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Table 1. Summary of available evidence for periodontal regeneration with mesenchymal stem cells
Bone regeneration PL Cementum
BMMSC Effective in grade III furcation defects, Effective in grade III furcation defects; Effective in grade III furcation defects
but bone fill is not complete; Conflicting results; effective only
Ineffective when used without bone associated with bone substitutes
substitutes
ASC Effective in extraction sockets Effective in surgically created intrabony Effective in surgically created intrabony
defects defects
PDLSC Effective in fenestration; No added Effective in fenestration; More effective Effective in fenestration; added
benefit associated with non reservable than BMMSC; benefit associated with non reservable
membranes in fenestrations; Effective Effective in intrabony defects with better membranes in fenestrations: Effective
in intrabony defects only using bone results using bone substitutes in intrabony defects with better results
substitutes using bone substitutes
DPSC Effective in extraction sockets; Improve Improve regeneration in intrabony Improve regeneration in intrabony
bone regeneration in intrabony defects defects defects
DFPC Improve effects of PDLSC Improve effects of PDLSC Improve effects of PDLSC
SHED Increased bone volume in intrabony Increased PL fibers in intrabony defects Increased in intrabony defects
defects
SCAP Increased bone volume in intrabony Increased in intrabony defects compared Increased in intrabony defects compared
defects compared to saline to saline to saline
BMMSC: bone marrow mesenchymal stem cell; ASC: adipose-derived stem cell; PDLSC: periodontal ligament stem cell; DPSC: dental
pulp stem cell; DFPC: dental follicle precursor cell; SHED: stem cell from human exfoliated teeth; SCAP: stem cell from apical papilla

[65]
[66]
methods ; the way of delivery and implantation in combination with membranes ; and biomaterials [67,68]
or bioactive molecules [69,70] .
Briefly, age has no effect on the possibility of isolating and culturing stem cells, but showed a statistically
significant effect on the procedure outcome. Cells harvested from donors over 60 years of age had an over
50% failure rate. On the contrary, in younger donors (≤ 60 years old), the failure rate ranged between 14%
[64]
and 22%. No effect of gender was found, with similar success rates for male and female donors .
It has been suggested that the site of harvesting can also influence the outcomes of the cell therapy
procedures, according to the differences found in stem cells of the same lineage but taken from different
[64]
niches. More studies are needed to confirm this finding .

The culture and the expansion protocols used to amplify the numbers of transplanted cells are a variable
that can alter the “stemness” properties of the stem cells. No clear protocol has been developed yet for the
treatment of MSCs, in particular oral ones. We know that under certain conditions (i.e., particular culture
mediums) we can alter the differentiation path, favoring a subset of cells that can increase the successful
[71]
outcomes of our cell treatments ; however, further research is needed to better understand and guide this
process.

Finally, the protocols wherewith these cells are administered can have a positive or negative effect on the
final result. Cell therapy can be administered on a scaffold base or on a scaffold-free delivery system. The
first one implies the use of a biomaterial, usually calcium-based, a membrane, or a combination of the
two. The rational behind the use of biomaterials and membranes is the need for blood clot stability in
order to reach its formation and maturation. When the conformation of the periodontal defect is not firm
enough, biomaterials and membranes can make up for the lack of stability and enhance the regeneration
process. It has been shown, also in vivo, that different materials have different effects, either positive or
[30]
negative, on the non-cell-based regeneration techniques . Similarly, these effects have been found in cell-
based regenerative therapies, with promising results from beta-TCP [46,72-74] , hyaluronic acid [75,76] , and nano
designed materials [77-79] .