Effect of Inflammation on Gingival Mesenchymal Stem/Progenitor Cells’ Proliferation and Migration through Microperforated Membranes: An In Vitro Study

Abstract

Background. In the field of periodontal guided tissue regeneration, microperforated membranes have recently proved to be very promising periodontal regenerative tissue engineering tools. Regenerative periodontal approaches, employing gingival mesenchymal stem/progenitor cells in combination with these novel membranes, would occur mostly in inflamed microenvironmental conditions intraorally. This in turn entails the investigation into how inflammation would affect the proliferation as well as the migration dynamics of gingival mesenchymal stem/progenitor cells. Materials and Methods. Clones of human gingival mesenchymal stem/progenitor cells (GMSCs) from inflamed gingival tissues were characterized for stem/progenitor cells’ characteristics and compared to clones of healthy human GMSCs (n=3), to be subsequently seeded on perforated collagen-coated poly-tetra-floro-ethylene (PTFE) membranes with a pore size 0.4 and 3 microns and polycarbonic acid membranes of 8 microns pore size in Transwell systems. The population doubling time and the MTT test of both populations were determined. Fetal bovine serum (FBS) was used as a chemoattractant in the culturing systems, and both groups were compared to their negative controls without FBS. Following 24 hours of incubation period, migrating cells were determined on the undersurface of microperforated membranes and the membrane-seeded cells were examined by scanning electron microscopy. Results. GMSCs demonstrated all predefined stem/progenitor cell characteristics. GMSCs from inflamed gingival tissues showed significantly shorter population doubling times. GMSCs of inflamed and healthy tissues did not show significant differences in their migration abilities towards the chemoattractant, with no cellular migration observed in the absence of FBS. GMSCs from healthy gingival tissue migrated significantly better through larger micropores (8 microns). Scanning electron microscopic images proved the migratory activity of the cells through the membrane pores. Conclusions. Inflammation appears to boost the proliferative abilities of GMSCs. In terms of migration through membrane pores, GMSCs from healthy as well as inflamed gingival tissues do not demonstrate a difference in their migration abilities through smaller pore sizes, whereas GMSCs from healthy gingival tissues appear to migrate significantly better through larger micropores.

Ascorbic Acid, Inflammatory Cytokines (IL-1β/TNF-α/IFN-γ), or Their Combination’s Effect on Stemness, Proliferation, and Differentiation of Gingival Mesenchymal Stem/Progenitor Cells

“…Similar to previous investigations [ 21 , 37 – 40 ], the tested G-MSCs showed all predefined stem/progenitor cells' hallmarks encompassing CFUs ability, surface markers' expression, and a remarkable multilineage differentiation capacity [ 41 ]. Recently, multiple investigations have revealed that local microenvironmental inflammatory stimuli could uplift G-MSCs' reparative and regenerative potentials [ 16 – 19 , 42 , 43 ]. The currently investigated G-MSCs were stimulated via periodontal proinflammatory cytokines, namely IL-1 β , TNF- α , and IFN- γ [ 16 ], by AA or their combination.…”

The Therapeutic Potential of Inflamed Gingiva-Derived Mesenchymal Stem Cells in Preclinical Studies: A Scoping Review of a Unique Biomedical Waste

“…The majority of studies provided information about the diseased tissue sampling, while one article did not report the details [ 12 ]. MSCs from diseased gingiva were collected, whether directly during the gingivectomy procedure, extraction of periodontally affected teeth, and flap debridement [ 6 – 8 , 13 , 31 , 32 , 35 ] or indirectly via inflammatory preconditioned culture.…”

“…Concerning the migration dynamics, GMSCs whether from healthy or inflamed tissues exhibited a similar migration pattern toward chemoattractant through smaller pore sizes. It is worth noting that a better migratory activity was reported in GMSCs derived from healthy tissues in the case of large pore-sized membrane [ 12 ].…”

Therapeutic Functions of Stem Cells from Oral Cavity: An Update

“…In the immunophenotypic analysis, GMSCs are positive for classical MSC markers including CD29, CD44, CD73, CD90, and CD105 while negative for hematopoietic lineage cell markers such as CD14, CD34, and CD45 [45,46]. They can self-renew while maintaining the long-term proliferative capacity with a faster population doubling time compared to BM-MSCs [47,48].…”