López-Lozano J J, Bravo G, Abascal J, Brera B, Pascual M L, Martínez R, de la Torre C, Moreno R
CPH Neural Transplantation Group (Departments of Neurology, Neurosurgery, Surgery and Laboratory Neurobiology), Clínica Puerta de Hierro, Madrid, Spain.
Transpl Int. 1996;9 Suppl 1:S485-91. doi: 10.1007/978-3-662-00818-8_116.
Coimplants of adrenal medulla (AM) and peripheral nerve (PN) in animal models of Parkinson's disease (PD) have shown that AM cells survive longer, tend to show neuronal phenotype, and enhance sprouting of host fibers. Since 1987, our implants of perfused AM and fetal ventral mesencephalon (FVM) in PD patients have achieved varying degrees of clinical improvement. If the donor tissue determines the improvement, different types of implants should result in qualitatively and quantitatively different degrees of improvement. The purpose of this study is to determine whether or not the clinical course, improvement slope, and reduction of medication observed in PD patients who undergo tissue transplantation (Tx) depend on the donor tissue type. In a pilot study, four grade IV-V PD patients received implants of precoincubated autologous AM and intercostal nerve in the caudate nucleus (open surgery). Clinical assessment was based on international scales (UPD) as reported for Tx of FVM and perfused AM. There were no systemic or neurologic complications. Four years post-Tx, longer On phases and improved PD symptoms (ADL and motor-UPD) in On and Off persist in four cases, with reduced dyskinesias. Progress appears to be stepwise, starting within weeks of Tx (similar to AM and sooner than our FVM implants), followed by a period of stability and, after a second wave of improvement 12-18 months post-Tx (similar to FVM implants), continues to date. L-dopa medication has been reduced by more than 60% and dopamine agonist use has not resumed. We conclude that our recipients continue to be clinically better than prior to Tx. The course of recovery after co-Tx of AM and PN differs from that of FVM or AM implants. This fact may be related to the etiological factors that produce the improvement.
在帕金森病(PD)动物模型中,肾上腺髓质(AM)与周围神经(PN)的联合植入已表明,AM细胞存活时间更长,倾向于表现出神经元表型,并能增强宿主纤维的芽生。自1987年以来,我们在PD患者中植入灌注后的AM和胎儿腹侧中脑(FVM)已取得了不同程度的临床改善。如果供体组织决定了改善效果,那么不同类型的植入物应会在质量和数量上带来不同程度的改善。本研究的目的是确定接受组织移植(Tx)的PD患者的临床病程、改善斜率以及药物用量的减少是否取决于供体组织类型。在一项初步研究中,4例IV-V级PD患者接受了在尾状核中植入预孵育的自体AM和肋间神经的手术(开放手术)。临床评估基于国际量表(UPD),该量表如之前报道的FVM和灌注AM移植时所使用的那样。未出现全身或神经系统并发症。移植后4年,4例患者的“开”期时间延长,“开”期和“关”期的PD症状(日常生活活动能力和运动性UPD)均有改善,异动症减少。改善似乎是逐步进行的,在移植后数周内开始(类似于AM移植且比我们的FVM移植更早),随后是一段稳定期,在移植后12 - 18个月出现第二波改善(类似于FVM移植),并持续至今。左旋多巴用药量减少了60%以上,且未恢复使用多巴胺激动剂。我们得出结论,我们的接受者在临床上仍比移植前更好。AM和PN联合移植后的恢复过程与FVM或AM移植不同。这一事实可能与产生改善效果的病因学因素有关。