Biological property of microencapsulating material in treatment of Parkinson disease with encapsulated PC12 cell

Ying XIONG; Wei WANG; Weiting YU; Xin GUO; Qiuyan WANG; Guohua HU; Yueping SONG; Xiaojun MA

ABSTRACT

BACKGROUND:

Parkinson disease(PD) is a series of clinical symptom induced by decreased dopamine (DA) in the striatum due to nigral dopaminergic neuronal degeneration. The intracerebral transplantation of secretory DA can reverse or improve the symptoms to a certain extent, but immunologic rejection is still existed.

OBJECTIVE:

To probe into cell transplantation with immunoisolation in treatment of in rats without application of immunosuppress and observe its mechanical intensity and the biocompatibility of microcapsule .

DESIGN:

Randomized controlled experiment was designed.

SETTING:

Biomedical Material Engineering Group, Dalian Institute of ChemicalPhysics , Chinese Academy of Sciences, and Department of Neurology, Second Hospital of Jilin University.MATERIALS The experiment was performed in Animal Experimental Center of Second Hospital of Jilin University from August 2003 to February 2004, in which, 40 male Wistar rats were employed. PC12 cell was provided from Shanghai Institute of Cellular Biology of Chinese Academy of Sciences.

METHODS:

6-hydroxydopamine solution was infused in the striatum to prepare animal model of Parkinson disease. Twenty-five rats of those had been prepared successfully and were randomized into microencapsulated cell transplantation group (12 rats), in which, 25 μL cell-loading sodium alginate-chitosan-solium alginate(ACA)microencapsul suspension (equal to 2.5×104 cells) was injected stereotaxically on two points of the right (affected side) striatum of animal model; non-microencapsulated cell transplantation group (7 rats), in which, 25 μL PC12 cell suspension (equal to 5×104cells) was injected; and empty microcapsul transplantation group (6 rats),in which, 25 μL empty microcapsules suspension was injected . On the 7th day after transplantation, in every group, apomorphine (APO) prepared with saline solution was injected (0.05 mg/kg) subcutaneously in the neck; afterwards, the revolving behavior was recorded for each rat, once per week,totally for 12 weeks. In the 12th week after operation, the rats were sacrificed with anesthesia. The brain tissue was collected for pathological observation and microcapsule were retrieved to evaluation of biocompatibility and immunoisolation.numbers before and after transplantation of each group.

RESULTS:

Twenty-five rats entered result analysis and the rest was sule the retrieved ACA microcapsule was integrative in morphology,munoisolation of microcapsule microencapsuled PC12 cells were prolifercycles before and after transplantation of each group the records of lateral revolving of rats in every group before transplantation were not significantly different (P ＞ 0.05). In microencapsuled cell transplantation group, 2weeks later, the average number of revolving was significantly lower than that before the transplantation, or even the revolving stopped; the improved symptoms were maintained till the 12th week after transplantation. In nonmicroencapsulated cell transplantation group, the average revolving number was also significantly lower than that before the transplantation, but that on the 8th and 12th weeks was in tendency of increase, without obvious change compared with that before the transplantation (P ＞ 0.05). The revolving number before and after transplantation in non-microencapsulated transplantation group was similar[(10.5±1.4), (10.5±1.3) cyclos/min, P ＞ 0.05].microcapsule provides immune protection. The grafted encapsulated PC12cells survive for along term in the brain of rats with PD, maintain continuously the normal physiological function and improve the symptoms of PD by synthesizing and releasing DA.