Promotion of spinal cord regeneration by neural stem cell-secreted trimerized cell adhesion molecule L1.
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Promotion of spinal cord regeneration by neural stem cell-secreted trimerized cell adhesion molecule L1. / He, Xiaowen; Knepper, Michael; Ding, Cheng; Li, Jun; Castro, Suita; Siddiqui, Maham; Schachner, Melitta.
in: PLOS ONE, Jahrgang 7, Nr. 9, 9, 2012, S. 46223.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Promotion of spinal cord regeneration by neural stem cell-secreted trimerized cell adhesion molecule L1.
AU - He, Xiaowen
AU - Knepper, Michael
AU - Ding, Cheng
AU - Li, Jun
AU - Castro, Suita
AU - Siddiqui, Maham
AU - Schachner, Melitta
PY - 2012
Y1 - 2012
N2 - The L1 cell adhesion molecule promotes neurite outgrowth and neuronal survival in homophilic and heterophilic interactions and enhances neurite outgrowth and neuronal survival homophilically, i.e. by self binding. We investigated whether exploitation of homophilic and possibly also heterophilic mechanisms of neural stem cells overexpressing the full-length transmembrane L1 and a secreted trimer engineered to express its extracellular domain would be more beneficial for functional recovery of the compression injured spinal cord of adult mice than stem cells overexpressing only full-length L1 or the parental, non-engineered cells. Here we report that stem cells expressing trimeric and full-length L1 are indeed more efficient in promoting locomotor recovery when compared to stem cells overexpressing only full-length L1 or the parental stem cells. The trimer expressing stem cells were also more efficient in reducing glial scar volume and expression of chondroitin sulfates and the chondroitin sulfate proteoglycan NG2. They were also more efficient in enhancing regrowth/sprouting and/or preservation of serotonergic axons, and remyelination and/or myelin sparing. Moreover, degeneration/dying back of corticospinal cord axons was prevented more by the trimer expressing stem cells. These results encourage the view that stem cells engineered to drive the beneficial functions of L1 via homophilic and heterophilic interactions are functionally optimized and may thus be of therapeutic value.
AB - The L1 cell adhesion molecule promotes neurite outgrowth and neuronal survival in homophilic and heterophilic interactions and enhances neurite outgrowth and neuronal survival homophilically, i.e. by self binding. We investigated whether exploitation of homophilic and possibly also heterophilic mechanisms of neural stem cells overexpressing the full-length transmembrane L1 and a secreted trimer engineered to express its extracellular domain would be more beneficial for functional recovery of the compression injured spinal cord of adult mice than stem cells overexpressing only full-length L1 or the parental, non-engineered cells. Here we report that stem cells expressing trimeric and full-length L1 are indeed more efficient in promoting locomotor recovery when compared to stem cells overexpressing only full-length L1 or the parental stem cells. The trimer expressing stem cells were also more efficient in reducing glial scar volume and expression of chondroitin sulfates and the chondroitin sulfate proteoglycan NG2. They were also more efficient in enhancing regrowth/sprouting and/or preservation of serotonergic axons, and remyelination and/or myelin sparing. Moreover, degeneration/dying back of corticospinal cord axons was prevented more by the trimer expressing stem cells. These results encourage the view that stem cells engineered to drive the beneficial functions of L1 via homophilic and heterophilic interactions are functionally optimized and may thus be of therapeutic value.
KW - Animals
KW - Female
KW - Immunohistochemistry
KW - Mice
KW - Blotting, Western
KW - Neural Cell Adhesion Molecule L1/metabolism
KW - Motor Activity/physiology
KW - Spinal Cord Regeneration/physiology
KW - Nerve Regeneration/physiology
KW - Chondroitin Sulfate Proteoglycans/metabolism
KW - Embryonic Stem Cells/metabolism
KW - Neural Stem Cells/metabolism
KW - Spinal Cord Injuries/metabolism
KW - Animals
KW - Female
KW - Immunohistochemistry
KW - Mice
KW - Blotting, Western
KW - Neural Cell Adhesion Molecule L1/metabolism
KW - Motor Activity/physiology
KW - Spinal Cord Regeneration/physiology
KW - Nerve Regeneration/physiology
KW - Chondroitin Sulfate Proteoglycans/metabolism
KW - Embryonic Stem Cells/metabolism
KW - Neural Stem Cells/metabolism
KW - Spinal Cord Injuries/metabolism
U2 - 10.1371/journal.pone.0046223
DO - 10.1371/journal.pone.0046223
M3 - SCORING: Journal article
VL - 7
SP - 46223
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 9
M1 - 9
ER -
