Table 3.

Overview of successful and fundamental pre-clinical studies that outline the safety and efficacy of BM-MSCs intra-articular injections (organised by animal model)

References	Animal model	Cell donor	Sample size	Severity of knee OA	BM-MSC dosage	Outcomes
Al Faqeh et al. [29]	Sheep	Autologous (chondrogenic-induced)	n = 51	Surgically induced (monitored for 24 h) 3-weeks post: Sheep ran 100 m on hard surface daily for 3 weeks	1 Injection: 2 × 106 suspended in 10% foetal bovine serum	Meniscal regeneration and retardation of the progression of OA
Diekman et al. [28]	Mouse	Autologous (purified)	n = 11	Surgically induced: closed tibial plateau fracture	1 Injection: Experimental group: 1 × 105 cells in 6 µl saline Control group: sterile saline solution	Efficacy in preventing OA
Murphy et al. [32]	Goat	Autologous	n = 24	Surgically induced: 3-weeks post: Sheep ran on 90 m hard surface daily for 3 weeks	1 Injection: Experimental group: 10 × 106 suspended in 10% foetal bovine serum Control group: injection of hyaluronan acid (HA)	Meniscal regeneration and retardation of progressive destruction
Lee et al. [31]	Pig	Autologous	n = 27	Surgically induced	1 Injection: Group 1: MSCs with HA Group 2: HA Group 3: Saline solution	Cartilage repair
Gupta et al. [30]	Rat	Xenogeneic (human)	n = 74	Monoiodoacetate (MIA)-induced model of OA	1 Injection: Group 1: sham control received 60 μl of Plasmalyte A Group 2: vehicle control received 60 μl of Plasmalyte A Group 3: 30 μl of HA and 30 μl of vehicle 2 Injections: Group 4: 6 × 105 of Stempeucel® and 30 μl of HA Group 5: 1.3 × 106 of Stempeucel® and 30 μl of HA	Elicited pain reduction and cartilage regeneration
Suhaeb et al. [33]	Rat	Allogenic	n = 36	MIA injection	1 Injection: Control: No treatment Experimental group 1: 25 μl of HA Experimental group 2: 3–5 × 106 cells Experimental group 3: 3–5 × 106 cells + 25 μl of HA	Effective reduction of OA progression alone, compared with combined use of HA and BM-MSCs
Chiang et al. [27]	Rabbit	Allogenic	n = 2	ACLT	1 Injection: Group 1: OA induction without treatment Group 2: Sham operation Group 3: 0.4 mL of HA Group 4: 1 × 106 and 0.4 mL of HA	Reduced OA progression