Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation
Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation
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DOI：
10.1182/blood.v95.11.3620.011k02_3620_3627
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发表时间：
2000-06-01
期刊：
影响因子：
20.3
通讯作者：
Zanjani, ED
中科院分区：
文献类型：
--
作者：
Almeida-Porada, G;Porada, CD;Zanjani, ED
子宫内和出生后造血干细胞（HSC）移植都将受益于提高植入水平或缩短重建所需时间的方法的开发。我们使用人羊造血干细胞移植的子宫内模型来研究改善移植后供体细胞的植入和分化的方法。我们假设，在移植的人类造血干细胞的同时提供更合适的人类基质细胞祖细胞形式的微环境将导致该异种模型中人类细胞的植入或分化率更高。这里提出的结果表明，自体和同种异体人类骨髓来源的基质细胞祖细胞的共同移植导致人类细胞在嵌合动物骨髓中的长期植入增强，并且在妊娠期间和出生后循环中更早和更高水平的供体细胞。通过使用标记的基质细胞，我们还证明了单独注射的基质细胞在绵羊造血微环境中植入并保持功能。将此方法应用于临床 HSC 移植可能会提高长期植入水平，缩短造血重建时间，并成为将外源基因传递到造血系统的一种方法。 （血液。2000；95：3620-3627）(C) 2000 年，美国血液学会。
Both in utero and postnatal hematopoietic stem cell (HSC) transplantation would benefit from the development of approaches that produce increased levels of engraftment or a reduction in the period of time required for reconstitution. We used the in utero model of human-sheep HSC transplantation to investigate ways of improving engraftment and differentiation of donor cells after transplantation. We hypothesized that providing a more suitable microenvironment in the form of human stromal cell progenitors simultaneously with the transplanted hu-man HSC would result in higher rates of engraftment or differentiation of the human cells in this xenogeneic model. The results presented here demonstrate that the cotransplantation of both autologous and allogeneic human bone marrow-derived stromal cell progenitors resulted in an enhancement of long-term engraftment of human cells in the bone marrow of the chimeric animals and in earlier and higher levels of donor cells in circulation both during gestation and after birth. By using marked stromal cells, we have also demonstrated that injected stromal cells alone engraft and remain functional within the sheep hematopoietic microenvironment. Application of this method to clinical HSC transplantation could potentially lead to Increased levels of long-term engraftment, a reduction in the time for hematopoietic reconstitution, and a means of delivery of foreign genes to the hematopoietic system. (Blood. 2000;95: 3620-3627) (C) 2000 by The American Society of Hematology.