The Significance of SDF-1alpha-CXCR4 Axis in in vivo Angiogenic Ability of Human Periodontal Ligament Stem Cells
Yoon-Kyung Bae1,2,3,9, Gee-Hye Kim4,9, Jae Cheoun Lee5, Byoung-Moo Seo6, Kyeung-Min Joo1,2,3,7, and Gene Lee4,*, and Hyun Nam2,3,8
1Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea, 2Single Cell Network
Research Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea 3Stem Cell and Regenerative Medicine
Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Korea, 4Laboratory of Molecular Genetics,
Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Korea, 5Children’s Dental Center and
CDC Baby Tooth Stem Cell Bank, Seoul 06072, Korea, 6Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul
National University, Seoul 03080, Korea, 7Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine,
Suwon 16419, Korea, 8Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Korea,
9These authors contributed equally to this work.
*Correspondence: genelee@snu.ac.kr (GL); snutaeng@gmail.com (HN)
Received January 11, 2017; Accepted April 29, 2017.; Published online June 14, 2017.
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ABSTRACT
Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like characteristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, alpha- smooth muscle actin, platelet-derived growth factor receptor beta, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HUVECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the SDF-1alpha and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel- like structures. In conclusion, we demonstrated the perivascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular diseases.
Keywords: angiogenesis, mesenchymal stem cells, periodontal
ligament stem cells, perivascular cells, SDF-1alpha-CXCR4 axis


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31 May 2017 Volume 40,
Number 5, pp. 315~378

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