title: Brief report: astrogliosis promotes functional recovery of completely transected spinal cord following transplantation of hESC-derived oligodendrocyte and motoneuron progenitors.
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.
authors.affiliation: CABIMER (Centro Andaluz de Biología Molecular y Medicina Regenerativa), Avda. Americo Vespucio s/n, Parque Científico y Tecnológico Cartuja, Sevilla, Spain.
authors.forename: Dunja
authors.initials: D
authors.lastname: Lukovic
authors.forename: Lourdes
authors.initials: L
authors.lastname: Valdés-Sanchez
authors.forename: Irene
authors.initials: I
authors.lastname: Sanchez-Vera
authors.forename: Victoria
authors.initials: V
authors.lastname: Moreno-Manzano
authors.forename: Miodrag
authors.initials: M
authors.lastname: Stojkovic
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
authors.forename: Slaven
authors.initials: S
authors.lastname: Erceg
mesh_terms: D001253:Astrocytes / Q000378:metabolism*; D017690:Cell Transplantation; D053595:Embryonic Stem Cells / Q000378:metabolism; D005911:Gliosis / Q000235:genetics*; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D020127:Recovery of Function; D015398:Signal Transduction / Q000235:genetics*; D013119:Spinal Cord Injuries
keywords: Cell transplantation; Cellular therapy; Neural differentiation; Spinal cord injury