Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats

Abstract

PurposeThis experimental study verified the effect of adipose-tissue-derived stem cells (ASCs) on the healing of ischemic colonic anastomoses in rats.MethodsASCs were isolated from the subcutaneous fat tissue of rats and identified as mesenchymal stem cells by identification of different potentials. An animal model of colonic ischemic anastomosis was induced by modifying Nagahata's method. Sixty male Sprague-Dawley rats (10-week-old, 370 ± 50 g) were divided into two groups (n = 30 each): a control group in which the anastomosis was sutured in a single layer with 6-0 polypropylene without any treatment and an ASCtreated group (ASC group) in which the anastomosis was sutured as in the control group, but then ASCs were locally transplanted into the bowel wall around the anastomosis. The rats were sacrificed on postoperative day 7. Healing of the anastomoses was assessed by measuring loss of body weight, wound infection, anastomotic leakage, mortality, adhesion formation, ileus, anastomotic stricture, anastomotic bursting pressure, histopathological features, and microvascular density.ResultsNo differences in wound infection, anastomotic leakage, or mortality between the two groups were observed. The ASC group had significantly more favorable anastomotic healing, including less body weight lost, less ileus, and fewer ulcers and strictures, than the control group. ASCs augmented bursting pressure and collagen deposition. The histopathological features were significantly more favorable in the ASC group, and microvascular density was significantly higher than it was in the control group.ConclusionLocally-transplanted ASCs enhanced healing of ischemic colonic anastomoses by increasing angiogenesis. ASCs could be a novel strategy for accelerating healing of colonic ischemic risk anastomoses.

Autologous adipose-derived stem cell sheets enhance the strength of intestinal anastomosis

“…Although several experimental studies have reported that local injection of cell suspensions of ASCs into intestinal anastomotic sites has a beneficial effect on the healing process at the anastomotic sites under normal wound-healing conditions [21] , [22] , it is difficult to compare these results with those of the present study as the experimental animals, injury models, and suturing pitches are different. Okano et al.…”

“…The cell sheets can maintain their functional capability and structure after transplantation, and with the presence of deposited extracellular matrix on the basal surface, the cell sheets can therefore be transplanted without the need for sutures or clips [36] , [37] . As we used large animals and created delayed wound-healing conditions, we consider that our study results are more relevant clinically and that the delayed wound-healing conditions created were more efficient to test our hypothesis than those used in previous studies [21] , [22] .…”

“…Because of these characteristics, ASCs have recently become a prime candidate for the repair of damaged tissue and other regenerative medicine applications [18] , [19] , [20] . Several experimental studies have reported that local injections of homogenous ASC suspensions improve the healing of intestinal anastomotic sites [21] , [22] .…”

Wound healing and fibrosis: current stem cell therapies

“…Ischemia can also increase the risk of stricture development in the bowel. Transplantation of ASCs and MSCs into the bowel wall in an ischemic colonic anastomosis rat model showed improved anastomotic healing with higher bowel bursting pressure, as well as decreased strictures, ulceration, and morbidity . Fistulas may also arise in the setting of IBD.…”

Effects of adipose stem cell sheets on colon anastomotic leakage in an experimental model: Proof of principle

“…The beneficial characteristics of ASCs could be exploited to promote the healing process in the intestinal wall after surgery, thus helping to prevent postoperative complications. Recent studies using intraperitoneal ASC injections or ASC-coated bio-sutures showed no prevention from anastomotic leakage [9,10]. Injection of ASCs as suspension or combined with biomaterials such as fibrin, collagen or gelatin is either associated with cell washout, insufficient cell retention or an inadequate distribution of transplanted cells.…”