EditorialStem Cells for Cartilage Regeneration: A Roadmap to the Clinic

Celeste Scotti ,1 Alberto Gobbi,2 Norimasa Nakamura ,3,4 and Giuseppe M. Peretti 5,6

1Novartis Institutes for Biomedical Research, Novartis Pharma AG, 4056 Basel, Switzerland2Orthopaedic Arthroscopic Surgery International (OASI) Bioresearch Foundation, Gobbi Onlus, Milan, Italy3Institute for Medical Science in Sports, Osaka Health Science University, Osaka, Japan4Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan5IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy6Department of Biomedical Sciences for Health, University of Milan, Milan, Italy

Correspondence should be addressed to Celeste Scotti; celeste.scotti@novartis.com

Received 11 March 2018; Accepted 11 March 2018; Published 11 April 2018

Copyright © 2018 Celeste Scotti et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cell therapies for cartilage repair date back to 1987 when thefirst autologous chondrocyte implantation (ACI) procedurewas performed. Since then, more than 30,000 patients havebeen treated with these techniques, which should not beconsidered “experimental” anymore. Over the years, severaltechnical improvements have been implemented, leading toincremental advances in the surgical procedure, as reviewedby Y. Nam et al. However, a predictable, standardized, anddurable regeneration of hyaline cartilage tissue, capable towithstand the mechanical forces acting in the joint andto prevent joint degeneration, remains an unmet medicalneed [1].

In this special issue entitled “Stem Cells for CartilageRegeneration: A Roadmap to the Clinic,” the authorsaddressed several relevant topics, ranging from advancedin vitro and in vivo models to alternative cell sources,including induced pluripotent stem cells (iPS), and fromsmart materials to additional target tissues with high unmetmedical need, such as the trachea or the temporomandibularjoint (TMJ).

A key bottleneck to improved therapies is represented byreliable in vitro and in vivo models, capable to predict theclinical outcome. Strong advances have been made in thisfield, towards the development of high-throughput systemsthat allows testing multiple conditions with reproducible,quick, and affordable methods, and S. Lopa et al. provided acomprehensive review of microfluidics and bioprintingapplications. Another important topic is quality control in

cell therapies, in order to better standardize the clinicaloutcome. K. Shiraishi et al. reported an interesting studyanalysis of mRNA and miRNA correlated with in vivocartilage repair, which may open new avenues for patientstratification and selection, beyond the mere qualitycontrol. Regarding in vivo models, a translational modelcapable to duplicate the challenging clinical scenarios hasyet to be developed. M. LoMonaco et al. reviewed extensivelythis topic, ranging from small to large animal models andproviding critical insights for study planning.

The use of articular chondrocytes as a cell source hasbeen considered a bottleneck to a more robust and repro-ducible regeneration of the articular surface, because oftheir typical age-dependency and interdonor variability inthe cartilage-forming capacity [2]. For this reason, recentresearch focused on alternative cell sources and experimen-tal models in order to overcome the intrinsic limitations ofautologous cell therapies based on articular chondrocytes.J. N. Fisher et al. reviewed recent advances in preclinicaland clinical research on a number of tissue sources of pro-genitor cells for cartilage repair, highlighting pros and consof each of them, with a focus on the potential for clinicaltranslation. K. D. Jorgenson et al. presented a suspensionbioreactor incorporating microcarrier technology for theefficient culture of synovial fluid-derived MSCs, which canpotentially support further research with this cell source.Infrapatellar fat pad-derived cells gained attention becauseof their easy accessibility and chondrogenic potential.

HindawiStem Cells InternationalVolume 2018, Article ID 7348560, 2 pageshttps://doi.org/10.1155/2018/7348560

J. F. C. do Amaral et al. reviewed the potential of infrapatellarfat pad cells, discussing their potential for cartilage repair andthe ontogeny relationship with other joint-derived cells andconcluding with some perspective for translational trialsusing this cell source. Another cell type that showedpromising preclinical data, with also a clinical trial ongoing,is synovial MSC [3]. Y. Ikeda et al. reported a successfulapproach to improve further the chondrogenic activity ofsynovial MSC, without the upregulation of hypertrophicand osteogenic genes, by enhanced IGF-1 expression. Last,human-induced pluripotent stem cells (hiPSCs) gained a lotof attention in the last decade, representing a new hope forseveral life-threatening and incurable diseases. Y. A. Rimet al. reported a relevant analysis of the chondrogenicpotential among hiPSCs from different tissues: the findingthat cord blood mononuclear cells represent a better sourcemay support further research in this direction.

Biomaterials are a mainstay of regenerative medicine,especially for articular cartilage. However, it is still a matterof controversy whether a scaffold is strictly needed or not.In this special issue, both approaches are reported. Interest-ingly, F. Hached et al. reported the positive impact of apolysaccharide hydrogel on encapsulated MSCs, with respectto cell viability and ability to secrete potentially therapeuticfactors. Regarding scaffold-free approaches, M. P. Stuartet al. reported a valuable method to engineer spheroids byusing a micromolded nonadhesive hydrogel, without theuse of growth factors.

In this special issue, the authors addressed a series oftopics of relevance for the successful translation of preclinicalapproaches. Cell sources, biomaterials, animal models, andcell manufacturing are all critical factors for cartilage repair,which require additional work to pave the way to the nextgeneration of regenerative therapies, possibly capable torestore durably both joint surface and function in patientsin need.

Celeste ScottiAlberto Gobbi

Norimasa NakamuraGiuseppe M. Peretti

References

[1] C. Scotti, A. Gobbi, G. Karnatzikos et al., “Cartilage repair in theinflamed joint: considerations for biological augmentationtoward tissue regeneration,” Tissue Engineering Part B, Reviews,vol. 22, no. 2, pp. 149–159, 2016.

[2] K. Pelttari, B. Pippenger, M. Mumme et al., “Adult humanneural crest-derived cells for articular cartilage repair,” ScienceTranslation Medicine, vol. 6, no. 251, article 251ra119, 2014.

[3] K. Shimomura, W. Ando, Y. Moriguchi et al., “Next generationmesenchymal stem cell (MSC)–based cartilage repair usingscaffold-free tissue engineered constructs generated with syno-vial mesenchymal stem cells,” Cartilage, vol. 6, Supplement 2,pp. 13S–29S, 2015.

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