Sol J C, Sallerin B, Larrue S, Li R Y, Jozan S, Tortosa F, Mascott C, Carraoue F, Tafani M, Lazorthes Y
Laboratory of Pain and Cell Therapy, Rangueil Medical School, 31062 Toulouse, Cedex, France.
Exp Neurol. 2004 Apr;186(2):198-211. doi: 10.1016/j.expneurol.2003.10.018.
Adrenal medullary chromaffin cells synthetize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. Previous reports have shown that implantation of chromaffin cells into the spinal subarachnoid space can reduce both acute and chronic pain in several animal models. We recently demonstrated that human chromaffin cell grafts in the cerebrospinal fluid (CSF) could alleviate intractable cancer pain after failure of systemic opiates. However, wider application of this approach was limited by the limited availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as bovine adrenal medulla were successful in the experimental treatment of pain, but recent concern over risk of prion transmission precluded use of bovine grafts in human clinical trials. The objective of the present study was to investigate the possibility of developing a new xenogeneic porcine source of therapeutic chromaffin cells because this strategy is currently considered the safest for transplantation in man. In the present study, we report the isolation and the characterization of primary porcine chromaffin cells (PCC) compared to bovine cells. We show, for the first time, that these cells grafted in the rat subarachnoid space can attenuate pain-related behaviors as assessed by the formalin test, a model of tonic pain. Moreover, in addition to behavioral studies, immunohistochemical analysis revealed robust survival of chromaffin cells 35 days after transplantation. Taken together, these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.
肾上腺髓质嗜铬细胞合成并分泌包括儿茶酚胺和阿片肽在内的多种具有止痛作用的神经活性化合物。先前的报道表明，将嗜铬细胞植入脊髓蛛网膜下腔可减轻多种动物模型中的急性和慢性疼痛。我们最近证明，在全身使用阿片类药物无效后，将人嗜铬细胞移植到脑脊液（CSF）中可缓解顽固性癌症疼痛。然而，由于同种异体供体材料的可用性有限，这种方法的更广泛应用受到了限制。另外，来自异种来源（如牛肾上腺髓质）的嗜铬细胞在疼痛的实验治疗中取得了成功，但最近对朊病毒传播风险的担忧使得牛移植细胞无法用于人类临床试验。本研究的目的是探讨开发一种新的异种猪源治疗性嗜铬细胞的可能性，因为目前认为这种策略对人类移植是最安全的。在本研究中，我们报告了与牛细胞相比，原代猪嗜铬细胞（PCC）的分离和特性。我们首次表明，将这些细胞移植到大鼠蛛网膜下腔后，通过福尔马林试验（一种持续性疼痛模型）评估，可减轻疼痛相关行为。此外，除了行为学研究，免疫组织化学分析显示移植后35天嗜铬细胞存活良好。综上所述，这些结果支持了猪嗜铬细胞可能为传递止痛神经活性物质的移植提供一种异种细胞来源的概念。
