Table 1.

Summary of study characteristics in animal model

Author/year	Species	Age	Weight	Sex	N	Animal model	Type of MSCs	Cell passage number	Number of cells	Number of cells/kg	The way of administration	Frequency of injection	Time of injection	Treatment duration	Quantification of new bone	Combination treatment	Cellular fate
Li et al., 2019 [38]	SD rats	12w	250–300g	Female	16	Tibia bone defect	BMSCs	N	3 × 104	1–1.2 × 105/kg	Tail vein	Once	At the same time of transplantation	4w 8w	Percentage of new bone area, BV/TV, BMD	Erythropoietin	Homing to the defect areas
Liu et al., 2014 [37]	Beagle dogs	3–4y	8.5–10kg	Female	4	Mandibular defect	BMSCs	P3	3.4–4 × 109	4 × 108/kg	Bone marrow cavity	Once	At the same time of transplantation	6w	Width of new bone region, mineralized bone area percent	N	Homing to the mandibular defect
Wu et al., 2016 [36]	Balb-c mice	6–8w	N	Male	4	Periapical lesion	hDPSCs	P4	2 × 106	N	Tail vein	Once	After 14 days of pulp exposure	14d	BV/TV	Hypoxic preconditioning	Homing to periapical lesion
Xu et al., 2014 [39]	C57BL/6 mice	7w	N	Male	18	Mandibular defect	GMSCs	P5	1 × 106	N	Tail vein	Once	At the same time of transplantation	2/3w	New bone area	N	Homing to the bone defect
Cheung et al., 2013 [49]	SD rats	3m	N	Female	5	Unilateral closed femoral fractures	MSCs	N	4 × 105	N	Left ventricle injection	Once	After 3 days of fracture	1/2/3/4w	Mean average callus width/area, BV/TV	Low intensity pulsed ultrasound	Homing to the fracture site
Huang et al., 2015 [51]	FVB/N mice	8w	25–35g	Male	10	Open transverse femoral fracture	BMSCs	P4-P8	5 × 105	1.4–2 × 107/kg	Left ventricle injection	Once	After 4 days of fracture	5w	BV/TV, mean density of BV	N	Nitially trapped in lungs for about 8–9 days and then gradually redistributed to the fracture site
Jiang et al., 2019 [55]	C57BL/6 mice	6w	N	Female	12	Stabilized femur fracture	BMSCs	N	1 × 105	N	Tail vein	Once	At the same time of transplantation	2w	BMD, BV, Bone bass	Parathyroid hormone 1–34	Homing to bone callus
Myers et al., 2012 [58]	Mice	N	N	N	7	Fracture model	BMSCs	≤P5	1 × 106	N	Tail vein	Once	After fracture	2w	New bone area	Insulin-like growth factor	Homing to the site of injury
Rapp et al., 2015 [56]	C57BL/6 mice	12w	N	Male	6	Fracture model	BMSCs	P4-P6	1 × 106	N	Tail vein	Twice	After 2 h of fracture	21d	BV/TV	N	Recruiting into the evolving fracture callus and the transgene was also detected in the lung, heart, liver and kidneys
Tanriverdi et al., 2020 [53]	Wistar-albino rats	10–12w	300–350g	N	7	Polytrauma model	BMSCs	P3	3–3.5 × 105	1 × 106/kg	IV injection	Twice	After 36 h or 5 days of fracture	21d	areas for bone	N	N
Wang et al., 2018 [54]	C57BL/6 mice	8–10w	N	Male	5	Unilateral transverse femur fracture	BMSCs	P3-P4	1 × 106	N	Tail vein	Once	After 1 or 7 or 14 days of facture	2w/6w	BV/TV, BMD	N	Arriving at a fracture site via the lung
Weaver et al., 2010 [50]	Sprague-dawley rats	6m	N	Male	13	Femur fractures	BMSCs	N	1 × 105	N	Tail vein	Once	Before the first application of axial displacement	10/24/48d	BMD	N	Migrating to the femora
Wilson et al., 2012 [48]	Swine	6m	60–80kg	Male	5	Mandible defect	ADSCs	N	5 × 106	6.25–8.3 × 104/kg	Ear vein	Once	At the same time of transplantation	4w	BMD, BMC	N	Travelling to the site of injury
Yao et al., 2016 [52]	Mice	2m	N	Both	8–16	Closed transverse diaphyseal fracture	ADSCs	N	3 × 105	N	Tail vein	Once	After 1 day of fracture	42d	BMD	LLP2A-Alendronate	Homing to the fracture gaps
Chen et al., 2017 [47]	SD rats	7w	180–220g	Female	10	Osteoporosis	BMSCs	P3	5–6.2 × 105	2.8 × 106/kg	Tail vein	Once	After 2 months of making osteoporosis models	2w	BMD	N	N
An et al., 2013 [46]	Balb-c nude mice	10w	N	Female	8	OVX-induced bone loss	UCB-MSCs	P6-8	4 × 105	N	Tail vein	4 times	After 1, 2, 8, and 9 days of OVX surgery	4w/8w	BMD, BV/TV	N	N
Kiernan et al., 2016 [44]	C57BL/6 mice and BALB/c backcross	N	N	Female	8	Sca-1 knock out (type II osteoporosis)	BMSCs	P1	2 × 106	N	Tail vein	Once	N	6m	BV/TV	N	Detected in the long bones and the majority of donor signal was found in the lungs, liver, and spleen
Kumar et al., 2010 [45]	C57BL/6 mice	6w	N	Female	10	OVX-induced bone loss	BMSCs	P4-8	2 × 106	N	Tail vein	5 times	After 5 consecutive days of surgery	5w/10W/15w	BMD	BMP-2	Homing of the transplanted cells to bone marrow accompanied by reduction in the number of cells homing to other tissues including lung, liver, kidney and lymph node
Li et al., 2013 [57]	Swine	12m	30–40kg	Male	5	Bisphosphonate-Related Jaw Osteonecrosis	BMSCs	N	1 × 106	2.5–3.3 × 104/kg	Ear vein	Once	After 8 weeks of tooth extractions	12w	Mean area of osteoid	N	Homing to bone
Sui et al., 2016 [40]	C57BL/6 mice	12w	20–22g	Female	4	Glucocorticoid-induced osteoporosis	BMSCs	N	1 × 106	4.5–5 × 107/kg	IV injection	Once	After 7 days of GIOP injection	5W	BV/TV,BMD	N	Homing to recipient bone marrow within 24 h postinfusion and engrafted for at least 4 weeks postinfusion
Sui et al., 2018 [41]	C57BL/6 mice	12w	N	Female	5	OVX-induced bone loss	BMSCs	N	1 × 107	N	IV injection	Once	After 4 weeks of surgery	4W	BV/TV	N	Less than 5% of the total gonadectomy marrow area in the first 24 h and declined to only approximately 2% at the end of the observation period
Wang et al., 2020 [42]	C57BL/6 mice and Balb/c mice	N	N	Female	7	OVX-induced bone loss	Uterine stem cell-derived osteoprogenitor cells	N	1 × 105	N	Tail vein	8 times	Once a week up to a total of 8 weeks after ovariectomy surgery	6w	BMD, BV/TV,	N	Homing to the femoral head
Yao et al., 2013 [43]	C57BL/6 mice	2m	N	Female	8–14	OVX-induced bone loss	BMSCs	N	5 × 105	N	IV injection	Once	After 2 weeks of OVX surgery 24-week old or 24-month old mice	6w	BV of LVB	Synthetic peptidomimetic ligand	Homing to bone marrow and bone surface

BMSCs, bone marrow-derived mesenchymal stem cells; BV/TV, bone volume (BV) to tissue volume (TV); BMD, bone mineral density; hDPSCs, human dental pulp stem cells; IV, intravenous; ADSCs, adipose-derived mesenchymal stem cells; BMC, bone mineral content; UCB-MSCs, umbilical cord blood, mesenchymal stem cells; OVX, ovariectomy; LVB, lumbar vertebral body