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The Pro-Inflammatory Cytokines Expression of Porcine Embryonic Stem Cells Xenotransplanted into the Brain and Spinal Cord in Rats

Chia-Hsin Liao, Yu-Jing Liao, Kuo Yuan, Yu-Chi Yang, Yu-Yu Joyce Ho, Jiunn-Wang Liao, Lih-Ren Chen, Yow-Ling Shiue and Jenn-Rong Yang

In this study, we transplanted green fluorescent protein-expressing porcine embryonic stem (pES/GFP+) cells and their derived cells, D12 neuronal progenitors (D12 NP) and D18 neuronal progenitors (D18 NP), into the brain and spinal cord of Sprague-Dawley (SD) rats to investigate the differences of inflammation after xenotransplantation. On day 3, 7, and 14 after transplantation, we collected the brain and spinal cord tissues to investigate the gene expression of interleukin 1-α and -β (IL-1α and IL-1β), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). One month after transplantation, histopathological changes of the brain and spinal cord were examined by H&E staining. The expression patterns of inflammatory-related factors in the spinal cord were more dramatic than those in the brain. On day 14 after transplantation, only D18 NP significantly elevated the expressions of IL-1α and IL-1β in the brain, but almost all grafted cells evoked the expression of IL-1α, IL-1β, IL-6, and TNF-α in the spinal cord. Following H&E staining, no dramatic histopathological abnormality was revealed, indicating that no acute damage can be observed following the experimental period albeit inflammatory gene expressions were temporarily triggered. Although the gene expression patterns varied during the experimental period, no lethality appeared in the rats after xenotransplantation of pES/GFP+ cells. These indicate that pES/GFP+ cells may be a safe cell resource for future application on regenerative medicine.