GRAFTED HUMAN INDUCED PLURIPOTENT STEM CELLS IMPROVE THE OUTCOME OF SPINAL CORD INJURY: MODULATION OF THE LESION MICROENVIRONENT
Zsófia Tézsla1,Tamás Bellák1, 2, Zoltán Fekécs1, Dénes Török1, Zsuzsanna Táncos2, Csilla Nemes2,†1, László Gál1, Julianna Kobolák2, András Dinnyés2, 3, 4, Antal Nógrádi1, Krisztián Pajer1
Spinal cord injury results in irreversible tissue damage followed by a very limited recovery of function. In this study we investigated whether transplantation of undifferentiated human induced pluripotent stem cells (hiPSCs) into the injured rat spinal cord is able to induce morphological and functional improvement. hiPSCs were grafted intraspinally or intravenously one week after a thoracic (T11) spinal cord contusion injury performed in Fischer 344 rats. Control animals underwent contusion injury without hiPSC transplantation. Locomotor analysis of the injured animals was performed by the BBB-test and a detailed kinematic analysis system. Two months after the transplantation the retrograde tracer Fast Blue (FB) was applied distally to the injury to determine the extent of axonal sparing/regeneration. Grafted animals showed significantly better functional recovery after contusion injury. Morphologically, the contusion cavity was significantly smaller, and the amount of spared white matter was significantly greater in grafted animals than in controls. Retrograde tracing studies showed a statistically significant increase in the number of FB-labelled neurons in different segments of the spinal cord, the brainstem and the sensorimotor cortex. The extent of regeneration and functional improvement was inversely related to the amount of chondroitin-sulphate around the cavity and the astrocytic and microglial reactions in the injured segment. The grafts produced GDNF, IL-10 and MIP1-alpha in a paracrine fashion for at least one week. These data suggest that grafted undifferentiated hiPSCs are able to induce morphological and functional recovery after spinal cord contusion injury. Funding: No. PIAPP-GA-2012-324451, No. HEALTH-2012-F2-278418; No. 739593; 20391-3/2018/FEKUSTRAT (AD); ÚNKP-19-2 (ZST).