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.firstpage5039
dc.citation.issueNumber18
dc.citation.journalTitleTheranostics
dc.citation.lastpage5058
dc.citation.volumeNumber8
dc.contributor.authorLu, Jiaju
dc.contributor.authorShen, Xuezhen
dc.contributor.authorSun, Xun
dc.contributor.authorYin, Heyong
dc.contributor.authorYang, Shuhui
dc.contributor.authorLu, Changfeng
dc.contributor.authorWang, Yu
dc.contributor.authorLiu, Yifan
dc.contributor.authorHuang, Yingqi
dc.contributor.authorYang, Zijin
dc.contributor.authorDong, Xianqi
dc.contributor.authorWang, Chenhao
dc.contributor.authorGuo, Quanyi
dc.contributor.authorZhao, Lingyun
dc.contributor.authorSun, Xiaodan
dc.contributor.authorLu, Shibi
dc.contributor.authorMikos, Antonios G.
dc.contributor.authorPeng, Jiang
dc.contributor.authorWang, Xiumei
dc.date.accessioned2019-01-08T15:37:47Z
dc.date.available2019-01-08T15:37:47Z
dc.date.issued2018
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.
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.
dc.identifier.digitalv08p5039
dc.identifier.doihttps://doi.org/10.7150/thno.26981
dc.identifier.urihttps://hdl.handle.net/1911/104984
dc.language.isoeng
dc.publisherIvyspring
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/).
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subject.keywordacellular cartilage matrix
dc.subject.keywordcartilage regeneration
dc.subject.keywordself-assembling peptide hydrogel
dc.subject.keywordstem cell homing
dc.titleIncreased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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