title: Influence of mesenchymal stem cells on stomach tissue engineering using small intestinal submucosa.
abstract: Small intestinal submucosa (SIS) is a biodegradable collagen-rich matrix containing functional growth factors. We have previously reported encouraging outcomes for regeneration of an artificial defect in the rodent stomach using SIS grafts, although the muscular layer was diminutive. In this study, we investigated the feasibility of SIS in conjunction with mesenchymal stem cells (MSCs) for regeneration of the gastrointestinal tract. MSCs from the bone marrow of green fluorescence protein (GFP)-transgenic Sprague-Dawley (SD) rats were isolated and expanded ex vivo. A 1 cm whole-layer stomach defect in SD rats was repaired using: a plain SIS graft without MSCs (group 1, control); a plain SIS graft followed by intravenous injection of MSCs (group 2); a SIS graft co-cultured with MSCs (group 3); or a SIS sandwich containing an MSC sheet (group 4). Pharmacological, electrophysiological and immunohistochemical examination was performed to evaluate the regenerated stomach tissue. Contractility in response to a muscarinic receptor agonist, a nitric oxide precursor or electrical field stimulation was observed in all groups. SIS grafts seeded with MSCs (groups 3 and 4) appeared to support improved regeneration compared with SIS grafts not seeded with MSCs (groups 1 and 2), by enabling the development of well-structured smooth muscle layers of significantly increased length. GFP expression was detected in the regenerated interstitial tissue, with fibroblast-like cells in the seeded-SIS groups. SIS potently induced pharmacological and electrophysiological regeneration of the digestive tract, and seeded MSCs provided an enriched environment that supported tissue regeneration by the SIS graft in the engineered stomach.
authors.affiliation: Department of Digestive Surgery and Surgical Oncology (Department of Surgery II), Yamaguchi University Graduate School of Medicine, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakatsu
authors.forename: Tomio
authors.initials: T
authors.lastname: Ueno
authors.forename: Atsunori
authors.initials: A
authors.lastname: Oga
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakao
authors.forename: Taku
authors.initials: T
authors.lastname: Nishimura
authors.forename: Sei
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D000818:Animals; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D044968:Regenerative Medicine; D013270:Stomach / Q000166:cytology; D023822:Tissue Engineering
keywords: GFP; SIS; extracellular matrix; mesenchymal stem cell; small intestinal submucosa; stomach tissue engineering
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