Articular cartilage regeneration: The role of endogenous mesenchymal stem/progenitor cell recruitment and migration

Objective Recent studies have implicated the cyclin dependent kinase inhibitor, p21, in enhanced tissue regeneration observed in MRL/MpJ “super-healer” mice. Specifically, p21 is downregulated in MRL cells and similar ear hole closure to MRL mice has been observed in p21−/− mice. However, the direct implications of p21 deletion in endogenous articular cartilage regeneration remain unknown. In this study, we investigated the role of p21 deletion in the ability of mice to heal full-thickness cartilage defects (FTCDs). Design C57BL/6 and p21−/− ( Cdkn1atm1Tyj) mice were subjected to FTCD and assessment of cartilage healing was performed at 1 hour, 3 days, 1 week, 2 weeks, and 4 weeks post-FTCD using a 14-point histological scoring system. X-ray microscopy was used to quantify cartilage healing parameters (e.g., cartilage thickness, surface area/volume) between C57BL/6 and p21−/− mice. Results Absence of p21 resulted in increased spontaneous articular cartilage regeneration by 3 days post-FTCD. Furthermore, p21−/− mice presented with increased cartilage thickness at 1 and 2 weeks post-FTCD compared with uninjured controls, returning to baseline by 4 weeks post-FTCD. Conclusions We report that p21−/− mice display enhanced articular cartilage regeneration post-FTCD compared with C57BL/6 mice. Furthermore, cartilage thickness was increased in p21−/− mice at 1 week post-FTCD compared with uninjured p21−/− mice and C57BL/6 mice.

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Endogenous cell recruitment strategy for articular cartilage regeneration

Acta Biomaterialia ◽

10.1016/j.actbio.2020.07.008 ◽

2020 ◽

Vol 114 ◽

pp. 31-52

Author(s):

Zhen Yang ◽

Hao Li ◽

Zhiguo Yuan ◽

Liwei Fu ◽

Shuangpeng Jiang ◽

...

Keyword(s):

Articular Cartilage ◽

Cartilage Regeneration ◽

Recruitment Strategy ◽

Cell Recruitment ◽

Articular Cartilage Regeneration

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Biofunctionalized Structure and Ingredient Mimicking Scaffolds Achieving Recruitment and Chondrogenesis for Staged Cartilage Regeneration

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.655440 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhen Yang ◽

Hao Li ◽

Yue Tian ◽

Liwei Fu ◽

Cangjian Gao ◽

...

Keyword(s):

Articular Cartilage ◽

Growth Factor ◽

Chondrogenic Differentiation ◽

Cartilage Regeneration ◽

Recruitment Strategy ◽

Prolonged Release ◽

Cell Recruitment ◽

Articular Cartilage Regeneration

It remains scientifically challenging to regenerate injured cartilage in orthopedics. Recently, an endogenous cell recruitment strategy based on a combination of acellular scaffolds and chemoattractants to specifically and effectively recruit host cells and promote chondrogenic differentiation has brought new hope for in situ articular cartilage regeneration. In this study, a transforming growth factor-β3 (TGF-β3)-loaded biomimetic natural scaffold based on demineralized cancellous bone (DCB) and acellular cartilage extracellular matrix (ECM) was developed and found to improve chondral repair by enhancing cell migration and chondrogenesis. The DCB/ECM scaffold has porous microstructures (pore size: 67.76 ± 8.95 μm; porosity: 71.04 ± 1.62%), allowing the prolonged release of TGF-β3 (up to 50% after 42 days in vitro) and infrapatellar fat pad adipose-derived stem cells (IPFSCs) that maintain high cell viability (>96%) and favorable cell distribution and phenotype after seeding onto the DCB/ECM scaffold. The DCB/ECM scaffold itself can also provide a sustained release system to effectively promote IPFSC migration (nearly twofold in vitro). Moreover, TGF-β3 loaded on scaffolds showed enhanced chondrogenic differentiation (such as collagen II, ACAN, and SOX9) of IPFSCs after 3 weeks of culture. After implanting the composite scaffold into the knee joints of rabbits, enhanced chondrogenic differentiation was discovered at 1, 2, and 4 weeks post-surgery, and improved repair of cartilage defects in terms of biochemical, biomechanical, radiological, and histological results was identified at 3 and 6 months post-implantation. To conclude, our study demonstrates that the growth factor (GF)-loaded scaffold can facilitate cell homing, migration, and chondrogenic differentiation and promote the reconstructive effects of in vivo cartilage formation, revealing that this staged regeneration strategy combined with endogenous cell recruitment and pro-chondrogenesis is promising for in situ articular cartilage regeneration.

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Faculty Opinions recommendation of Adipose-derived stem cells in articular cartilage regeneration: current concepts and optimization strategies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732328799.793562280 ◽

2019 ◽

Author(s):

Francisco Arroyo ◽

José Tapia Ramírez

Keyword(s):

Stem Cells ◽

Articular Cartilage ◽

Cartilage Regeneration ◽

Adipose Derived Stem Cells ◽

Articular Cartilage Regeneration

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Materials for Articular Cartilage Regeneration

Recent Patents on Biomedical Engineering ◽

10.2174/1874764711205030187 ◽

2012 ◽

Vol 5 (3) ◽

pp. 187-199 ◽

Cited By ~ 2

Author(s):

Aysegul Tombuloglu ◽

Ayse B. Tekinay ◽

Mustafa O. Guler

Keyword(s):

Articular Cartilage ◽

Cartilage Regeneration ◽

Articular Cartilage Regeneration

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Articular cartilage regeneration of the knee joint after proximal tibial valgus osteotomy: a prospective study of different intra- and extra-articular operative techniques

Knee Surgery Sports Traumatology Arthroscopy ◽

10.1007/s001670050117 ◽

1999 ◽

Vol 7 (1) ◽

pp. 29-36 ◽

Cited By ~ 35

Author(s):

W. Schultz ◽

Dietmar Göbel

Keyword(s):

Articular Cartilage ◽

Knee Joint ◽

Prospective Study ◽

Cartilage Regeneration ◽

Valgus Osteotomy ◽

Operative Techniques ◽

A Prospective Study ◽

Tibial Valgus ◽

Articular Cartilage Regeneration

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The Effect of Supramalleolar Osteotomy without Marrow Stimulation on Cartilage Regeneration for Medial Compartment Ankle Osteoarthritis: Second-Look Arthroscopic Evaluation of Cartilage Regeneration

Foot & Ankle Orthopaedics ◽

10.1177/2473011420s00054 ◽

2020 ◽

Vol 5 (4) ◽

pp. 2473011420S0005

Author(s):

Jung-Won Lim ◽

Hong-Geun Jung

Keyword(s):

Patient Satisfaction ◽

Articular Cartilage ◽

Cartilage Regeneration ◽

Ankle Arthroscopy ◽

Medial Compartment ◽

Ankle Osteoarthritis ◽

Second Look ◽

The Mean ◽

Surface Angle ◽

Articular Cartilage Regeneration

Category: Ankle Arthritis; Ankle; Arthroscopy Introduction/Purpose: The effect of supramalleolar osteotomy (SMO) without an additional bone marrow-stimulating procedure (BMSP) on articular cartilage regeneration in ankle joint still remains unknown. This study aimed to investigate whether SMO yielded favorable clinical and radiologic outcomes, and to evaluate whether the regeneration of articular cartilage could be observed after SMO without BMSP by second-look arthroscopy. Methods: 43 ankles after SMO (mean follow-up: 35.5 months) were retrospectively reviewed. Visual analog scale (VAS) pain score, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, patient satisfaction were used for functional evaluations. The tibial anterior surface angle (TAS) and tibial lateral surface angle (TLS) were measured on radiographs, and ankle osteoarthritis was classified by Takakura stage. Among the 43 patients, 31 underwent ankle arthroscopy prior to SMO, and second-look arthroscopy was performed at 1-year postoperatively. Tibiotalar cartilage regeneration was evaluated according to the modified Outerbridge classification for the 29 patients who had undergone SMO without BMSP. Results: The mean VAS score and AOFAS score significantly improved from 6.4 preoperatively to 1.4 postoperatively and from 61.1 preoperatively to 88.4 postoperatively, respectively (P < 0.05). Regarding overall postoperative patient satisfaction, 18 (41.8%) patients reported their satisfaction as excellent, 23 (53.5%) as satisfied. The mean TAS and TLS significantly improved from 83.8° and 94.8° preoperatively to 78.4° and 82.2° postoperatively, respectively (P < 0.05). 23 out of 28 preoperative Takakura stage IIIa cases and 3 out of 7 IIIb cases improved to postoperative stage II. On second-look arthroscopy, cartilage regeneration of the medial compartment of the tibiotalar joint was observed in 26 of 29 patients (89.7%), whereas cartilage deterioration was not observed in any patient. Conclusion: Medial tibio-talar articular cartilage regeneration was observed in most cases (89.7%) of medial compartment ankle osteoarthritis after SMO without BMSP, which was confirmed with second-look arthroscopic evaluation. It also showed satisfactory clinical and radiologic outcomes with high patient satisfaction.

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