Abstract
Mesenchymal stem cells (MSCs) can be used to treat many diseases, including spinal cord injury (SCI). Treatment relies mostly on the precise navigation of cells to the injury site for rebuilding the damaged spinal cord. However, the key factors guiding MSCs to the epicenter of SCI remain unknown. Here, we demonstrated that calcitonin gene-related peptide (CGRP), a neural peptide synthesized in spinal cord, can dramatically aid the homing of human umbilical cord mesenchymal stem cells (HUMSCs) in spinal cord-transected SCI rats. First, HUMSCs exhibited chemotactic responses in vitro to CGRP. By time-lapse video analysis, increased chemotactic index (CMI), forward migration index (FMI) and speed contributed to this observed migration. Then, through enzyme immunoassay, higher CGRP concentrations at the lesion site were observed after injury. The release of CGRP directed HUMSCs to the injury site, which was suppressed by CGRP 8–37, a CGRP antagonist. We also verified that the PI3K/Akt and p38MAPK signaling pathways played a critical role in the CGRP-induced chemotactic migration of HUMSCs. Collectively, our data reveal that CGRP is a key chemokine that helps HUMSCs migrate to the lesion site and thereby can be used as a model molecule to study MSCs homing after SCI.
Highlights
Receptor to initiate intracellular signaling[22,23]
To visualize the migratory behavior of a single human umbilical cord mesenchymal stem cells (HUMSCs) responding to CGRP and to determine the migratory responses, including the movement tracks, direction (CMI), efficiency (FMI) and migration speed, we used a Dunn chemotaxis chamber[33]
10−6 mol/L was an efficient concentration of CGRP for studying ex vivo HUMSC migration
Summary
Receptor to initiate intracellular signaling[22,23]. Following tissue injury, such as SCI, increased CGRP participates in vasodilation, sensory transmission, immune modulation and nerve regeneration[24,25,26,27,28]. CGRP, at concentrations ranging from [10−9] to 10−6 mol/L, was added to the lower chamber, and cells that migrated trans-filter to the bottom surface of the membrane were counted.
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