Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA271

Poster Communications

Comparison between the Functional Restorative Capacity of Adipose Tissue and Bone Marrow Derived Mesenchymal Stem Cells in Cerebellar Ataxic Rat Model

Y. M. ELWAZIR1,2, R. Atta3, N. Abogresha3, A. Ameen3, H. Korayem4

1. Medical Physiology, Suez Canal University, Ismailia, Ismailia, Egypt. 2. Center of Excellence of Cellular & Molecular Medicine, Suez Canal University, Ismailia, Egypt. 3. Medical Physiology, Suez Canal University, Ismailia, Egypt. 4. Histology, Suez Canal University, Ismailia, Egypt.

Cerebellar ataxias represent a group of disabling disorders of balance and coordination. In absence of definitive therapy so far, stem cells can represent the needed hope. The present study compared the therapeutic efficacy of adipose stem cells (ASCs) and bone marrow mesenchymal stem cells (BM-MSCs) in a rat model of cerebellar ataxia. Forty adult female Albino Wistar rats were equally divided into control, MSG, BM-MSCs and ASCs groups. Six additional adult male rats of the same species were used for isolation of retroperitoneal adipose tissue and bone marrow from femur and tibia. After acclimatization, the latter three groups received intraperitoneal (IP) injection of 4 gm/kg body weight of monosodium glutamate (MSG) once daily for 6 days to induce cerebellar ataxia, whereas the control group received 1 ml saline IP for 6 days. On the 7th day, each of the 2 stem cell groups received one million related cell type dissolved in 250 μL PBS, whereas the other 2 groups received only PBS as a single IV injection in tail vein. Motor coordination was assessed weekly afterwards for 4 weeks using rotarod test, open field test and quantitative gait analysis. Then rats were sacrificed, and cerebellum was dissected for histological examination, immunohistochemical analysis of Purkinje cells regeneration and apoptosis using Bax/Bcl-2 ratio, VEGF level, ELISA to detect ILGF-1 and PCR analysis to detect SRY gene expression. Values are means ± SD, compared by ANOVA. Physiological assessment showed significant deterioration in MSG group in all tests all over the study period compared to control group, and significant improvements in both stem cell groups with earlier onset in ADS group. Histological study in MSG group revealed widely displaced, distorted and shrunken Purkinje cells with marked decrease in number of Nissl granules per Purkinje cell (0.223±0.003). In both stem cell groups, there was significant decrease in the number of distorted Purkinje cells with significant increase in number of Nissl granules; 0.35±0.002 in BM-MSC group and 0.51±0.001 in ASC group. There was significant increase in Bax/Bcl-2 ratio in MSG group (2.53±0.06) as compared to BM-MSC group (0.47±0.05) and to ASC group (0.40±0.03). VEGF immunostaining showed a significant increase in the ASC group (46.65±1.22%) as compared to BM-MSCs group (38.70±0.99%), which was also significantly higher than MSG group (24.44±2.14%). Similarly, IGF-1 was significantly higher in ASC group (39.77±2.34 ng\ml) as compared to BM-MSC group (19.32±0.39) and to MSG group (5.93±0.35). SRY gene could not be detected in the cerebellum of female recipients. In conclusion, our study showed that both stem cell types induced structural, physiological and biochemical improvement of cerebellar ataxia, with significantly better results of ASCs therapy.

Where applicable, experiments conform with Society ethical requirements