Mesenchymal Stromal Cells Enhance Vascularization and Epithelialization within 7 Days after Gingival Augmentation with Collagen Matrices in Rabbits

Abstract

Soft gingival tissue deficiency remains a severe problem leading to postoperative recession, peri-implantitis, and bone resorption. The use of collagen matrices does not always lead to complete rebuilding of the gingiva volume. The application of mesenchymal stromal cells (MSCs) simultaneously with collagen materials represents a promising approach for the restoration of soft gingival tissues. However, short-term effects of MSCs-enriched collagen grafts after gingival augmentation have not yet been studied properly. Mucograft and Mucoderm matrices were implanted in rabbits (n = 12) simultaneously with the intraoperative injection of rabbit bone marrow-derived mesenchymal stromal cells (BM-MSCs) or without cells. Collagen matrices were implanted under the flap or by the surface technique without intentional primary closure. The samples were harvested seven days after implantation, histological staining with hematoxylin and eosin, and immunohistochemical staining for VEGF, IGF1, and TGF were performed. The use of Mucoderm led to better augmentation outcomes on day 7 compared with Mucograft (p < 0.0001). Gingival augmentation in combination with the local administration of BM-MSCs led to better regeneration of the soft gingival tissues independently of the type of implanted collagen matrices (p < 0.0001). Furthermore, injection of BM-MSCs significantly enhanced gingival vascularization and epithelization with a clear positive correlation between vascular growth and epithelial response. Administration of BM-MSCs in combination with various collagen materials may potentially improve gingiva regeneration.

Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

“…MSCs secrete multiple growth factors and cytokines that also determine their regenerative effect. In particular, being derived from human umbilical cord, MSCs release keratinocyte growth factor (KGF) ( 18 ), hepatocyte growth factor (HGF) ( 19 ), transforming growth factor-β (TGF-β) ( 20 ) and exosomes, which suppress inflammation and lead to improved vascularization and epithelialization in affected tissues ( 21 ).…”

Adipose-Derived Stromal Cells within a Gelatin Matrix Acquire Enhanced Regenerative and Angiogenic Properties: A Pre-Clinical Study for Application to Chronic Wounds

“…In line with this data, gelatin was shown to directly enhance wound closure [ 39 ], particularly by increasing angiogenesis, keratinocyte and fibroblast proliferation/migration and myofibroblast differentiation [ 42 , 43 , 44 ]. Interestingly, the local administration mesenchymal stem cells in a collagen scaffold led to better regeneration of soft gingival tissues in rabbits through enhanced gingival vascularization and epithelization with a clear positive correlation between vascular growth and epithelial response [ 45 ]. Additionally, epithelialization and angiogenesis were linked in another study where diabetic wounds received mesenchymal stem cells activated with LPS: the granulation tissue of treated wounds had higher pronounced epithelialization and associated vascularization compared with controls [ 46 ].…”

Mesenchymal Stromal Cells as a Driver of Inflammaging

“…Adult stem cells including MSCs are the most commonly used cell type for regenerative medicine and tissue engineering since the first clinical trial in 1995 [ 6 , 7 ]. Since the mid1990s a considerable amount of literature postulated cellular differentiation as a key-issue of their action, while recent studies emphasize the role of immunomodulatory cross-talks derived by MSCs secretome [ 8 ].…”