{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:03:25Z","timestamp":1784567005870,"version":"3.55.0"},"reference-count":75,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2011,7,18]]},"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Reports on the effects of bone marrow-derived cells on hepatic fibrosis are contradictory. Impaired fibrosis but increased inflammation has recently been demonstrated 10\u2005weeks after bone marrow transplantation (BM-Tx) in\n                      <jats:italic>Abcb4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. It is hypothesised that BM-Tx might have long-term therapeutic potential by altering the immunological and matrix remodelling processes leading to hepatic regeneration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      After lethal irradiation of recipient mice, BM cells from GFP+ donor mice (allogeneic Tx) or\n                      <jats:italic>\n                        Abcb4\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice (syngeneic Tx) were transplanted via tail vein injection. Readouts were performed 2, 10 and 20\u2005weeks after Tx. Liver integrity was assessed serologically and histologically. Surrogate markers for fibrogenesis, T helper (Th) response, inflammation, graft-versus-host disease and fibrolysis were analysed by quantitative real-time PCR, zymography and immunohistology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>20\u2005weeks after syngeneic and allogeneic BM-Tx, hepatic grading and staging were significantly improved. In contrast, 2\u2005weeks after BM-Tx inflammatory grading, expression of inflammatory cell markers and associated chemokines and their receptors were increased and subsequently declined. In parallel, CD8+\/GFP+ donor-derived T cells infiltrated the liver 2\u2005weeks after BM-Tx. The Th1 cyokine interferon \u03b3 was increased 2 and 10\u2005weeks after BM-Tx whereas the Th2 associated interleukin 13 was not altered. The gene expression of matrix metalloproteinases MMP-2, MMP-7, MMP-9 and MMP-13 was transiently upregulated and MMP-9 protein remained elevated 20\u2005weeks after BM-Tx with enhanced gelatinase activity located within the fibrotic areas. Neutrophils were identified as major sources of MMP-9.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results show that BM-Tx causes an antifibrotic Th1 response combined with transient inflammatory effects and subsequently upregulated MMP activity. Antifibrotic Th polarisation and prolonged proteolytic activity, especially of MMP-9, might be responsible for long-term amelioration of hepatic fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2011-300608","type":"journal-article","created":{"date-parts":[[2011,8,25]],"date-time":"2011-08-25T21:50:49Z","timestamp":1314309049000},"page":"907-916","source":"Crossref","is-referenced-by-count":41,"title":["Bone marrow transplantation improves hepatic fibrosis in\n                    <i>Abcb4<\/i>\n                    <sup>\u2212\/\u2212<\/sup>\n                    mice via Th1 response and matrix metalloproteinase 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