Cellular therapies supplement: the peritoneum as an ectopic site of hematopoiesis following in utero transplantation.

Cellular therapies supplement: the peritoneum as an ectopic site of hematopoiesis following in utero transplantation.
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细胞疗法补充:腹膜作为子宫移植后造血的异位部位。

DOI:
10.1111/j.1537-2995.2011.03373.x
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发表时间:
2011
期刊:
影响因子:
2.9
通讯作者:
Fomin,MarinaE
Fomin,MarinaE
中科院分区:
医学3区
文献类型:
--
作者:
Muench,MarcusO;Chen,Jeng-Chang;Beyer,AshleyI;Fomin,MarinaE

文献摘要

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背景:子宫内移植(IUT)有可能在免疫系统完全发育之前早期治疗出生缺陷。相对较小的移植物,这是不匹配的主要组织相容性抗原,甚至可以在疾病症状发作之前交付。造血干细胞的IUT通常通过腹膜内注射进行,但供体细胞在腹膜腔中的命运尚未完全了解。我们回顾了我们最近的工作,并提出了新的数据表明,腹膜可以异位造血与IUT和免疫耐受induction.Study设计和方法的影响的网站:单倍和同种异体胎儿移植在小鼠和移植跟踪流式细胞术。通过混合淋巴细胞反应和皮肤移植研究免疫耐受。成年同基因小鼠移植和异种人到免疫缺陷小鼠移植进行以下造血滞留在腹膜和植入的marrow.Results:虽然大多数移植的细胞迅速清除腹膜,造血细胞和造血前体细胞的表型可以留在腹腔移植后数月。供体细胞在腹膜中的存在有助于供体特异性耐受,但需要足够的外周血嵌合体以确保供体皮肤grafts.CONCLUSION:异位造血和腹膜中干细胞的存活提供了更好地利用腹膜腔递送干细胞并促进对同种异体抗原或其他外源抗原的免疫耐受的可能性。
BACKGROUND:In utero transplantation (IUT) has the potential to treat birth defects early before full development of the immune system. Relatively small grafts, which are not matched for major histocompatibility antigens, can be delivered even before onset of disease symptoms. IUT of hematopoietic stem cells is usually performed via intraperitoneal injection, yet the fate of donor cells in the peritoneal cavity is not fully understood. We review our recent work and present new data demonstrating that the peritoneum can be a site of ectopic hematopoiesis with implications for IUT and immune tolerance induction.STUDY DESIGN AND METHODS:Haplogeneic and allogeneic fetal transplants were performed in mice and engraftment tracked by flow cytometry. Immune tolerance was studied by mixed lymphocyte reactions and skin transplantation. Adult syngeneic murine transplants and xenogeneic human into immunodeficient mouse transplants were performed to follow hematopoietic retention in the peritoneum and engraftment of the marrow.RESULTS:Although most transplanted cells rapidly clear the peritoneum, hematopoietic cells and cells with the phenotype of hematopoietic precursors can remain in the peritoneal cavity for months after transplant. The presence of donor cells in the peritoneum can contribute to donor‐specific tolerance, but sufficient peripheral blood chimerism is required to ensure acceptance of donor skin grafts.CONCLUSION:Ectopic hematopoiesis and the survival of stem cells in the peritoneum offer the possibility of better using the peritoneal cavity to delivery stem cells and foster the development of immune tolerance to alloantigens or other foreign antigens.