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New, pathogenesis‐based pharmacologic approaches to gastrointestinal ulcers: Gene therapy with egr‐1 & cell therapy with bone marrow‐derived stem cells
Author(s) -
Szabo Sandor,
Deng Xiaoming,
Chen Longchuan,
Khomenko Tetyana,
Sandor Zsuzsanna
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.663.8
Subject(s) - medicine , stem cell , bone marrow , angiogenesis , neovascularization , genetic enhancement , pathogenesis , pharmacology , endocrinology , cancer research , immunology , biology , gene , microbiology and biotechnology , biochemistry
Our recent studies showed that the immediate‐early gene early growth response (egr‐1) that regulates the expression of angiogenic growth factors (e.g., VEGF, bFGF, PDGF) & neovascularization play a mechanistic role in experimental duodenal ulceration (DU). We thus hypothesized that gene therapy with adenovirus (AV) encoding egr‐1 & local administration of bone marrow‐derived stem cells (BMSC) may accelerate the healing of both upper & lower gastrointestinal ulcers, i.e., DU & ulcerative colitis (UC). Groups of rats were given cysteamine‐HCl (C, 85 mg/100g, x1, gavage) to induce DU or 6% iodoacetamide (IA, 0.1ml/rat, x1, enema) to cause UC. A single dose of either AV‐egr‐1 (2 × 109 pfu/rat) or BMSC (1 × 106 cells/rat) was given intraduodenally at laparotomy in DU rats on the 3rd day after C or intracolonically in UC rats on the 2nd day after IA. The rats were euthanized on the 7th or 14th day after C or IA administration. We found that DU & UC lesion areas were significantly reduced in rats treated with AV‐egr‐1 or BMSC compared to controls in both 7 & 14 days (p < 0.05). Increased levels (2‐ to 4‐folds) of growth factors VEGF, PDGF and bFGF were also seen at days 7 and 14 in the rats treated with AV‐egr‐1 or BMSC compared to the controls. Conclusions local egr‐1 gene or stem cell therapies seem to be a new option to achieve a rapid healing of DU & UC, possibly by promoting angiogenesis/vasculogenesis & restoring mucosal integrity. (This work was supported by the Veterans Health Administration Merit Review Grants to S. Szabo and Zs. Sandor).