Human placental stem cell-based therapies for prevention of abdominal adhesions: A prospective randomized preclinical trial.

BACKGROUND: Abdominal adhesions are networks of fibrotic tissues that form between organs postoperatively. Current prophylactic strategies do not reproducibly prevent adhesive small bowel obstruction across the entire abdomen. Human placental-derived stem cells produce an anti-inflammatory secretome that has been applied to multiple fibrosing diseases. The purpose of this project is to test human placental stem cell (hPSC)-based therapies for prevention of abdominal adhesions in a clinically relevant rat model. METHODS: Fifty-four (n = 54, n = 6/group) male Sprague-Dawley rats (250-350 g) underwent model creation and treatment randomization under anesthesia. Experimental groups included human placental-derived stem cells (hPSC, 5 × 106 cells/10 mL Plasmalyte A), human placental-derived stem cells in a hyaluronic acid (HA-Mal-hPSC) hydrogel, the human placental-derived stem cell secretome from conditioned media in 10 mL Plasmalyte A, human placental-derived stem cells' conditioned media in a hyaluronic acid (HA-Mal-CM) hydrogel, Plasmalyte A (media alone, 10 mL), hyaluronic acid hydrogel alone (HA-Mal), Seprafilm (Baxter, Deerfield, IL), and the control groups, model with no treatment (MNT) and sham animals. Treatments were administered intraperitoneally, and the study period was 14 days postoperation. Adhesions were scored at necropsy and analyzed as the difference between means of an index statistic (Animal Index Score) versus MNT. Underlying molecular mechanisms were explored by functional genomic analysis and histology of peritoneal tissues. RESULTS: Hyaluronic acid hydrogel alone, HA-Mal-CM hydrogel, and Seprafilm significantly reduced the overall appearance of abdominal adhesions by mean Animal Index Score at 14 days versus MNT. Human placental stem cell, HA-Mal-hPSC hydrogel, HA-Mal-CM hydrogel, HA-Mal hydrogel alone, and Seprafilm significantly reduced the collagen content of injured peritoneal tissues. Human placental stem cell and HA-Mal-hPSC hydrogel suppressed expression of the most profibrotic genes. Conditioned media, HA-Mal hydrogel alone, and media alone significantly altered the expression of proteins associated with peritoneal fibrotic pathways. CONCLUSION: Human placental stem cell-based therapies reduce abdominal adhesions in a prospective randomized preclinical trial. This effect is supported by suppression of profibrotic genomic and proteomic pathways.