。该策略克服了成人无关移植中CB单位细胞数量少所带来的限制。为了进一步优化结果，需要在不增加移植物抗宿主病（GvHD）风险的情况下增强适应性免疫重建。我们的目标是评估来自同一TPD的间充质基质细胞（MSC）在耐受性、CB植入以及对急性（a）GvHD的预防和治疗作用方面的联合输注情况。
在移植时或难治性aGvHD情况下输注体外扩增的骨髓MSC。
9例患者在接受CB和TPD MHSC后立即接受了1.04 - 2.15 x 10(6)/kg（中位数1.20）的MSC输注。未观察到即刻不良副作用，在CB植入或aGvHD发生方面也未观察到显著差异。4例患者发生了II级aGvHD，其中2例对类固醇难治。在接受MSC治疗性输注后，这些患者达到了完全缓解。
在“双CB/TPD MHSC移植”受者中，MSC输注对严重aGvHD治疗有效，但预防性使用后在CB植入和严重aGvHD发生率方面未观察到显著差异。尽管仅本研究结果不能最终确定MSC在CB移植中的应用，但我们认为，在这种情况下，MSC的最佳用途可能是作为aGvHD的抢先治疗。
