Manzanedo Ana, Rodriguez Fidel, Obeso Jose A, Rodriguez Manuel
Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, Faculty of Medicine, University of La Laguna , La Laguna, Tenerife, Canary Islands , Spain.
† Department of Pharmacology and Physical Medicine, Faculty of Medicine, University of La Laguna , La Laguna, Tenerife, Canary Islands , Spain.
Cell Med. 2010 Nov 5;1(2):93-103. doi: 10.3727/215517910X528969. eCollection 2010.
The ability of bone marrow cells (BMCs) to migrate to different organs can be used for indirect cell therapy, a procedure based on the engraftment of therapeutic cells in a different place from where they will finally move to and perform their action and which could be particularly useful for chronic illness where a persistent and long-lasting therapeutic action is required. Thus, establishing a stable colony of engineered BMCs is a requisite for the chronic provision of damaged tissues with engineered cells. Reported here is a procedure for creating such a cell colony in a portion of the bone marrow (BM). The study was performed in C57BL/6j mice and consisted of developing a focal niche in a portion of the bone marrow with focal irradiation so that it could be selectively colonized by BM cells (C57BL/6-FG-VC-GFP mice) injected in the blood stream. Both the arrival of cells coming from the nonirradiated BM (week 1 after irradiation) and the proliferation of cells in the irradiated BM (week 2) prevented the homing of injected cells in the BM niche. However, when BMCs were injected in a time window about 48 h after irradiation they migrated to the BM niche where they established a cell colony able to: 1) survive for a long period of time [the percentage of injected cells increased in the BM from day 30 postinjection (15%) to day 110 postinjection 28%)]; 2) express cell differentiation markers (90% of them were lineage committed 4 weeks after engraftment); and 3) colonize to the blood stream (with 5% and 9% of all blood cells being computed 1 and 3 months after engraftment, respectively). The intravenous injection of BMCs in combination with a previous transitory focal myeloablation is a safe and easy method for creating the long-lasting colony of modified BMCs needed for treating chronic and progressive illness with indirect cell therapy.
骨髓细胞（BMCs）迁移至不同器官的能力可用于间接细胞治疗，该方法基于治疗性细胞在其最终发挥作用的部位以外的其他地方植入，这对于需要持续长期治疗作用的慢性疾病可能特别有用。因此，建立稳定的工程化BMCs集落是向受损组织长期提供工程化细胞的必要条件。本文报道了一种在部分骨髓（BM）中创建此类细胞集落的方法。该研究在C57BL/6j小鼠中进行，包括通过局部照射在部分骨髓中形成一个局部微环境，以便其能够被注入血流中的BM细胞（C57BL/6-FG-VC-GFP小鼠）选择性地定植。来自未照射骨髓的细胞的到达（照射后第1周）和照射骨髓中细胞的增殖（第2周）均阻止了注入细胞在骨髓微环境中的归巢。然而，当在照射后约48小时的时间窗内注射BMCs时，它们迁移至骨髓微环境并在其中建立了一个能够：1）长期存活[从注射后第30天（15%）到注射后第110天（28%），骨髓中注入细胞的百分比增加]；2）表达细胞分化标志物（移植后4周，其中90%的细胞已定向分化）；3）定植至血流（移植后1个月和3个月，分别计算所有血细胞的5%和9%）的细胞集落。将BMCs静脉注射与先前的短暂局部骨髓消融相结合，是一种安全简便的方法，可用于创建间接细胞治疗慢性进行性疾病所需的经修饰BMCs的长期集落。
