Wang H, Sagen J
Department of Anatomy and Cell Biology, University of Illinois at Chicago 60612.
J Neural Transplant Plast. 1994 Jan-Mar;5(1):49-64. doi: 10.1155/NP.1994.49.
Previous findings in our laboratory have demonstrated that transplants of adrenal medullary tissue into the spinal subarachnoid space can alleviate pain, most likely via sustained local release of pain-reducing neuroactive substances from the transplanted chromaffin cells. The success of this work in animal models has led to preliminary clinical trials with promising results. However, before large-scale clinical studies are undertaken, numerous issues should be resolved, many of which can be readily addressed initially in the laboratory. One of these is the amount of donor adrenal medullary tissue necessary to produce long-term antinociception. Although tissue from two adrenal glands has generally been used, it is unknown whether less would be equally effective, or more could increase analgesic potency. To address this, various amounts of adrenal medullary tissue, ranging from one to ten donor glands, were used. Results showed lowered antinociceptive benefits when only one adrenal medulla was used, but only small and short-lived increases when donor material was increased substantially. In addition, assays of catecholamine and Met-enkephalin release in the host spinal CSF revealed only slight further increases following the transplantation of more than 2-4 glands. These results indicate that a small amount of adrenal medullary tissue is necessary and sufficient to produce sustained antinociception, and suggest that higher amounts may result in tolerance development or feedback inhibition. Another important issue is the ability to retain antinociceptive potency if donor tissue is maintained in culture prior to transplantation, since the coordination of donor harvesting and recipient availability is often difficult. To address this, donor adrenal medullary tissue was maintained in explant culture for various periods following dissection. Results indicated that adrenal medullary tissue can be maintained in culture for up to 30 days prior to transplantation without decrement in antinociceptive potency, and that a period of 7-21 days results in improved graft viability. Results of this study indicate that some of the critical issues for successful neural transplantation outcomes can be initially addressed in pre-clinical studies.
我们实验室之前的研究结果表明，将肾上腺髓质组织移植到脊髓蛛网膜下腔可以减轻疼痛，最有可能是通过移植的嗜铬细胞持续局部释放减轻疼痛的神经活性物质。这项工作在动物模型中的成功已导致进行了初步临床试验并取得了有希望的结果。然而，在进行大规模临床研究之前，许多问题需要解决，其中许多问题可以首先在实验室中轻松解决。其中一个问题是产生长期抗伤害感受所需的供体肾上腺髓质组织的量。虽然通常使用来自两个肾上腺的组织，但尚不清楚较少的组织是否同样有效，或者更多的组织是否可以提高镇痛效力。为了解决这个问题，使用了从一到十个供体肾上腺的各种量的肾上腺髓质组织。结果表明，仅使用一个肾上腺髓质时抗伤害感受益处降低，但当供体材料大量增加时，仅出现微小且短暂的增加。此外，宿主脊髓脑脊液中儿茶酚胺和甲硫氨酸脑啡肽释放的测定显示，移植超过2 - 4个腺体后仅略有进一步增加。这些结果表明，少量的肾上腺髓质组织对于产生持续的抗伤害感受是必要且充分的，并表明更多的量可能导致耐受性发展或反馈抑制。另一个重要问题是，如果供体组织在移植前保存在培养物中，是否能够保持抗伤害感受效力，因为供体采集和受体可用性的协调通常很困难。为了解决这个问题，在解剖后将供体肾上腺髓质组织在器官培养物中保存不同时间。结果表明，肾上腺髓质组织在移植前可以在培养物中保存长达30天而不降低抗伤害感受效力，并且7 - 21天的保存期可提高移植物的活力。这项研究的结果表明，成功的神经移植结果的一些关键问题可以首先在临床前研究中得到解决。
