Promotion of skin wound healing using prevascularized oral mucosal cell sheet

Abstract

Background This study examined the potential use of our newly developed prevascularized oral mucosal cell sheet for the treatment of skin wounds. Methods Mucosal cell sheets containing cultured keratinocytes and plasma fibrin without (K sheet) or with a mixture of fibroblasts and endothelial progenitor cells (PV sheet) were transplanted into full‐thickness skin excisional wounds of nude mice. Results This technique was successful for in vitro culture; expanding keratinocytes, fibroblasts, and endothelial progenitor cells; and generating prevascularized mucosal cell sheets. Cell sheets promoted in vivo wound healing with rapid wound closure and less scarring compared to controls. This result was more apparent in the PV than the K sheet (P < .05). Wounds covered with cell sheets showed less expression of TGFB1, ACTA2, and FN1 mRNAs than the controls (P < .05). Conclusion The prevascularized mucosal cell sheet showed in vivo efficacy and tissue plasticity in cutaneous wounds by promoting accelerated healing.

Engineered Prevascularization for Oral Tissue Grafting: A Systematic Review

“…The flow chart of screening and selection processes is presented in Figure 1. Twelve studies originated from Asia, [9][10][11][12][13][14][15][16][17][18][19][20] eight from North America (all from the United States), [21][22][23][24][25][26][27] and four from Europe. [28][29][30][31] Details concerning experimental groups and animal intervention are presented in Table 1.…”

“…16,26,28,31 One study cited European legislation, the Directive 2010/63/EU about the protection of animals used for scientific purposes. 28 Two studies used the Animal Research Reporting In Vivo Experiments (ARRIVE) Guidelines 18,19 that were first published in 2010 to improve animal studies reporting. 32 Factors needed to obtain the prevascularized grafts (Table 3) Sources of cells.…”

“…The oral cavity contains various types of tissues with specific functions, and this variability was found in the review. Ten studies focused on bone as its reconstruction is a critical issue in tissue engineering, 16,18,[24][25][26][27][28][29]31 while eight studies dealt with soft tissues, particularly oral mucosa, 14,17,19,30 dental pulp 9,12 two studies, periodontium, 15 and skin 20 (Table 3). Six studies used autologous animal cells.…”

“…33 Therefore, stem cells became a new target, especially with recent studies showing that the oral cavity provides multiple sources of stem cells such as oral soft tissues, the periodontal ligament, or the dental pulp. 34 As in literature, selected studies reported the following target cells used: (i) Mesenchymal stem cells (MSC) mainly from bone marrow or adipose tissue 10,11,16,18,20,24,[27][28][29]35 (ii) Oral stem cells: Periodontal ligament stem cells, 13,15 dental pulp stem cells, 9 and stem cells from human exfoliated deciduous teeth 12 (iii) Oral stromal cells: fibroblasts and keratinocytes 14,17,19,30 (iv) Induced pluripotent stem cells 16,26 (v) Other cells: normal human lung fibroblasts, 21 osteoblast-like cells, 31 pericytes 26 Endothelial cells being a crucial element to provide vascularization, their provenance was evaluated as well. Human umbilical vein endothelial cells (HUVEC) were used in 13 studies ( Table 3).…”

“…Human umbilical vein endothelial cells (HUVEC) were used in 13 studies ( Table 3). Other endothelial cell types used to a lesser extent were endothelial progenitor cells, 14,17,19,29 human dermal microvascular endothelial cells, 30 cells from aortic fragments, 31 amniotic fluid-derived stem cellsendothelial cells, 22 and stromal vascular fraction derived cells 25 (Table 3).…”