Peripheral blood progenitor cell mobilization and leukapheresis in pigs.

Laboratory animal science Pub Date : 1999-12-01

K Nash, Q Chang, A Watts, S Treter, G Oravec, V Ferrara, L Buhler, M Basker, S Gojo, D H Sachs, M White-Scharf, J D Down, D K Cooper

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Abstract

Background and purpose: The pig is being investigated as an organ donor for humans. Induction of immunologic tolerance to pig tissues in primates would overcome the major immunologic barriers to xenotransplantation. A proven method of inducing tolerance to allografts is by the induction of mixed hematopoietic chimerism by bone marrow transplantation. We are therefore investigating induction of mixed hematopoietic chimerism in the pig-to-baboon model.

Methods: To obtain large numbers of pig hematopoietic cells, leukapheresis was used to collect blood cell products in miniature swine (n = 5) after progenitor cell mobilization by use of a course of hematopoietic growth factors (cytokines), consisting of porcine interleukin 3, porcine stem cell factor, and human granulocyte colony-stimulating factor.

Results: Cytokine therapy and leukapheresis were well tolerated. Cytokine therapy increased the total white blood cell count and allowed large numbers of leukocytes (60 x 10(10)) to be obtained by apheresis, of which approximately 0.1% were granulocyte-erythrocyte-monocyte-megakaryocyte colony-forming units (CFU-GEMMs), which are considered to be representative of hematopoietic progenitors with multi-lineage potential.

Conclusions: The combination of cytokine therapy and leukapheresis enables hematopoietic progenitor cells to be obtained safely from miniature swine.

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猪外周血祖细胞动员和白细胞分离。

背景和目的:猪正在被研究作为人类器官供体。在灵长类动物中诱导对猪组织的免疫耐受将克服异种移植的主要免疫障碍。一种已证实的诱导对同种异体移植物耐受的方法是通过骨髓移植诱导混合造血嵌合。因此，我们正在研究猪-狒狒模型中混合造血嵌合的诱导。方法:利用猪白细胞介素3、猪干细胞因子和人粒细胞集落刺激因子组成的造血生长因子(cytokines)动员祖细胞后，采用白细胞分离术采集5只小型猪的血细胞制品，以获得大量的猪造血细胞。结果:细胞因子治疗和白细胞摘除术耐受良好。细胞因子治疗增加了白细胞总数，并允许通过分离获得大量白细胞(60 × 10(10))，其中约0.1%是粒细胞-红细胞-单核细胞-巨核细胞集落形成单位(CFU-GEMMs)，被认为是具有多谱系潜力的造血祖细胞的代表。结论:细胞因子治疗与白细胞分离相结合，可安全获得小型猪造血祖细胞。

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Laboratory animal science

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