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Table 1 Summary of study characteristics in animal model

From: Systemic therapy of MSCs in bone regeneration: a systematic review and meta-analysis

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
  1. 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