Quinones R R
Children's Hospital National Medical Center, George Washington University School of Medicine, Washington, DC 20010.
Am J Pediatr Hematol Oncol. 1993 Feb;15(1):3-17. doi: 10.1097/00043426-199302000-00002.
This article reviews the complex process of establishing functional long-term hematopoiesis required for successful clinical bone marrow transplantation. The failure to establish sustained hematopoiesis, either primary or secondary graft failure, is defined and multiple etiologic factors involved are discussed.
Data from published studies of experimental and clinical BMT, as well as in vitro stem cell biology, were used to elucidate the elements required for establishing functional hematopoiesis. These include pleuripotential hematopoietic stem cells; homing of stem cell to the hematopoietic micro-environment; hematopoietic stroma and secreted cytokines acting synergistically to promote expansion and hematopoietic differentiation of the stem cells; and, in the setting of allogeneic transplantation, immunological tolerance between the host and the graft, without which graft rejection or graft-vs.-host disease may occur.
The factors influencing the establishment of functional hematopoiesis and the risks for graft failure vary with the type of transplant performed. In an autologous transplant, damage to the stem cells or to the stromal microenvironment can contribute to prolonged time to engraftment or primary graft failure. In contrast, the hematopoietic stem cells are normal in both syngeneic and allogeneic transplantation. However, in the latter, because of immunological disparity between the host and recipient, there can be either primary or secondary graft failure due to a host-vs.-graft phenomenon, graft rejection. Classic graft rejection is an immunologic phenomenon mediated by residual host immunocompetent cells, either T cells or NK cells, depending on the allogeneic disparity between host and donor. T cell depletion and increased HLA disparity are risk factors for rejection. Numerous strategies have attempted to decrease the risk of rejection; most have focused primarily on increased immunosuppression of the host either with additional radiation, chemotherapy or in vivo anti-T cell serotherapy. Recent attempts have explored preventing rejection by manipulating donor cell composition of the infused graft.
本文回顾了成功进行临床骨髓移植所需的功能性长期造血建立的复杂过程。定义了未能建立持续造血，即原发性或继发性移植物失败，并讨论了所涉及的多种病因因素。
来自已发表的实验性和临床骨髓移植研究以及体外干细胞生物学的数据，用于阐明建立功能性造血所需的要素。这些要素包括多能造血干细胞；干细胞归巢至造血微环境；造血基质和分泌的细胞因子协同作用以促进干细胞的扩增和造血分化；以及在同种异体移植情况下，宿主与移植物之间的免疫耐受，否则可能发生移植物排斥或移植物抗宿主病。
影响功能性造血建立的因素和移植物失败的风险因所进行的移植类型而异。在自体移植中，干细胞或基质微环境的损伤可导致植入时间延长或原发性移植物失败。相比之下，同基因和同种异体移植中的造血干细胞都是正常的。然而，在同种异体移植中，由于宿主与受者之间的免疫差异，可能会因宿主抗移植物现象即移植物排斥而出现原发性或继发性移植物失败。经典的移植物排斥是一种由残留的宿主免疫活性细胞介导的免疫现象，取决于宿主与供体之间的同种异体差异，这些细胞可以是T细胞或NK细胞。T细胞清除和HLA差异增加是排斥的危险因素。许多策略试图降低排斥风险；大多数主要集中在通过额外的放疗、化疗或体内抗T细胞血清疗法增加宿主的免疫抑制。最近的尝试探索了通过操纵输注移植物的供体细胞组成来预防排斥。
