Autologous adipose-derived stem cell transplantation enhances healing of wound with exposed bone in a rat model

Abstract

18Objectives. Soft tissue wounds with exposed bone often require extended healing times 19 and can be associated with severe complications. We describe the ability of artificial 20 dermis with autogenic adipose-derived stem cells (ADSCs) to promote the healing of 21 wounds with exposed bone in a rat model. 22Methods. Adipose tissues harvested from the bilateral inguinal regions of Wistar rats 23 were used as ADSCs. Rats were randomly divided into control and ADSC groups to 24 investigate the efficacy of ADSC transplantation for wound healing (n=20 per group). 25Soft tissue defects were created on the heads of the rats and were covered with artificial 26 dermis with or without the seeded ADSCs. Specimens from these rats were evaluated 27 using digital image analysis, histology, immunohistochemistry, cell labeling, and real-28 time reverse-transcription polymerase chain reaction (Real-time RT-PCR). 29Results. The average global wound area was significantly smaller in the ADSC group 30 than in the control group on days 3, 7, and 14 after surgery (p<0.05). After 14 days, the 31 blood vessel density in the wound increased by 1.6-fold in the ADSC group compared 32 with that in the control group (p<0.01). Real-time RT-PCR results showed higher Fgfb 33 and Vegf expression levels at all time points, and higher Tgfb1 and Tgfb3 expression 34 levels until 14 days after surgery, in the ADSC group than in the control group 35 (p<0.05). 36Conclusions. In wounds with exposed bone, autogenic ADSCs can promote 37 vascularization and wound healing. Use of this cell source has multiple benefits, 38 including convenient clinical application and lack of ethical concerns. 39 3 40 41 Introduction 42Some wounds caused by ulcers, trauma, and various operations, result in exposed bone, 43 leading to severe complications in many cases during treatment of soft tissue. Currently, 44 surgical treatment for defects with exposed bone typically involves the use of local or 45 distal skin flaps, muscle flaps, or myocutaneous flaps. However, there are many risks 46 associated with wound coverage by these flaps, and a complicated microsurgical 47 approach is required for successful treatment. Moreover, use of a composite tissue 48 transfer technique may not be possible in such cases owing to the paucity of the graft 49 donor site and other factors.50Artificial dermis is a commercially available treatment for full-thickness skin defects 51 after debridement. It has been successfully used to promote healing by creating a 52 vascular matrix over an exposed bone in clinical reports [1,2]. However, the formation 53 of neodermal tissue is delayed, thus prolonging the treatment period. A main reason for 54 prolonging the treatment period is the slow vascularization rate [3]. Several recent 55 studies have shown that in the context of tissue injury, mesenchymal stem cells (MSCs) 56 exhibit excellent potential for promoting healing and vascularization of wounds [4,5]. 57Among the various types of MSCs, adipose-derived stromal stem cells (ADSCs) have 58...

Combinational therapy with antibiotics and antibiotic-loaded adipose-derived stem cells reduce abscess formation in implant-related infection in rats

“…One limitation of using ADSCs as a delivery vehicle for antibiotics is that their ability to do so is dependent on cell viability and integration at the injection site. By using DiI staining of ADSCs, a previous study showed that numerous ADSCs were distributed throughout granulation tissue up to 21 days post-transplantation 13 . We did not study cell viability and distribution after injection, which requires further study.…”

“…ADSC and BMSCs for in vitro experiments were isolated from 20 9-week-old female Wistar rats (Japan SLC Co., Shizuoka, Japan). ADSCs were prepared as previously reported 13 , with modification. BMSCs were isolated from the same rats, as previously reported 51 , with modifications in the protocol.…”

“…Among the various types of MSCs, ADSCs have numerous unique advantages. They are abundant in subcutaneous adipose tissues and can be easily harvested using a syringe or by minimally invasive lipoaspiration 13 . In addition, they contribute to the complex wound-repair processes, comprising inflammation, granulation, and remodelling 14,15 .…”

Free adipose tissue (FAT) graft pooling for severe dead space management

“…Hamada et al (3) , comparing artificial dermis with adipose-derived stem cells in wounds with exposed bone in a rat model, reported that adipose-derived stem cells showed significantly higher expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), thereby exhibiting potential for differentiation into fibroblasts and blood vessel endothelial cells.…”

“…The successful use of adipose-derived stromal/stem cells has been reported in aesthetic, cardiac, and reconstructive posttraumatic procedures (2) . Potential advantages of autologous fat grafting include abundant fat, easy harvesting via liposuction, and cost-effectiveness compared to commercially available artificial skin (3) .…”