Increased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration

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dc.citation.firstpage5039en_US
dc.citation.issueNumber18en_US
dc.citation.journalTitleTheranosticsen_US
dc.citation.lastpage5058en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorLu, Jiajuen_US
dc.contributor.authorShen, Xuezhenen_US
dc.contributor.authorSun, Xunen_US
dc.contributor.authorYin, Heyongen_US
dc.contributor.authorYang, Shuhuien_US
dc.contributor.authorLu, Changfengen_US
dc.contributor.authorWang, Yuen_US
dc.contributor.authorLiu, Yifanen_US
dc.contributor.authorHuang, Yingqien_US
dc.contributor.authorYang, Zijinen_US
dc.contributor.authorDong, Xianqien_US
dc.contributor.authorWang, Chenhaoen_US
dc.contributor.authorGuo, Quanyien_US
dc.contributor.authorZhao, Lingyunen_US
dc.contributor.authorSun, Xiaodanen_US
dc.contributor.authorLu, Shibien_US
dc.contributor.authorMikos, Antonios G.en_US
dc.contributor.authorPeng, Jiangen_US
dc.contributor.authorWang, Xiumeien_US
dc.date.accessioned2019-01-08T15:37:47Zen_US
dc.date.available2019-01-08T15:37:47Zen_US
dc.date.issued2018en_US
dc.description.abstractEven small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration. Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold. Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29+ /CD90+ double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups. Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for clinical application in the future.en_US
dc.identifier.citationLu, Jiaju, Shen, Xuezhen, Sun, Xun, et al.. "Increased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration." <i>Theranostics,</i> 8, no. 18 (2018) Ivyspring: 5039-5058. https://doi.org/10.7150/thno.26981.en_US
dc.identifier.digitalv08p5039en_US
dc.identifier.doihttps://doi.org/10.7150/thno.26981en_US
dc.identifier.urihttps://hdl.handle.net/1911/104984en_US
dc.language.isoengen_US
dc.publisherIvyspringen_US
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_US
dc.subject.keywordacellular cartilage matrixen_US
dc.subject.keywordcartilage regenerationen_US
dc.subject.keywordself-assembling peptide hydrogelen_US
dc.subject.keywordstem cell homingen_US
dc.titleIncreased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regenerationen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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