Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury.
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.
Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Yu
Y
Zhang
Department of Orthopedics, the Second People's Hospital of Changshu, Suzhou, China.
Jinhua
J
Yang
Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Peng
P
Zhang
Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Tao
T
Liu
Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou Industrial Park, Suzhou, China.
Jianwei
J
Xu
Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Zhihai
Z
Fan
Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Yixin
Y
Shen
Department of Human Anatomy, Medical College of Soochow University, Suzhou Industrial Park, Suzhou, China.
Wenjie
W
Li
Department of Cell Biology, Jiangsu Key Laboratory of Stem Cell Research, Medical College of Soochow University, Suzhou Industrial Park, Suzhou, China.
Huanxiang
H
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*
D047428:Protein Kinase Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D015740:Calcitonin Gene-Related Peptide