Brief Report: Astrogliosis Promotes Functional Recovery of Completely Transected Spinal Cord Following Transplantation of hESC-Derived Oligodendrocyte and Motoneuron Progenitors

Authors

  • Dunja Lukovic,

    1. CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, Sevilla, Spain
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  • Lourdes Valdés-Sanchez,

    1. CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, Sevilla, Spain
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  • Irene Sanchez-Vera,

    1. CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, Sevilla, Spain
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  • Victoria Moreno-Manzano,

    1. Neuronal and Tissue Regeneration Lab, Research Center “Principe Felipe”, Valencia, Spain
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  • Miodrag Stojkovic,

    1. Spebo Medical, Leskovac, Serbia
    2. Human Genetics, Faculty of Medical Sciences, Kragujevac, Serbia
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  • Shomi S. Bhattacharya,

    1. CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, Sevilla, Spain
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  • Slaven Erceg

    Corresponding author
    1. CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, Sevilla, Spain
    • Correspondence: Slaven Erceg, Ph.D., CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, 41092 Sevilla, Spain. Telephone: +34 954 468 004; Fax: +34 954 461 664; e-mail: slaven.erceg@cabimer.es

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Abstract

Spinal cord injury results in neural loss and consequently motor and sensory impairment below the injury. Reactive astrocytes contribute to formation of glial scar, thus impeding axonal regeneration, through secretion of extracellular matrix molecules, chondroitin sulfate proteoglycans (CSPGs). In this study, we analyze lesion site tissue to reveal the possible mechanism underlying the functional recovery after cell transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cell (OPC) and motoneuron progenitors (MP) and propose that transplanted cells increase astrogliosis through the regenerative signaling pathways activated in the host tissue that may crucial for restoring locomotor ability. We show that the transplantation of hESC-derived OPC and MP promotes astrogliosis, through activation of Jagged1-dependent Notch and Jak/STAT signaling that support axonal survival. The transplanted cells in synergism with reactive astrocytes create permissive environment in which the expression of detrimental genes (Cspg, Tenascins, and genes involved in SLIT/ROBO signaling) was significantly decreased while expression of beneficial ones (Laminins and Fibronectin) was increased. According to our data, this mechanism is activated in all transplantation groups independently of the level of locomotor recovery. These results indicate that modifying the beneficial function of reactive astrocytes could be a feasible therapeutic strategy for spinal cord injury in future. Stem Cells 2014;32:594–599

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