Topical transplantation of mesenchymal stem cells accelerates gastric ulcer healing in rats

Abstract

Mesenchymal stem cells (MSCs), a subpopulation of adult somatic stem cells, are an attractive stem cell source in regenerative medicine because of their multipotentiality. We examined the effects of MSC transplantation on gastric ulcer healing. Putative MSCs, isolated from bone marrow aspirates of male rats by dish adherence and expanded in culture, were characterized by flow cytometry and reverse transcription-polymerase chain reaction. Gastric ulcers were induced by serosal application of acetic acid on the anterior wall of the stomach in female rats. Either MSCs (labeled with PKH67; 1x10(7) cells) or vehicle was injected into the gastric wall surrounding the ulcer. The healing process of the ulcer and the influence of anti-vascular endothelial growth factor (VEGF) antibody were examined. CD29-positive, CD90-positive, CD34-negative, and CD45-negative MSCs expressed mRNAs for VEGF and hepatocyte growth factor (HGF). The MSCs were transplantable to the gastric tissue surrounding the ulcer, where a majority of the engrafted cells were positive for vimentin. The transplantation significantly accelerated gastric ulcer healing compared with controls. The engrafted MSCs also expressed VEGF and HGF. Administration of anti-VEGF neutralizing antibody dose dependently reduced the MSC-induced promotion of ulcer healing. In conclusion, MSC transplantation accelerated gastric ulcer healing, possibly through the induction of angiogenesis in the gastric mucosa via the secretion of VEGF. The beneficial effects of MSCs might be mediated not only by their differentiation into gastric interstitial cells, but also by their ability to supply angiogenic factors.

Epicardial Placement of Mesenchymal Stromal Cell-sheets for the Treatment of Ischemic Cardiomyopathy; In Vivo Proof-of-concept Study

“…After 3 weeks incubation, cells were fixed with 4% paraformaldehyde, and stained with Oil red O (Fluka) for detecting adipocytes containing lipid vacuoles or with Alizarin red (Fluka) to detect osteocytes containing calcium deposits. 9,31 All results of these characterisations (Supplementary Figure S5) consistently demonstrated that the collected cells were MSCs.…”

“…9,31 Adipogenic differentiation medium was α-minimal essential medium supplemented with 100 μmol/l isobutyl methylxathine (SigmaAldrich, Dorset, UK), 60 μmol/l indomethacin (Fluka, Dorset, UK), 1 μg/ml insulin (Sigma-Aldrich), and 0.5 μmol/l hydrocortisone (SigmaAldrich). Osteogenic differentiation medium was α-minimal essential medium supplemented with 0.1 μmol/l dexamethasone, 10 mmol/l β-glycerophosphate, and 0.05 mmol/l ascorbic acid (all from SigmaAldrich).…”

VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

“…Some studies have shown that MSCs could also achieve the biological effects by secreting VEGF. VEGF secreted by MSCs has been used in gastric ulcer and oral ulcer healing (El-Menoufy et al 2010;Hayashi et al 2008), in murine ischemic limbs leading to an increase in vessel density (Hoffmann et al 2010), in inhibiting the apoptosis of lung cells (Zhen et al 2010), in facilitating neurological function (Deng et al 2010), enhancing the repair and regeneration of critical sized bone defects (Kanczler et al 2010) and improving cardiac function in failing rat hearts (Tao et al 2009). Therefore, the VEGF 165 gene is the best target gene in gene therapy for promoting angiogenesis.…”

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

“…Improvements in liver function found in the previously mentioned studies seem not to be mainly mediated by parenchymal cell replacement, but by paracrine mechanisms promoting survival of endogenous hepatocytes and proliferation of hepatocyte progenitors. 188,230 MSCs could therefore exert their effects through secretion of cytokines 123,232 and growth factors, such as HGF 185 or nerve growth factor. 233 While the former can trigger hepatocyte anti-apoptotic mechanisms, 234 or inhibition of fibrogenesis by exportation of Smad3, 235 the latter might result in HeSC programmed cell death.…”