Vormoor J, Lapidot T, Pflumio F, Risdon G, Patterson B, Broxmeyer H E, Dick J E
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Blood Cells. 1994;20(2-3):316-20; discussion 320-2.
Cord blood is increasingly used as an alternative stem cell source for autologous and allogeneic transplantation, particularly in pediatric patients. We therefore adopted our protocol for transplanting human adult bone marrow cells into severe combined immunodeficient (SCID) mice [1] to develop an in vivo model for cord blood hematopoiesis. Intravenous injection of unfractionated or Ficoll-separated cord blood cells into sublethally irradiated SCID mice led to high levels of human hematopoiesis in the majority of the recipients [2]. Multilineage human hematopoiesis including committed and multipotential myeloerythroid progenitors as well as CD19+ B-lymphoid cells were observed in the murine bone marrow for at least 18 weeks. Together, these data indicate that the SCID mice were engrafted with an immature cell that was able to maintain multiple progenitor lineages in vivo. In contrast to our experiences with adult bone marrow, high levels of human cell engraftment in the mouse could be achieved without exogenous cytokine treatment, suggesting that the cord blood cells respond differently to the murine microenvironment. Alternatively, the cord blood cells might have been able to provide themselves with the necessary growth factors in a paracrine fashion. This model will be useful in gaining new insights into the biology of immature human cord blood progenitors and cord blood transplantation.
脐血越来越多地被用作自体和异体移植的替代干细胞来源,尤其是在儿科患者中。因此,我们采用了将人类成人骨髓细胞移植到严重联合免疫缺陷(SCID)小鼠体内的方案[1],以建立一个脐血造血的体内模型。将未分级或经Ficoll分离的脐血细胞静脉注射到亚致死剂量照射的SCID小鼠体内,导致大多数受体中出现高水平的人类造血现象[2]。在小鼠骨髓中观察到多谱系人类造血,包括定向和多能髓系红系祖细胞以及CD-19+B淋巴细胞,持续至少18周。总之,这些数据表明SCID小鼠植入了一种能够在体内维持多个祖细胞谱系的未成熟细胞。与我们在成人骨髓方面的经验不同,无需外源性细胞因子治疗就能在小鼠体内实现高水平的人类细胞植入,这表明脐血细胞对小鼠微环境的反应不同。或者,脐血细胞可能能够以旁分泌方式为自身提供必要的生长因子。该模型将有助于深入了解未成熟人类脐血祖细胞的生物学特性和脐血移植。