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Table 2 Results of studies

From: Effectiveness of mesenchymal stem cell-conditioned medium in bone regeneration in animal and human models: a systematic review and meta-analysis

Author and yearOutcomeMSC-CM (n)Comparison(n)Control (n)TimeConclusions
(Ando et al.,2014)% of new bone callus in the distraction gapMSC-CM 62% (10)FB-CM: 37%(10)DMEM: 32% (10)15 daysMSC-CM accelerates the formation of new bone callus, shortening the period required for DO treatment
(Chang et al.,2015)% of new bone formation over the total area of the defectHCM:NCNCM: NC__56 daysBone repair is significantly increased with hypoxic MSC-CM by enhancement of endogenous MSCs migration and adhesion and gene regulation by miRNA
(Furuta et al.,2016)Bone union presence of bridging callus on two corticesMSC-CM (9): NCExosomes (9): NCPBS (15): NC6 weeksMSC-derived exosomes rescued the retardation of fracture healing in CD9 −/− mice
(Inukai et al.,2013)Bone regeneration areaMSC-CM /Scaffold: 4.89 ± 1.08 mm2 (6)PBS/ Scaffold: 2,4 mm2 (6)No implant/Scaffold: 1,8 mm2 (6)4 weeksLarge amount of bone and cement formation was observed in the MSC-CM group. There was minimal inflammatory cell infiltration in the MSC-CM
(Katagiri et al.,2013)% area of newly regenerated bone over the total area of the defectMSC-CM (81.50% + −2.7%), (93.07% + − 6.6%) (4)PBS (60.63% + − 5.8%)
(84.04% + − 4.9%) (4)
Defect (unfilled)
(8.63% + − 1.78%) (4)
2 y 4 weeksMSC-CM group showed higher new bone regeneration compared with control groups, at 4 weeks the defect was completely replaced by mature bone tissue
(Katagiri et al.,2015)% of newly formed bone area in the elevated sinus floorMSC-CM/ B-TCP Aprox. 15%, 22%, 37% (NC)PBS/B-TCP Aprox. 9%,17%, 35% (NC)__2, 4 y 8 weeksSinus floor elevation with MSC-CM/B-TCP enhanced early bone regeneration compared to B-TCP alone
(Katagiri et al.,2016)New formed bone in augmented areaMSC-CM/B-TCP: NRB-TCP: NR__8–9 monthsMSC-CM promoted early bone formation and mineralization compared to B-TCP without MSC-CM, No bone resorption was observed
(Katagiri et al.,2017b)% area of newly formed bone over the total area of the defectMSC-CM (72.3 ± 17.1%) (24)PBS: (30.9 ± 6.2%) (24)Defect (unfilled)(22.2 ± 8.0%) (24)2 weeksMSC-CM enhanced the migration of endogenous cells, which enabled the formation of more blood vessels and bone tissue in the bone defect
(Katagiri et al.,2017a)New formed bone area in maxillary sinus floor elevation.MSC-CM/B-TCP (4) NRB-TCP (2) NR__6 monthsMSC-CM was used safely and enhanced vascularization and early bone formation in maxillary SFE
(Katagiri et al.,2017c)% of the area of newly formed bone over the total area of the defectMSC-CM (74.94 ± 19.11%) (8)PBS: (31.61 ± 5.23%) (8)Defect (unfilled)(15.27 ± 8.21%) (8)2 weeksA higher percentage of bone formation was observed in CM and CC groups, in comparison with the other groups. MSC-CM elicit osteogenesis and angiogenesis
(Kawai et al.,2015)Qualitative description of histological findingsMSC-CM: NRPBS: NRDefect (unfilled) NR2 y 4 weeksMSC-CM promoted periodontal tissue regeneration through mobilization of endogenous MSCs, angiogenesis and differentiation
(Linero & Chaparro,2014)% of regenerated bone tissue, compared to the initial defect.AdMSC-CM: 75% (3)Ad-MSC/HBPH: 62% (4)Blood plasma hydrogel: 32% (4)45 daysAd-MSC improves bone regeneration, and the quantity and quality of regenerated bone is similar with paracrine factors collected and applied as CM instead of Ad-MSCs
(Ogata et al.,2015)Volume of bone sequestra (mm3)MSC-CM Aprox (0.4 mm3) (8)DMEM: Aprox (2.6 mm3) (8)Non treatment: Aprox (2.8 mm3) (8)2 weeksOpen alveolar sockets in 63% of the rats with BRONJ healed with complete soft tissue coverage, whereas the exposed necrotic bone remained in the other groups
(Osugi et al.,2012)% area of newly formed bone over the total area of the defectMSC-CM (49.5% + − 2.7%), (64.4% + − 19.7%)(4)PBS:(24.9% + −  2.2%) (36.1% + −2.9%) (4)Defect (unfilled) (23.4% + − 4.5%) (28.6% + − 5.3%) (4)4 y 8 weeksThe area of ​​new regenerated bone was significantly higher in the MSC-CM group compared to the other groups.
(Qin et al.,2016)Volume of regenerated bone (mm3)Evs-MSC: 4.0 ± 1.9 mm3 (6)Hydrogel 1.3 ± 0.7 mm3 (6)__8 weeksThe Evs derived from human BMSCs contained in gel, accelerated bone regeneration and showed a clear increase in the repair of the defect.
(Sanchooli et al.,2017)New bone volume (mm3)MSC-CM (2.126 + −  0.064) (6), (3.113 + −  0.021 mm3) (6)Collagen gel (1.433 + −  0.266), (2.536 + −  0.085 mm3) (6)Empty defect (0.173 + −  0.060), (0.626 + −  0.104 mm3) (6)4 y 8 weeksSignificantly greater bone volume was observed in the AdMSC-CM group compared with the other groups
(Tsuchiya et al.,2013)% direct implant- bone contact / peri-implant length.MSC-CM (74.3 + − 2.8)(5), (84.7 + −  5.4) (5)PBS: (63.7 + −  5.8) (5) (82.3 + −  2.4) (5)DMEM: (62.3 + −  5) (5), (81.6 + −  4) (5)7 y 28 daysThe removal torque increased gradually over time in the CM group. CM promoted integration into bone during an early stage.
(Tsuchiya et al.,2015)% newly formed bone areaCM 14.5% (3), 24.1% (3)CM-HM 22.7%, 26.9% (3)PBS: 8.1%,
15.8% (3)
4 y 8 weeksBone formation was increased in the CM and CM-HM groups, compared with the other groups.
(Wang et al.,2012b)Bone volume, healing rate of the fracture.MSC-CM (6,6 mm3) 36,8% (19)DM- MEM: (1,7 mm3), 0% (10)Unfilled: (2,5 mm3) 0% (10)8 weeksMSC-CM promoted angiogenesis and fracture healing in a diabetic model. Enhanced bone ingrowth and fracture healing rates compared to the other groups.
(Wang et al.,2015)Ratio of bone volume / total volumeMSC-CM: Aprox 0.04 (4), 0.07 (4)PBS:
0.02 (4), 0.04 (4)
__4 y 8 weeksBone generatioserum was increased in the group of factors secreted by hUCMSCs than in the control group
(Xu et al.,2016)Bone volume / total tissue volumeSecretome: NCPBS: NCSerum-free medium: NC6 weeksThe secretome increased the osteogenic differentiation potential of the rBMSCs and accelerated bone healing and bone consolidation during distraction osteogenesis.
  1. NC Results not clear, approximate values according to graphs; NR It does not report the results. CC Cytokine cocktail. MSC-CM Mesenchymal stem cells- Conditioned medium. FB-CM Fibroblasts conditioned medium. DMEM Dulbecco’s modified Eagle’s medium. DO Distraction osteogenesis. HCM Hypoxic conditioned medium. NCM Normoxic conditioned medium. PBS Phosphate-Buffered Saline, B-TCP Beta–tricalcium phosphate scaffolds. HBPH Human blood plasma hydorgels. Evs Extracellular vesicles. CM-HM Conditioned medium- hydrophilic membrane. hUCMSCs Mesenchymal stem cells derived from human umbilical cord