PMID- 25739039 OWN - NLM STAT- MEDLINE DCOM- 20160108 LR - 20220310 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 12 IP - 1 DP - 2015 Jul TI - Conditioned medium from umbilical cord mesenchymal stem cells induces migration and angiogenesis. PG - 20-30 LID - 10.3892/mmr.2015.3409 [doi] AB - Umbilical cord mesenchymal stem cells (UC-MSCs) have been suggested as a candidate for various clinical applications, however, major limitations include the lack of organ-specific accumulation and low survival rates of transplanted cells. In the present study, it was hypothesized that the paracrine effects of UC‑MSCs may enhance stem cell-based tissue repair and regeneration by promoting the specific homing of stem/progenitor cells and the overall ability to drive them to the damaged area. UC-MSCs-derived conditioned medium (UC-CM) was analyzed using liquid chip and ELISA techniques. In vitro tube formation assays of human umbilical vein endothelial cells (HUVECs) and UC-MSCs were then performed to assess the angiogenic properties of UC-CM. Subsequently, UC-MSCs, HUVECs and fibroblasts were labeled with PKH26 for an in vivo cell migration assay. The expression levels of C-X-C chemokine receptor 4 (CXCR4), C-C chemokine receptor 2 (CCR2) and c-met were determined in the UC-MSCs, HUVECs and fibroblasts using reverse transcription-quantitative polymerase chain reaction and flow cytometry. UC-CM was incubated with or without antibodies, and the contribution of stromal cell-derived factor 1 (SDF-1), monocyte chemotactic protein 1 (MCP-1) and hepatocyte growth factor (HGF) on the migration of cells was investigated in vitro. The results demonstrated that UC-MSCs secreted different cytokines and chemokines, including increased quantities of SDF-1, MCP-1 and HGF, in addition to the angiogenic factors, vascular cell adhesion protein-1, interleukin-8, insulin-like growth factor-1 and vascular endothelial growth factor. The total lengths of the tubes were significantly increased in the UC-MSCs and HUVECs incubated in UC-CM compared with those incubated in Dulbecco's modified Eagle's medium. In vivo cell migration assays demonstrated that UC-CM was a chemotactic stimulus for the UC-MSCs and HUVECs. In vitro Matrigel migration and scratch healing assays demonstrated that UC-CM increased the migration of CXCR4-positive or/and CCR2-positive cells in a dose-dependent manner. In addition, different molecules were screened under antibody-based blocking migration conditions. The data revealed that the SDF-1/CXCR4 and MCP-1/CCR2 axes were involved in the chemoattractive activity of UC-CM and suggested that the effective paracrine factor of UC-CM is a large complex rather than a single factor. The results of the present study supported the hypothesis that UC-MSCs release soluble factors, which may extend the therapeutic applicability of stem cells. FAU - Shen, Chongyang AU - Shen C AD - Key Laboratory of Obstetric, Gynecologic, Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Lie, Puchang AU - Lie P AD - Key Laboratory of Regeneratative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China. FAU - Miao, Tianyu AU - Miao T AD - West China School of Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Yu, Meixing AU - Yu M AD - Key Laboratory of Obstetric, Gynecologic, Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Lu, Qiao AU - Lu Q AD - Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Feng, Ting AU - Feng T AD - Key Laboratory of Obstetric, Gynecologic, Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Li, Jinrong AU - Li J AD - Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Zu, Tingting AU - Zu T AD - Key Laboratory of Obstetric, Gynecologic, Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Liu, Xiaohuan AU - Liu X AD - Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. FAU - Li, Hong AU - Li H AD - Key Laboratory of Obstetric, Gynecologic, Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150304 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (CCL2 protein, human) RN - 0 (CCR2 protein, human) RN - 0 (CXCL12 protein, human) RN - 0 (CXCR4 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CXCL12) RN - 0 (Culture Media, Conditioned) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, CXCR4) SB - IM MH - Cell Movement/*drug effects MH - Chemokine CCL2/metabolism MH - Chemokine CXCL12/metabolism MH - Culture Media, Conditioned/metabolism/*pharmacology MH - Human Umbilical Vein Endothelial Cells MH - Humans MH - Mesenchymal Stem Cells/*metabolism MH - Neovascularization, Physiologic/*drug effects/genetics MH - Receptors, CCR2/metabolism MH - Receptors, CXCR4/metabolism MH - Regeneration/*drug effects MH - Umbilical Cord/metabolism PMC - PMC4438972 EDAT- 2015/03/05 06:00 MHDA- 2016/01/09 06:00 PMCR- 2015/03/04 CRDT- 2015/03/05 06:00 PHST- 2014/04/22 00:00 [received] PHST- 2015/01/30 00:00 [accepted] PHST- 2015/03/05 06:00 [entrez] PHST- 2015/03/05 06:00 [pubmed] PHST- 2016/01/09 06:00 [medline] PHST- 2015/03/04 00:00 [pmc-release] AID - mmr-12-01-0020 [pii] AID - 10.3892/mmr.2015.3409 [doi] PST - ppublish SO - Mol Med Rep. 2015 Jul;12(1):20-30. doi: 10.3892/mmr.2015.3409. Epub 2015 Mar 4.