Cell size and velocity of injection are major determinants of the safety of intracarotid stem cell transplantation
Cell size and velocity of injection are major determinants of the safety of intracarotid stem cell transplantation
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DOI：
10.1038/jcbfm.2013.32
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发表时间：
2013-06-01
影响因子：
6.3
通讯作者：
Walczak, Piotr
中科院分区：
文献类型：
--
作者：
Janowski, Miroslaw;Lyczek, Agatha;Walczak, Piotr
颈动脉内移植已经显示出将干细胞高效地输送到大脑的潜力。然而，已报道的并发症，如脑血流量下降(CBF)，促使我们进行进一步的安全性研究。用微导管将胶质细胞限制性前体细胞(GRPs)和间充质干细胞(MSCs)移植到大鼠颈内动脉(n=99)。磁共振成像用于检测移植后并发症，包括卒中的发展，以下实验变量：细胞大小、细胞剂量、细胞输注速度、动脉闭塞和细胞输注之间的延迟、不协调和协调异种移植以及颈内移植血流保留和受损。免疫相容和延迟输液不影响并发症的发生。输注速度超过1毫升/分钟常导致中风(44只动物中有27只)，即使输注赋形剂也是如此，而较低的输注速度(0.2毫升/分钟)对于输注赋形剂和较小的细胞(直径=15微米)都是安全的。大细胞(MSCs，直径=25微米)输注后，脑血流量显著降低(75+/-17%)。当注射2×10(6)的MSCs时，卒中病变频繁发生(15只动物中有12只)，但在将剂量降低到1×10(6)细胞后不会。目前的结果表明，细胞大小和输注速度是制定安全的颈动脉内干细胞移植方案的关键因素。
Intracarotid transplantation has shown potential for efficient stem cell delivery to the brain. However, reported complications, such as compromised cerebral blood flow (CBF), prompted us to perform further safety studies. Glial-restricted precursors (GRPs) and mesenchymal stem cells (MSCs) were transplanted into the internal carotid artery of rats (n = 99), using a microcatheter. Magnetic resonance imaging was used to detect post-transplantation complications, including the development of stroke, for the following experimental variables: cell size, cell dose, cell infusion velocity, delay between artery occlusion and cell infusion, discordant versus concordant xenografting, and intracarotid transplantation with preserved versus compromised blood flow. Immunocompatibility and delayed infusion did not affect the number of complications. An infusion velocity over >= 1 mL/minute often resulted in stroke (27 out of 44 animals), even with an infusion of vehicle, whereas a lower velocity (0.2 mL/minute) was safe for the infusion of both vehicle and smaller cells (GRPs, diameter = 15 mu m). Infusion of larger cells (MSCs, diameter = 25 mu m) resulted in a profound decrease (75 +/- 17%) in CBF. Stroke lesions occurred frequently (12 out of 15 animals) when injecting 2 x 10(6) MSCs, but not after lowering the dose to 1 x 10(6) cells. The present results show that cell size and infusion velocity are critical factors in developing safe protocols for intracarotid stem cell transplantation.