Utologous cell transplantation in a rabbit model so that long-term results for 6 months to 1 year could be evaluated. The other possible reason for insufficient chondrogenesis may be too much distance between BMSCs and chondrocyte bricks. Different from PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/14960617 direct mixing of cells, gaps between BMSCs and chondrocyte bricks will weaken the paracrine signals released from cell bricks. The size of cell bricks should therefore be optimized further in 1-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole studies so that adequate distribution could be acquired.Conclusion The findings reported here provided a novel, efficient and injectable approach to regenerate cartilage tissues in vivo. Compared with chondrocytes, chondrocyte bricks could maintain the graft morphology in vivo, enable cartilage repair with specific shape, and persistently prevent hypertrophic transition of BMSCs in vivo. On the other hand, BMSCs interacted with cell bricks and mediated early vasculogenesis in the interior of graft, which warranted the survival of interior cells and chondrogenesis of whole grafts.Abbreviations BMSC: bone marrow-derived mesenchymal stem cell; Brdu: 5-bromo-2-deoxy uridine; COL: collagen (gene); DMEM: Dulbecco's modified Eagle's medium; ECM: extracellular matrix; GAG: glycosaminoglycan; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; H E: hematoxylin and eosin; PBS: phosphatebuffered saline; PRP: platelet-rich plasma; sGAG: sulfated glycosaminoglycan; VEGF: vascular endothelial growth factor. Competing interests The authors declare that they have no competing interests. Authors' contributions RKB carried out acquisition of all data and contributed substantially to the analysis and interpretation of the data, drafting and revision of the manuscript. JHW, XBC and ML contributed to data acquisition and journal.pone.0167038 data analysis. YMZ and WW carried out the design and coordination PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9638577 of the study and contributed substantially to drafting and revision of the manuscript critically for important intellectual content. All authors read and approved the final version of the manuscript. Acknowledgements This research was supported by the National Natural Science Foundation of China (Grant No. 81422008/81271104) and the Project of the National Twelfth-Five Year Research Program of China (2012BAI07B02). Received: 28 August 2014 Revised: 24 November 2014 Accepted: 9 February 2015 References 1. Scotti C, Piccinini E, Takizawa H, Todorov A, Bourgine P, Papadimitropoulos A, et al. Engineering of a functional bone organ through endochondral ossification. Proc Natl Acad 3-Fluoro-2-(trifluoromethyl)aniline Sci U S A. 2013;110:3997?002. 2. Gawlitta D, Farrell E, Malda J, Creemers LB, Alblas J, Dhert WJ. Modulating endochondral ossification of multipotent stromal cells for bone regeneration. Tissue Eng Part B Rev. 2010;20:385?5. 3. Bian L, Guvendiren M, Mauck RL, Burdick JA. Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis. Proc Natl Acad Sci U S A. 2013;110:10117?2. 4. Hoemann CD, Sun J, Legare A, McKee MD, Buschmann MD. Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthritis Cartilage. 2005;13:318?9.Ba et al. Stem Cell Research Therapy (2015) 6:Page 14 of5.6.7.8.9.10.11.12. 13.14.15.16.17.18.19. 20.21.22.23.24.25.26.27.Tan H, Chu CR, Payne KA, Marra KG. Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials. 2009;30:2499?06. Pelttari K, Winter A, Steck E, Goetzke K, Hennig T,.