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

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.

[1]  Baoan Chen,et al.  Mesenchymal stem cells: a promising way in therapies of graft-versus-host disease , 2020, Cancer Cell International.

[2]  А. Г. Демченко,et al.  Экспериментальная ортотопическая имплантация тканеинженерной конструкции трахеи, созданной на основе заселенного мезенхимальными и эпителиальными клетками девитализированного матрикса , 2020 .

[3]  A. Kasaj Gingival recession coverage using soft tissue substitutes , 2019 .

[4]  K. Schlegel,et al.  Gingiva thickening with a porcine collagen matrix in a preclinical dog model. Histological outcomes. , 2019, Journal of clinical periodontology.

[5]  T. Ochiya,et al.  The Immunomodulatory Functions of Mesenchymal Stromal/Stem Cells Mediated via Paracrine Activity , 2019, Journal of clinical medicine.

[6]  C. McCulloch,et al.  Role of Fibroblast Populations in Periodontal Wound Healing and Tissue Remodeling , 2019, Front. Physiol..

[7]  E. Nemoto,et al.  Periodontal Regeneration by Allogeneic Transplantation of Adipose Tissue Derived Multi-Lineage Progenitor Stem Cells in vivo , 2019, Scientific Reports.

[8]  M. McGuire,et al.  Extracellular matrix-based scaffolding technologies for periodontal and peri-implant soft tissue regeneration. , 2019, Journal of periodontology.

[9]  P. Sahrmann,et al.  Early Wound Healing Score: a system to evaluate the early healing of periodontal soft tissue wounds , 2018, Journal of periodontal & implant science.

[10]  M. Martins,et al.  Therapeutic administration of bone marrow‐derived mesenchymal stromal cells reduces airway inflammation without up‐regulating Tregs in experimental asthma , 2018, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[11]  Wen-jian Zhang,et al.  Treatment of gingival defects with gingival mesenchymal stem cells derived from human fetal gingival tissue in a rat model , 2018, Stem cell research & therapeutics.

[12]  M. Casati,et al.  Xenogenous Collagen Matrix and/or Enamel Matrix Derivative for Treatment of Localized Gingival Recessions: A Randomized Clinical Trial. Part I Clinical Outcomes , 2017, Journal of periodontology.

[13]  E. Ponomarev,et al.  Early passage autologous mesenchymal stromal cells accelerate diabetic wound re-epithelialization: A clinical case study. , 2017, Cytotherapy.

[14]  C. C. Villar,et al.  Efficacy of stem cells on periodontal regeneration: Systematic review of pre‐clinical studies , 2017, Journal of periodontal research.

[15]  A. Pabst,et al.  Three-dimensional scanning electron microscopy of maxillofacial biomaterials. , 2017, The British journal of oral & maxillofacial surgery.

[16]  R. Pippi Post-Surgical Clinical Monitoring of Soft Tissue Wound Healing in Periodontal and Implant Surgery , 2017, International journal of medical sciences.

[17]  F. Duan,et al.  Effect of mesenchymal stem cell conditioned medium on human gingival fibroblast proliferation and collagen synthesis , 2017 .

[18]  F. Nociti,et al.  Xenogenous Collagen Matrix and/or Enamel Matrix Derivative for Treatment of Localized Gingival Recessions: A Randomized Clinical Trial. Part II Patient‐Reported Outcomes , 2017, Journal of periodontology.

[19]  S. Gibbs,et al.  Soft Tissue Augmentation Techniques and Materials Used in the Oral Cavity: An Overview , 2016, Implant dentistry.

[20]  D. Agrawal,et al.  Mesenchymal stem cells and cutaneous wound healing: novel methods to increase cell delivery and therapeutic efficacy , 2016, Stem Cell Research & Therapy.

[21]  B. Willershausen,et al.  The influence of various rehydration protocols on biomechanical properties of different acellular tissue matrices , 2015, Clinical Oral Investigations.

[22]  F. Marone,et al.  Synchrotron-based X-ray tomographic microscopy for visualization of three-dimensional collagen matrices , 2015, Clinical Oral Investigations.

[23]  P. Gowda,et al.  Comparative evaluation of efficacy of stem cells in combination with PLA/PGA membrane versus sub-epithelial connective tissue for the treatment of multiple gingival recession defects: a clinical study. , 2014, Journal of stem cells.

[24]  M. Benderitter,et al.  Mesenchymal Stem Cell Therapy Stimulates Endogenous Host Progenitor Cells to Improve Colonic Epithelial Regeneration , 2013, PloS one.

[25]  I. Atsuta,et al.  Stem cells in dentistry--part I: stem cell sources. , 2012, Journal of prosthodontic research.

[26]  H. De Bruyn,et al.  A systematic review on the frequency of advanced recession following single immediate implant treatment. , 2012, Journal of clinical periodontology.

[27]  P. Kasten,et al.  Comparison of immunological properties of bone marrow stromal cells and adipose tissue-derived stem cells before and after osteogenic differentiation in vitro. , 2007, Tissue engineering.

[28]  I. V. Potapov,et al.  First experience in the use of bone marrow mesenchymal stem cells for the treatment of a patient with deep skin burns , 2005, Bulletin of Experimental Biology and Medicine.

[29]  W. Young,et al.  Tissue engineering for bone regeneration using differentiated alveolar bone cells in collagen scaffolds. , 2003, Tissue engineering.

[30]  Tatsuo Nakamura,et al.  Novel approach to regeneration of periodontal tissues based on in situ tissue engineering: effects of controlled release of basic fibroblast growth factor from a sandwich membrane. , 2003, Tissue engineering.