## 3 Undifferentiated Cells (Stem Cells)
### Adult Stem Cells
#### 3.4.4 Applications in BTE
They subcutaneously implanted the cell-containing constructs in critical-size defects in the immuno-deficient rat calvariant. The results of micro-computed tomography (\(\mu\)-CT), histology, histo-morphometry, and immuno-histochemistry showed that the PDLSC/Bio-Oss\({}^{\circledR}\) construct is superior to the BMMSC/Bio-Oss\({}^{\circledR}\) construct regarding bone healing of critically-sized defects in rats. The potential of ABMSCs to differentiate osteoblasts has been previously investigated under various conditions [323]. However, there are few reports on both in vitro and in vivo osteo-genesis of this type of stem cells. In 2012, [PERSON] et al. evaluated the growth and osteogenic differentiation of ABMSCs on chitosan/hydroxyapatite (CS/HAp) composites [324]. The authors showed that the composites could support the proliferation and attachment of ABMSCs. In addition, the results of ALP staining and gene expression showed that the composites could improve the osteogenic capacity of ABMSCs more than the CS constructs. The in vivo bone regeneration ability of these cells with different carriers has also been evaluated by [PERSON] et al. [325]. In that study, the authors used biphasic HAp/TCP particles or commercial Bio-Oss\({}^{\circledR}\) for cell delivery in a murine ectopic transplantation model. The results showed that both carriers could support the cell attachment. Moreover, a significant newly formed bone tissue was histologically observed in the HAp/TCP groups, while the amounts were lower on the Bio-Oss\({}^{\circledR}\) group. The authors concluded that both types of constructs had a high stem cell-carrying potential. However, the in vivo bone healing process revealed that the osteogenic capacity of hABMSC is affected by the microenvironment on the surfaces of the scaffolds. GMSCs were found to be superior to BM-MSCs for cell therapy in regenerative medicine strategies [326]. [PERSON] et al. summarized the following reasons for their claim: (1) ease isolation, (2) homogeneity and fast proliferation, (3) stable morphology at higher passages, (4) maintaining the normal karyotype and telomerase activity in long-term cultures, and (5) lack of tumorigenicity. Moreover, [PERSON] et al. reported another merit for these cells known as immunomodulatory functions. Specifically, they can suppress peripheral blood lymphocyte proliferation as well as induce the expression of a broad range of immunosuppressive factors (e.g., IL-10, iNOS, and COX-2) in response to the inflammatory cytokine IFN-\(\gamma\)[281]. The osteogenic potential of GMSCs has been previously evaluated and compared to PDLSCs [327]. The obtained results showed that PDLSCs are more effective in terms of osteogenic differentiation as compared to GMSCs. In addition, GMSCs showed fewer inflammation-related changes regarding osteogenic potential in vitro and bone formation in vivo in comparison with PDLSCs. For the functional evaluation of GMSCs for bone regeneration, [PERSON] et al. applied GMSCs with type I collagen in order to fill mandibular and calvarial defects prepared in rats [302]. The histological analyses demonstrated that the cell-containing constructs could repair the mandibular and calvarial defects after two months of surgery. The authors stated that GMSCs could be considered a novel stem cell source with the ability to use bone reconstruction in clinical applications. The capacity of DFPCs regarding inducing calcification had been previously documented in vitro and in vivo [328; 329]. Therefore, it is possible to use this type of cell for bone repair and regeneration strategies. However, there are very few studies regarding the potential of this type of stem cells for BTE strategies.