Role of IGF1R(+) MSCs in modulating neuroplasticity via CXCR4 cross-interaction.

Abstract

To guide the use of human mesenchymal stem cells (MSCs) toward clinical applications, identifying pluripotent-like-markers for selecting MSCs that retain potent self-renewal-ability should be addressed. Here, an insulin-like growth factor 1 receptor (IGF1R)-expressing sub-population in human dental pulp MSCs (hDSCs), displayed multipotent properties. IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to that in 10% fetal calf serum (FCS). Cytokine array showed that hUCS contained higher amount of several growth factors compared to FCS, including IGF-1 and platelet-derived growth factor (PDGF-BB). These cytokines modulates the signaling events in the hDSCs and potentially enhances engraftment upon transplantation. Specifically, a bidirectional cross-talk between IGF1R/IGF1 and CXCR4/SDF-1α signaling pathways in hDSCs, as revealed by interaction of the two receptors and synergistic activation of both signaling pathways. In rat stroke model, animals receiving IGF1R(+) hDSCs transplantation, interaction between IGF1R and CXCR4 was demonstrated to promote neuroplasticity, therefore improving neurological function through increasing glucose metabolic activity, enhancing angiogenesis and anti-inflammatiory effects. Therefore, PDGF in hUCS-culture system contributed to the maintenance of the expression of IGF1R in hDSCs. Furthermore, implantation of IGF1R(+) hDSCs exerted enhanced neuroplasticity via integrating inputs from both CXCR4 and IGF1R signaling pathways.

• Authors: Hsu-Tung Lee, Hao-Teng Chang, Sophie Lee, Chen-Huan Lin, Jia-Rong Fan, Shinn-Zong Lin, Chung Y Hsu, Chia-Hung Hsieh, Woei-Cherng Shyu
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 32595 (09 02 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27586516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• CXCR4 protein, human
• Chemokine CXCL12
• Cytokines
• Proto-Oncogene Proteins c-sis
• Receptors, CXCR4
• Becaplermin
• Insulin-Like Growth Factor I
• Receptor, IGF Type 1
• Glucose

Topics

• Animals
• Anti-Inflammatory Agents (metabolism)
• Apoptosis (drug effects)
• Becaplermin
• Brain Ischemia (complications, physiopathology)
• Cerebrovascular Circulation (drug effects)
• Chemokine CXCL12 (pharmacology)
• Child
• Child, Preschool
• Cytokines (metabolism)
• Dental Pulp (cytology)
• Glucose (metabolism)
• Humans
• Insulin-Like Growth Factor I (pharmacology)
• Male
• Mesenchymal Stem Cells (cytology, drug effects, metabolism)
• Neovascularization, Physiologic (drug effects)
• Nerve Regeneration (drug effects)
• Neurogenesis (drug effects)
• Neuronal Plasticity (drug effects)
• Protein Binding (drug effects)
• Proto-Oncogene Proteins c-sis (pharmacology)
• Rats
• Receptor, IGF Type 1 (metabolism)
• Receptors, CXCR4 (metabolism)
• Recovery of Function (drug effects)
• Stem Cell Transplantation
• Stroke (complications, physiopathology, therapy)
• Umbilical Cord (cytology)