Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration

Table 1

Cell types	References	Animal model	Carrier/scaffold material/delivery method	Groups	Cell source	Single dose	Transplant number	Time point (W)	Conclusion
BMSCs	Lang Li [70]	Canines (); Full-thickness cartilage defects	HA; Intra-articular injection	(1) HA; (2) BMSCs+HA; (3) Control: saline	Allogeneic		1	28	BMSCs+HA can regenerate articular cartilage better than HA alone.
	Wu et al. [71]	Rabbits (); Osteochondral defect	PBS; Intra-articular injection	(1) BMSCs; (2) PRFr; (3) BMSCs+PRFr; (4) Control: untreated	Autologous		2	12	The BMSCs+PRFr group had better results in histological evaluation and GAG production.
	Barrachina et al. [72]	Equine (); Chemically induced OA	LRS; Intra-articular injection	(1) MSCs-primed+LRS; (2) MSCs-naïve+LRS; (3) Control: LRS	Allogeneic		2	8 and 24	MSCs-primed+LRS improved clinical symptoms and reduced synovial inflammation, but there was no significant difference from the control group.
	Vayas et al. [73]	Rabbits (); Full-thickness cartilage defects	PLGA microspheres dispersed in a pluronic F-127 solution; Intra-articular injection	(1) MF; (2) MSCs; (3) BMP (3); (4) MF-BMP (3); (5) MSCs-BMP (3); (6) BMP (12); (7) MF-BMP (12); (8) MSCs-BMP (12); (9) Control: untreated	Allogeneic		1	12 and 24	Compared with MF, BMP-2 and MSCs repaired articular cartilage defects better and were less invasive.
	Xia et al. [66]	Pigs (); Bilateral medial meniscectomy-induced OA	SPIO nanoparticles; Intra-articular injection	(1) SPIO-BMSCs; (2) Control: untreated	Allogenic		4	11	The treatment effect of the MSC group was not significantly different from that of the control group.
	Jiang et al. [74]	Rats (); Cartilage defect	PCL-PTHF; Cell-scaffold construct implantation	(1) PCL-PTHF with rat tail-derived collagen nanofibers+BMSCs; (2) PCL-PTHF with chondroitin sulfate nanofibers+BMSCs; (3) Control: untreated	Allogenic		1	4 and 8	The PCL-PTHF with rat tail-derived collagen nanofiber group showed better chondrogenesis potential in vitro and in vivo.
ADSCs	Kohli et al. [75]	Athymic nude rats (); Osteochondral defect	Alpha Chondro Shield; Cell-scaffold construct implantation	(1) PA MSCs+Alpha Chondro Shield; (2) CD271^+ MSCs+Alpha Chondro Shield; (3) Control: Alpha Chondro Shield	Xenogeneic (human)		1	3	CD271+ADSCs had a stronger ability to promote cartilage regeneration in vivo.
	Li et al. [55]	Rabbits (); Cartilage defect	AECM scaffold; Cell-scaffold construct implantation	(1) ADSCs+scaffold; (2) CD146^+ ADSCs+scaffold; (3) Scaffold; (4) Positive control: sham-operated; (5) Negative control: untreated	Xenogeneic (human)		1	12 and 24	CD146+ ADSCs promoted better cartilage regeneration than that in the control group.
	Mei et al. [76]	Rats (); ACLT-induced OA	PBS; Intra-articular injection	(1) ADSCs+PBS; (2) Control: PBS	Allogenic		1	8 and 12	ADSCs had anti-inflammatory effects and inhibited articular cartilage degeneration.
	Critchley et al. [77]	Caprine (); Osteochondral defect	3D-printed PCL alginate hydrogel biphasic scaffold; Cell-scaffold construct implantation	(1) The biphasic constructs; (2) Maioregen scaffolds (Finceramica)	Allogenic	ADSCss+ chondrocytes	1	24	The biphasic constructs regenerated hyaline cartilage in vivo.
SMSCs/SFMSCs	Yan et al. [78]	Mice (); Bovine type II collagen-induced OA	PBS; Intra-articular injection	(1) SMSCs+PBS; (2) Control: PBS	Xenogeneic (human)		3	10	SMSCs prevented arthritis development and suppressed immune responses.
	Kondo et al. [79]	Pigs (); Full-thickness osteochondral defects	No carrier or scaffold; MSC aggregate implantation	(1) MSC aggregates; (2) Control: untreated	Autologous		1	4 and 12	Autologous synovial MSC aggregates promoted articular cartilage regeneration in vivo.
	Neybecker et al. [80]	Nude rats (); ACLT-induced OA	Saline; Intra-articular injection	(1) SFMSCs+ saline; (2) Saline; (3) Control: sham + saline	Xenogeneic (human)		2	4 and 8	Xenogenic SFMSCs exerted neither chondroprotection nor inflammation in ACLT-induced OA.
	Li et al. [81]	Rats (); Full-thickness cartilage defects	Hyperbranched poly-PEGDA/HA hydrogel; Injected into the cartilage defect site	(1) AFF-MSCs/hydrogel; (2) Hydrogel; (3) Control: PBS	Xenogeneic (human)		1	4 and 8	The composite material significantly repaired articular cartilage defects.
UCBMSCs/WJMSCs	Zhang et al. [6]	Goats (); Full-thickness cartilage defects	AECM scaffold; Cell-scaffold construct implantation	(1) MSCs+ scaffold; (2) MF	Xenogeneic (human)		1	24 and 36	The cell-scaffold constructs maintained the integrity of subchondral bone and regenerated hyaline cartilage.
	Liu et al. [82]	Rabbits (); Full-thickness cartilage defects	ECM scaffold; Cell-scaffold construct implantation	(1) hWJMSCs-scaffold; (2) hWJMSCs-C-scaffold; (3) Scaffold; (4) Control: untreated	Xenogeneic (human)	NS	1	12, 24, 28, and 64	WJMSC composite ECM scaffold regenerated hyaline cartilage in vivo. Undifferentiated WJMSCs had a better repair effect.
	Xing et al. [83]	Rats (); ACLT and medial meniscectomy-induced OA	HA; Intra-articular injection	(1) HA+MSCs; (2) HA; (3) Control: saline	Xenogeneic (human)		1	6 and 12	At 6 weeks, the therapeutic effect of the HA+MSCs group was significantly better than that of other groups, but there was no significant difference between the groups at 12 weeks.
iPSCs	Rim et al. [84]	Rats (); Full-thickness cartilage defects	hiChondroPellet group: no carrier or scaffold; Transplant directly to the defect site; hiChondrocytes group: PBS; Injected into the cartilage defect site	(1) hiChondroPellet; (2) hiChondrocytes+PBS; (3) Defect control: untreated; (4) Normal control	Xenogeneic (human)	hiChondroPellets or hiChondrocytes	1	8	Both the chondropellets and the chondrocytes derived from iPSCs had therapeutic effects on osteochondral defects.
	Kotaka et al. [25]	Nude rats (); Full-thickness cartilage defects	Atelocollagen; Transplant directly to the defect site by an external magnetic field	(1) Magnetic force+iPS+ atelocollagen; (2) iPS+ atelocollagen; (3) Control: atelocollagen	Xenogeneic (human)		1	4, 6, and 8	The histological score of the treatment group was significantly better than that of the control group.
ESCs/EMSCs	Jiang et al. [60]	Rhesus macaques (); Spontaneous OA	Saline; Intra-articular injection	(1) EMSCs; (2) BMSCs; (3) Control: saline	EMSC group: xenogeneic (human); BMSC group: allogeneic		3	4, 8, 12, 16, 24, and 36	The degrees of joint swelling and imaging examination results in the EMSC group and BMSC group were significantly improved.
	Gibson et al. [85]	Nude rats (); Cartilage defects	No carrier or scaffold; Transplant MSC pellets directly to the defect site	(1) MSC pellets (untreated); (2) MSC pellets (pretreated with BMP-2 and Wnt5a); (3) Control: empty defects	Xenogeneic (human)		1	4 and 8	Cartilage progenitor cell particles derived from hESCs pretreated with BMP-2 and Wnt5a induced hyaline cartilage regeneration in vivo.