Table 1.

Preclinical studies selected according to eligibility criteria.

Reference	Stem Cells Source	Treatment Groups Delivery System	Intervention Implantation Site	Analysis	Main Outcomes Conclusions
Cassaro et al., 2019 [31]	Allogeneic rats BM-MSCs (femurs/tibias)	G1: No filling G2: Biphasic calcium phosphate (BCP) G3: Fibrin biopolymer (FBP) + BCP G4: FBP + MSCs G5: FBP + BCP + MSCs	Implantation of the scaffold in a 5 mm bone defect in the right femur of the rats (n = 8). Analyzes were performed after 30 and 60 days of the procedures.	Computed tomography, scanning electron microscopy and histological analysis.	All groups exhibited bone matrix formation, with significantly higher bone formation in FBP + MSCs. FBP proved to be an excellent scaffold for bone repair therapies.
Chen et al., 2014 [32]	Allogeneic rabbits BM-MSCs (femurs)	G1: Decalcified bone matrix (DBM) + fibrin gel (FG) + MSCs G2: DBM + FG G3: No filling	Implantation of the scaffold in a 10 mm bone defect in the left femur of the rabbits (n = 10). Analyzes were performed after 12 weeks of the procedures.	Serum proteomics (2D-PAGE and MALDI-TOF-TOF-MS), hematoxylin–eosin (HE) staining, ALP staining and osteopontin immunofluorescence detection.	DBM + FG + MSCs exhibited better bone regeneration than other groups. The combination of DBM + FG + MSCs can result in successful bone formation and can be used as a scaffold for bone tissue engineering.
Han et al., 2014 [33]	Human AD-MSCs (human abdominal fat)	G1: Decalcified bone matrix (DBM) + fibrin glue (FG) G2: MSCs + FG G3: MSCs + DBM + FG G4: No filling	Implantation of the scaffold in a 10 mm cranial defects in rabbits (n = 5). Analyzes were performed after 6 weeks of the procedures.	Computed tomography and histological analysis.	MSCs + DBM + FG presented better bone formation than others groups. Scaffold containing MSCs could be helpful in the correction of extensive bone defects.
Hao et al., 2014 [34]	Allogeneic rats BM-MSCs (femurs/tibias)	G1: control group G2: atrophic nonunion Group—fibrin glue (FG) G3: experimental group (MSCs + FG)	Injection of FG and MSCs + FG into the osteotomized right rat femur (with a length of 1 mm) of G2 and G3, respectively (n = 12). Analyzes were performed after 8 weeks of the procedures.	Radiographic and histological analysis. Biomechanical test.	MSCs + FG presented complete bony bridging of the osteotomy gap, with the formation of plenty of woven bone. Local injection of MSCs seeded fibrin glue promoted atrophic nonunion repair.
Kang et al., 2010, [35]	Autogenous pigs skin-derived MSCs (SD-MSCs) (ears)	G1: Demineralized bone (DMB) + fibrin glue (FG) + MSCs G2: Demineralized bone (DMB) + fibrin glue (FG)	Implantation of the scaffold in a lateral window (1 cm) in maxillary sinus of 4 pigs. In each pig, one maxillary sinus received only the scaffold and the other sinus received the scaffold with MSCs. Analyzes were performed after 2 and 4 weeks of the procedures.	Histological analysis.	Trabecular bone formation were more pronounced in DMB + FG + MSCs, Autogenous MSCs grafting with a DMB + FG scaffold can serve as a predictable alternative to bone grafting in the maxillary sinus floor.
Khanmoha-mmadi et al., 2019 [36]	Human menstrual blood-derived stem cells (MenSCs)	G1: Right defect: fibrin glue (FG) + MenSCs Left defect: FG G2: Left defect: No filling	Implantation of the scaffold in a knees osteochondral defects (3 × 4 mm2) of the rabbits (n = 12). Analyzes were performed after 3 and 6 months of the procedures.	Gross morphological and histological analysis.	The most regenerated tissue in FG + MenSCs was similar to hyaline cartilage and it was higher than other experimental groups. MenSCs encapsulated in FG was more effective in defect repair compared to FG alone.
Kim et al., 2012 [37]	Autogenous Rats AD-MSCs (inguinal adipose tissue)	G1: Fibrin glue (FG) G2: FG + Demineralized Bone Matrix (DBX) G3: FG + DBX + MSCs G4: FG + DBX + iMSCs (osteogenic induced)	Implantation of the scaffold in a 8 mm critical calvarial bone defect in rats (n = 10). Analyzes were performed after 8 weeks of the procedures.	Radiographic, histological and radiodensitometric analysis.	The mean radiodensity of the FG, FG + DBX, FG + DBX + MSCs and FG + DBX + iMSCs groups was 16.78%, 39.94%, 25.58% and 51.31%, respectively. FG + DBX + iMSCs group showed the better potential to regenerate bone defects.
Lazarini et al., 2017 [38]	Human AD-MSCs (abdominal liposuction)	Type II collagen hydrogel and fibrin sealant implant with (right knee) or without AD-MSCs (left knee)	Implantation of the scaffold in a 3 mm knees defects in 4 rabbits. Analyzes were performed after 12 weeks of the procedures.	Histological analysis.	Scaffold containing MSCs induced greater repair of chondral lesions and better cell organization and alignment of collagen fibers compared to the isolated use of the scaffold, being effective for articular cartilage repair.
Lee et al., 2008 [39]	Autogenous Rabbits BM-MSCs (iliac bone)	Group 1 (15 rabbits): Defect 1: MSCs + autologous fibrin glue (AFG) Defect 2: MSCs + macroporous biphasic calcium phosphate (MBCP) Defect 3: No filling Group 2 (3 rabbits): Defect 1: AFG Defect 2: MBCP Defect 3: No filling	Implantation of the scaffold in a 6 mm cranial defects (3 defects/rabbit). Analyzes were performed after 1, 2 and 3 months of the procedures.	Radiographic and histological analysis.	MSCs + AFG induced more bone formation 2 months post operation and more mature bone was found 3 months post operation compared with the other groups. MSCs + AFG resulted in earlier and more mature new bone formation.
Mehrabani et al., 2018 [40]	Allogeneic Rabbits AD-MSCs (subcutaneous adipose tissue)	G1: (n = 10) Right defect: autologous fibrin glue + MSCs Left defect: No filling (control) G2: (n = 10) Right defect: autologous fibrin glue Left defect: autologous bone graft (iliac crest)	Implantation of the scaffold in a bilateral 1.5 × 0.5 cm uni-cortical mandibular osteotomies in 20 rabbits. Analyzes were performed after 28 and 56 days of the procedures.	Computed tomography and histopathological analysis	There was accelerated osteogenesis in the treated defects, with better bone formation in FG + MSCs and autologous bone graft groups, which showed a significant and similar increase in the thickness of new cortical bone. FG + MSCs presented a remarkable reconstruction of cortical bone.
Zhang et al., 2012 [41]	Allogeneic rats BM-MSCs (femurs)	G1: blank (no filling) G2: fibrin glue (FG) G3: FG + MSCs	Implantation of the scaffold in a bilateral maxillar defects (3 mm) in rats (n = 5). Analyzes were performed after 6 weeks of the procedures.	Histological analysis and micro-CT.	The amount of new bone formed in the FG + MSCs was significantly greater than the others groups. The strategy of combing MSCs with FG is effective in the repair of alveolar bone defects.
Orsi et al., 2017 [42]	Allogeneic rats BM-MSCs (femurs)	Non-ovariectomized (NOVX): G1: Fibrin sealant (FS) G2: FS + MSCs G3: FS + iMSCs (differentiated in osteogenic lineage) G4: No filling G5: No injury Ovariectomized (OVX): G1: FS G2: FS + MSCs G3: FS + iMSCs G4: No filling G5: No injury	Implantation of the scaffold in a femur defects (5 mm) in rats (n = 4). Analyzes were performed after 14 and 28 days of the procedures.	Microcomputed tomography, biochemical analysis, radiographic and histology analysis, scanning electron microscopy.	After 14 days, in both the OVX and NOVX animals, FS + MSCs and FS + iMSCs showed a higher formation of bone cells in relation to the control group. Bone neoformation was observed in all treated and control groups. No morphological differences in the femurs of the NOVX and OVX animals were observed after the surgery.