Table 2 Results of studies

(Ando et al.,2014)

% of new bone callus in the distraction gap

MSC-CM 62% (10)

FB-CM: 37%(10)

DMEM: 32% (10)

15 days

MSC-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 defect

HCM:NC

NCM: NC

__

56 days

Bone 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 cortices

MSC-CM (9): NC

Exosomes (9): NC

PBS (15): NC

6 weeks

MSC-derived exosomes rescued the retardation of fracture healing in CD9 −/− mice

(Inukai et al.,2013)

Bone regeneration area

MSC-CM /Scaffold: 4.89 ± 1.08 mm2 (6)

PBS/ Scaffold: 2,4 mm2 (6)

No implant/Scaffold: 1,8 mm2 (6)

4 weeks

Large 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 defect

MSC-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 weeks

MSC-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 floor

MSC-CM/ B-TCP Aprox. 15%, 22%, 37% (NC)

PBS/B-TCP Aprox. 9%,17%, 35% (NC)

__

2, 4 y 8 weeks

Sinus 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 area

MSC-CM/B-TCP: NR

B-TCP: NR

__

8–9 months

MSC-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 defect

MSC-CM (72.3 ± 17.1%) (24)

PBS: (30.9 ± 6.2%) (24)

Defect (unfilled)(22.2 ± 8.0%) (24)

2 weeks

MSC-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) NR

B-TCP (2) NR

__

6 months

MSC-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 defect

MSC-CM (74.94 ± 19.11%) (8)

PBS: (31.61 ± 5.23%) (8)

Defect (unfilled)(15.27 ± 8.21%) (8)

2 weeks

A 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 findings

MSC-CM: NR

PBS: NR

Defect (unfilled) NR

2 y 4 weeks

MSC-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 days

Ad-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 weeks

Open 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 defect

MSC-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 weeks

The 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 weeks

The 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 weeks

Significantly 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 days

The 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 area

CM 14.5% (3), 24.1% (3)

CM-HM 22.7%, 26.9% (3)

PBS: 8.1%,

15.8% (3)

4 y 8 weeks

Bone 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 weeks

MSC-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 volume

MSC-CM: Aprox 0.04 (4), 0.07 (4)

PBS:

0.02 (4), 0.04 (4)

__

4 y 8 weeks

Bone generatioserum was increased in the group of factors secreted by hUCMSCs than in the control group

(Xu et al.,2016)

Bone volume / total tissue volume

Secretome: NC

PBS: NC

Serum-free medium: NC

6 weeks

The secretome increased the osteogenic differentiation potential of the rBMSCs and accelerated bone healing and bone consolidation during distraction osteogenesis.