14. The Effect of Stem Cells on Acute Wound Healing

• Published in: Journal of Nippon Medical School Vol. 75; no. 2; p. 133
• Main Authors: Ahmet Cagri Uysal, Hiroshi Mizuno, Morikuni Tobita, Hiko Hyakusoku
• Format: Journal Article
• Language: Japanese
• Published: The Medical Association of Nippon Medical School 2008
• ISSN: 1345-4676; 1347-3409

Introduction: Mesenchymal stem cells control critical points in healing processes with direct and indirect effects. The direct effect-i.e. the differentiation potential-of mesenchymal stem cells makes them applicable in various different situations. Mesenchymal stem cells have been proven to improve angiogenesis in any situation where neovascularization is necessary. We have performed an experimental study to determine the effect of mesenchymal stem cells (bone marrowderived stem cells [BSCs] and adipose-derived stem cells [ASCs]) on acute wound healing in a rat model. Materials and Methods: Eight Wistar rats were employed in the study. The ASCs were gathered from their inguinal fat pads, and the BSCs from the femur and tibia. After three passages in a control medium (Dulbeco's Modified Eagle's Medium [DMEM], 10% fetal bovine serum [FBS]), the cells were prepared for injection so that each injection included 1 × 107 cells. The cells were labeled with DiI staining before injection for tracing. Four circular skin defects with a diameter of 2 cm were made on the dorsum of each rat up to the muscle fascia, and the rats were separated into four groups according to treatment: Group 1: control group PBS; Group 2: ASCs; Group 3: BSCs; Group 4: full thickness skin graft. Healing was monitored daily, and the day of total epithelization was recorded for each group. On the day when healing was complete, photographs were taken to evaluate the total area of scar formation. Samples were then examined for histology and immunohistochemistry. Results: The healing times were recorded for each group: Group 1: 52.50 ± 4.29 days; Group 2: 47.13 ± 3.37 days; Group 3: 47.50 ± 4.34 days; Group 4: 44.25 ± 4.77 days. There was a statistically significant difference between the control group and groups 2, 3 and 4 when compared individually (p＜0.05). Macroscopical photographs were evaluated with Adobe Photoshop and the number of pixels of the total area of scar formation was noted: Group 1: 247,689.88 ± 23,203.56 pixels; Group 2: 311,752.63 ± 18,640.06; Group 3: 322,069.13 ± 22,043.52; Group 4: 392,873.13 ± 30,719.40. The total scar area was highest in group 4 and smallest in group 1. There was a statistically significant difference between the control group and groups 2, 3 and 4 when compared individually (p＜0.05). The vascular density of histological specimens in 20 fields under ×20 magnification (Group 1: 2.37 ± 0.12; Group 2: 6.71 ± 0.74; Group 3: 5.94 ± 0.78; Group 4: 2.45 ± 0.18) was statistically greater in groups 2 and 3 when compared individually with groups 1 and 4 (p＜0.5). Anti-VWF Ab staining revealed differentiation of stem cells into new endothelial cells. Anticytokeratin Ab immunohistochemical staining indicated that some of the epithelial cells had originated from the injected stem cells. Conclusion: ASCs and BSCs do not only decrease healing time and help in faster primary healing but can also differentiate into the required cells and tissues in the absence of any scaffold. Although they improve healing time, however, ASCs and BSCs do not decrease scar formation in the skin. This might be due to their inhibition of the myofibroblasts that would lead to a better quality of healing. Investigation of this issue continues in our laboratory.