Grafted human induced pluripotent stem cells improve the outcome of spinal cord injury: modulation of the lesion microenvironment

Tamás Bellák,Csilla Nemes,Antal Nógrádi,Julianna Kobolák,Suchitra Polgári,Zsófia Tézsla,Dénes Török,Zoltán Fekécs,Zsuzsanna Táncos,András Dinnyés,László Gál,Krisztián Pajer

doi:10.1038/s41598-020-79846-2

Abstract

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. Grafted animals showed significantly better functional recovery than the control rats which received only contusion injury. Morphologically, the contusion cavity was significantly smaller, and the amount of spared tissue was significantly greater in grafted animals than in controls. Retrograde tracing studies showed a statistically significant increase in the number of FB-labeled neurons in different segments of the spinal cord, the brainstem and the sensorimotor cortex. The extent of 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 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.

Highlights

Spinal cord injury results in irreversible tissue damage followed by a very limited recovery of function
The aim of the present study was to investigate whether transplantation of undifferentiated human induced pluripotent stem cells (hiPSCs) into the injured rat spinal cord may lead to secretion of a set of bioactive molecules—called “lesion induced secretome”— which may support the repair of damaged tissue by modulating the local immune response, enhancing tissue sparing and altering the lesion microenvironment to support axonal regeneration/plasticity
Our study provides strong evidence that intraspinal transplantation of undifferentiated hiPSCs is an effective strategy to induce tissue sparing after Spinal cord injury (SCI)

Summary

Introduction

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. The grafts produced GDNF, IL-10 and MIP1-alpha 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. Based on the properties of the SB5 hiPSC line, we hypothesized that transplantation of these cells into a contused spinal cord may lead to considerable morphological regeneration/ tissue sparing and restoration of function after injury. The aim of the present study was to investigate whether transplantation of undifferentiated hiPSCs into the injured rat spinal cord may lead to secretion of a set of bioactive molecules—called “lesion induced secretome”— which may support the repair of damaged tissue by modulating the local immune response, enhancing tissue sparing and altering the lesion microenvironment to support axonal regeneration/plasticity

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