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Review
. 2020 Jul;77(13):2543-2563.
doi: 10.1007/s00018-019-03445-2. Epub 2020 Jan 8.

Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering

Naoki Nakayama  1   2 , Azim Pothiawala  3 , John Y Lee  3   4 , Nadine Matthias  3 , Katsutsugu Umeda  3   5 , Bryan K Ang  3   6 , Johnny Huard  7   8 , Yun Huang  9 , Deqiang Sun  9
Affiliations
Review

Human pluripotent stem cell-derived chondroprogenitors for cartilage tissue engineering

Naoki Nakayama et al. Cell Mol Life Sci. 2020 Jul.

Abstract

The cartilage of joints, such as meniscus and articular cartilage, is normally long lasting (i.e., permanent). However, once damaged, especially in large animals and humans, joint cartilage is not spontaneously repaired. Compensating the lack of repair activity by supplying cartilage-(re)forming cells, such as chondrocytes or mesenchymal stromal cells, or by transplanting a piece of normal cartilage, has been the basis of therapy for biological restoration of damaged joint cartilage. Unfortunately, current biological therapies face problems on a number of fronts. The joint cartilage is generated de novo from a specialized cell type, termed a 'joint progenitor' or 'interzone cell' during embryogenesis. Therefore, embryonic chondroprogenitors that mimic the property of joint progenitors might be the best type of cell for regenerating joint cartilage in the adult. Pluripotent stem cells (PSCs) are expected to differentiate in culture into any somatic cell type through processes that mimic embryogenesis, making human (h)PSCs a promising source of embryonic chondroprogenitors. The major research goals toward the clinical application of PSCs in joint cartilage regeneration are to (1) efficiently generate lineage-specific chondroprogenitors from hPSCs, (2) expand the chondroprogenitors to the number needed for therapy without loss of their chondrogenic activity, and (3) direct the in vivo or in vitro differentiation of the chondroprogenitors to articular or meniscal (i.e., permanent) chondrocytes rather than growth plate (i.e., transient) chondrocytes. This review is aimed at providing the current state of research toward meeting these goals. We also include our recent achievement of successful generation of "permanent-like" cartilage from long-term expandable, hPSC-derived ectomesenchymal chondroprogenitors.

Keywords: Differentiation; Endochondral ossification; Expansion; Growth factor; Mesenchymal; Permanent cartilage; Regeneration.

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Figures

Fig. 1
Fig. 1
Specification of germ-layer-specific chondroprogenitors from PSCs. K, Flk1/KDR; P, PDGFRα; TGFβR-I, TGFβ receptor inhibitor; FGFR-I, FGF receptor inhibitor; CHIR, CHIR99021; VE-Cad, vascular endothelial cadherin; CFU-E, erythrocyte colony-forming unit; LNGFR, low affinity nerve growth factor receptor
Fig. 2
Fig. 2
Somitic chondrogenesis from mPSCs [110, 111]. N, N-cadherin; F, Flk1; P, PDGFRα; Exo-Wnt3a, exogenous Wnt3a
Fig. 3
Fig. 3
Long-term expandable ectomesenchymal chondroprogenitors from hPSC-derived neural crest-like progeny [81]. Sb, SB431542; CHIR, CHIR99021; CDH2, N-cadherin
Fig. 4
Fig. 4
Post-transplantational suppression of endochondral ossification of tissue-engineered cartilage generated with hPSC-derived chondroprogenitor cells in vitro in the presence of forskolin [148]. Sb, SB431542; CHIR, CHIR99021
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References

    1. Lotz MK, Kraus VB (2010) New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options. Arthritis Res Ther 12:211 - PMC - PubMed
    1. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol. 2015;11:21–34. - PMC - PubMed
    1. De Bari C, Roelofs AJ. Stem cell-based therapeutic strategies for cartilage defects and osteoarthritis. Curr Opin Pharmacol. 2018;40:74–80. - PubMed
    1. Caplan AI. Mesenchymal stem cells. J Orthop Res. 1991;9:641–650. - PubMed
    1. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–147. - PubMed

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