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Title

Brief report: Astrogliosis promotes functional recovery of completely transected spinal cord following transplantation of hESC-derived oligodendrocyte and motoneuron progenitors

AuthorsLukovic, Dunja ; Valdés-Sánchez, María Lourdes; Sánchez-Vera, Irene; Moreno-Manzano, Victoria; Stojkovic, Miodrag; Bhattacharya, Shom Shanker ; Erceg, Slaven
KeywordsCell transplantation
Cellular therapy
Neural differentiation
Spinal cord injury
Issue Date1-Oct-2013
PublisherAlphaMed Press
CitationStem Cells 32(2): 594- 599 (2014)
AbstractSpinal 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
Publisher version (URL)http://dx.doi.org/10.1002/stem.1562
URIhttp://hdl.handle.net/10261/123582
DOI10.1002/stem.1562
Identifiersdoi: 10.1002/stem.1562
issn: 1066-5099
Appears in Collections:(CABIMER) Artículos
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