Subcutaneously administrated cells or drugs are reported to take a few days to be delivered into the body through vessel bloods [33, 34]. This may be owed to difficulty of the cells in securing vascular accesses to the target site because of a lack of blood vessels at the buccinators, while systemic MSC homing occurs more readily through the bloodstream [35].

The effects of MSC treatment on levels of serum inflammatory cytokines IL-2, IL-4, and IL-10 in the implant model rat are shown (Fig. 4d). Systemic MSC injection resulted in lower IL-2 and IL-4 levels and higher IL-10 levels compared with local MSC injection and the control.

An interesting study disclosed that intraperitoneal MSCs migrated and engrafted at the inflamed colon and passed through the whole intestinal wall reaching the luminal side [36]. Although we were unable to trace the exact migration of our locally administrated MSCs by observed fragmentary, in vivo imaging or tracking with superparamagnetic iron oxide might enable this using a series of flow [14, 37].

In this study, GFP-MSCs took several days to be observed at the target organ after local injection (Fig. 5B (b, c)). Some cells were observed in the mass of the injected area (Fig. 5B(a)), while others were observed indirectly circulating within the whole body or were slightly accumulating at the wound area (Fig. 5B (d)). Specially, these results showed that the most of injected MSCs in the local group got delayed to accumulate around the implant. In the systemic group, GFP/CD-90 double-positive cells were observed around the apical portion of the PIE-like epithelial structure at days 3 and 5 (Fig. 5B (b, c)), after which positive staining declined over time. In the local group, MSC location was limited to the buccal mucosa near the experimental implant at early stage; however, MSC accumulation was observed at the mucosa around the implant from day 5 onwards (Fig 5B). On the contrary, the MSCs did not accumulate on the implant surface, unlike in the systemic group, and they remained around the implantation site for approximately 1 week.