Head to Knee: Cranial Neural Crest-Derived Cells as Promising Candidates for Human Cartilage Repair

Table 1

(a)

Nasal chondrocytes
Author	Cell types	Experiment type	Culture duration before implantation	Site of transplantation	Scaffold	Main results
Vinatier et al. (2009) [67]	Autologous nasal chondrocytes; Rabbit	In vitro; In vivo	4 weeks in vitro; 6 weeks in vivo	Knee; Rabbit	Si-HPMC hydrogel	Neocartilage: same histological aspect as healthy articular cartilage; Analysis of col type II: hyaline-like cartilage
Fulco et al. (2014) [70]	Autologous nasal chondrocytes; Human	Clinical trial	4 weeks; In vitro; 6 months; Biopsy	Alar lobule; Human	Collagen type I/III scaffold	Reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule stability and functionality of the grafts
Pelttari et al. (2014) [69]	Autologous nasal chondrocytes and articular chondrocytes; Goat	In vitro; In vivo	In vitro: 2 weeks; In vivo: 5 weeks: cell plasticity; 3 and 6 months: preclinical effectiveness	Knee; Goat	Collagen type I/III scaffold	In vitro: nasal chondrocytes: more efficient chondrogenic differentiation than articular chondrocytes (cloning and subcloning); In vivo: nasal chondrocytes gave a higher cartilage repair tissue quality than articular chondrocytes
	Nasal chondrocytes (); Human	In vivo	In vitro: 1 week; In vivo: 5 weeks	Subcutaneous; Nude mice	Collagen type I/III scaffold	Stability of Hox gene expression
	Nasal chondrocytes (septum); Human	Clinical trial; Phase 1	4 weeks before implantation	Traumatic injury; Knee; Human	Collagen type I/III scaffold	(1) No systemic or local adverse events for follow-up patients to 18 months after implantation; (2) Filling of the defect and no graft delamination, with strong reduction of subchondral bone edema 4 months after surgery
Mumme et al. (2016) [68]	Autologous nasal chondrocytes; Autologous articular chondrocytes; Goat	In vivo	In vivo; 4-5 weeks cast; 3-6 months	Knee; Goat	Collagen type I and type III membrane (chondro-Gide)	Typical structures of articular cartilage with nasal chondrocytes. Efficient integration of the grafted tissues with the adjacent native cartilage and underlying subchondral bone with nasal chondrocytes; No sign of osteoarthritis following the graft with nasal chondrocytes as compared to articular chondrocytes
Mumme et al. (2016) [71]	Autologous nasal chondrocytes; Human	Clinical trial	24-month follow-up	Knee; Human	Collagen type I/III scaffold	No adverse reactions; Self-assessed clinical scores for pain, knee function, and quality of life were significantly improved; Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of a native hyaline-like cartilage
	Nude mice	In vivo (tumorigenic tests)	8 weeks	Subcutaneous pockets	Collagen type I/III scaffold	Tumor-free tissues; All explanted organs appeared macroscopically normal and no evidence of tumor formation was observed histologically

(b)

NC-MSC
Author	Cell types	Experiment type	Culture duration	Site of transplantation	Scaffold	Main results
Pierdormenico et al. (2006) [90]	DPSC (human); BM-MSC	In vitro	3-4 weeks	/	/	Failure of chondrogenic differentiation
Iohara et al. (2006) [91]	DPSC (SP) (porcin)	In vitro	45 days	/	/	Almost 30% of SP cells were converted into chondrocytes
Alge et al. (2010) [87]	DPSC (rat); BM-MSC (mouse)	In vitro	3 weeks	/	/	Both DPSC and BM-MSC achieved successful chondrogenic differentiation
Dai et al. (2012) [93]	DPSC+CC; (human)	In vitro; In vivo	/	Nude mice; 8 weeks; Subcutaneous	PGA	FGF9 enhanced chondrogenesis of DPSCs; FGF9 inhibited hypertrophy and ossification in chondrodifferentiated DPSCs
Hsu et al. (2012) [95]	GF; GSC (human)	In vitro	/	/	Chitosan	GSC isolation and culture on chitosan membranes increase their chondrogenic potential
Choi et al. (2013) [106]	PDLSC (human)	In vitro	14 days	/	/	TGF-β1 and BMP-6 stimulate chondrogenic differentiation of PDLSC; If used together they may induce mineralization and hypertrophy
Moshaverinia et al. (2013) [96]	GSC; PDLSC vs. BM-MSC (human)	In vitro; In vivo	4 weeks	Nude mice; Dorsal surface; Subcutaneous	RGD-coupled alginate with high guluronic acid content	PDLSCs showed higher amounts of chondrogenesis and Sox9 and Coll II gene expression than BM-MSCs and GSCs in vitro and in vivo
Rizk et al. (2013) [92]	DPSC (human)	In vitro; In vivo	/	Nude mice; 12 weeks; Lateral side	PLLA/PEG	TGF-β3 increases the chondrogenic potential of DPSC
Yang et al. (2013) [89]	PDLSC GSC (human)	In vitro	8 weeks	/	/	PDLSC had more chondrogenic differentiation potential than GSC
Ferré et al. (2014) [94]	GSC	In vitro	5 weeks	/	/	GSC in chondrogenic differentiation medium showed SOX9-dependent differentiation to both chondrocyte and synoviocyte lineages GSC in 3-week old medium: synovial cells peripheral positive to CAD-11
Nemeth et al. (2014) [107]	DPSC (mouse)	In vitro	/	10-21 days	PEG-GelMA-HA	Nanotopography and HA provide important cues for promoting chondrogenic differentiation of DPSCs
Yeh et al. (2014) [98]	Porcine; Chondrocytes; Human MSC: BM-MSC, AD-MSC, GF, PL-MSC	In vitro; In vivo	3 weeks	NODScid mice; Subcutaneous	CII-HA; SIS	SIS scaffold more suitable for chondrogenic differentiation for all cell types. GF gave the best rate of chondrogenic differentiation on SIS scaffold
Umeda et al. (2015) [104]	IPSC (human); CD271+PDGFRa+CD73+ from the PAX3/SOX10/FOXD3-	In vitro; In vivo	12 weeks	Dorsal skin; NODScid/NSG mice	Gelfoam	The ectomesenchymal cells were expandable without loss of chondrogenic potential for at least 16 passages; TGF-β3 promotes efficiently of these cells to form translucent cartilage particles, which were completely mineralized in 12 weeks in NODScid/NSG mice
Chijimatsu et al. (2017) [105]	Neural crest-derived mesenchymal stem cells from IPSC (iNCMSC)	In vitro; In vivo	7 weeks	Osteochondral defect in euthymic nude rats	/	TGF-β3 alone in chondrogenic medium is not enough to ensure chondrogenic differentiation. BMP2 is required; In vivo, chondrogenic particles failed to restore osteochondral defect contrary to BM-MSC