PMID- 25799169 OWN - NLM STAT- MEDLINE DCOM- 20151215 LR - 20181202 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - The effects of secretion factors from umbilical cord derived mesenchymal stem cells on osteogenic differentiation of mesenchymal stem cells. PG - e0120593 LID - 10.1371/journal.pone.0120593 [doi] LID - e0120593 AB - Factors synthesized by mesenchymal stem cells (MSCs) contain various growth factors, cytokines, exosomes and microRNAs, which may affect the differentiation abilities of MSCs. In the present study, we investigated the effects of secretion factors of human umbilical cord derived mesenchymal stem cells (hUCMSCs) on osteogenesis of human bone marrow derived MSCs (hBMSCs). The results showed that 20 mug/ml hUCMSCs secretion factors could initiate osteogenic differentiation of hBMSCs without osteogenic induction medium (OIM), and the amount of calcium deposit (stained by Alizarin Red) was significantly increased after the hUCMSCs secretion factors treatment. Real time quantitative reverse transcription-polymerase chain reaction (real time qRT-PCR) demonstrated that the expression of osteogenesis-related genes including ALP, BMP2, OCN, Osterix, Col1alpha and Runx2 were significantly up-regulated following hUCMSCs secretion factors treatment. In addition, we found that 10 mug hUCMSCs secretion factors together with 2x10(5) hBMSCs in the HA/TCP scaffolds promoted ectopic bone formation in nude mice. Local application of 10 mug hUCMSCs secretion factors with 50 mul 2% hyaluronic acid hydrogel and 1x10(5) rat bone marrow derived MSCs (rBMSCs) also significantly enhanced the bone repair of rat calvarial bone critical defect model at both 4 weeks and 8 weeks. Moreover, the group that received the hUCMSCs secretion factors treatment had more cartilage and bone regeneration in the defect areas than those in the control group. Taken together, these findings suggested that hUCMSCs secretion factors can initiate osteogenesis of bone marrow MSCs and promote bone repair. Our study indicates that hUCMSCs secretion factors may be potential sources for promoting bone regeneration. FAU - Wang, Kui-Xing AU - Wang KX AD - Ministry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China. FAU - Xu, Liang-Liang AU - Xu LL AD - Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Orthopaedics & Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. FAU - Rui, Yun-Feng AU - Rui YF AD - Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Huang, Shuo AU - Huang S AD - Department of Orthopaedics & Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. FAU - Lin, Si-En AU - Lin SE AD - Department of Orthopaedics & Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. FAU - Xiong, Jiang-Hui AU - Xiong JH AD - The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China; State Key Laboratory of Space Medical Fundamentation and Application, Astronaut Research and Training Center of China (ACC), 26 Beiqing Road, 100094, Beijing, China. FAU - Li, Ying-Hui AU - Li YH AD - The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China; State Key Laboratory of Space Medical Fundamentation and Application, Astronaut Research and Training Center of China (ACC), 26 Beiqing Road, 100094, Beijing, China. FAU - Lee, Wayne Yuk-Wai AU - Lee WY AD - Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Orthopaedics & Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. FAU - Li, Gang AU - Li G AD - Ministry of Education Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Orthopaedics & Traumatology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150323 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antigens, Surface) RN - 0 (Biomarkers) SB - IM MH - Animals MH - Antigens, Surface/metabolism MH - *Autocrine Communication MH - Biomarkers MH - Bone Regeneration/drug effects MH - Cell Culture Techniques MH - *Cell Differentiation/drug effects MH - Humans MH - Male MH - Mesenchymal Stem Cells/*cytology/*metabolism MH - Mice MH - Mice, Nude MH - *Osteogenesis/drug effects MH - Phenotype MH - Rats MH - Umbilical Cord/*cytology PMC - PMC4370627 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/03/24 06:00 MHDA- 2015/12/17 06:00 PMCR- 2015/03/23 CRDT- 2015/03/24 06:00 PHST- 2014/10/13 00:00 [received] PHST- 2015/01/24 00:00 [accepted] PHST- 2015/03/24 06:00 [entrez] PHST- 2015/03/24 06:00 [pubmed] PHST- 2015/12/17 06:00 [medline] PHST- 2015/03/23 00:00 [pmc-release] AID - PONE-D-14-39853 [pii] AID - 10.1371/journal.pone.0120593 [doi] PST - epublish SO - PLoS One. 2015 Mar 23;10(3):e0120593. doi: 10.1371/journal.pone.0120593. eCollection 2015.