{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T17:08:10Z","timestamp":1786208890641,"version":"build-2736575974"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T00:00:00Z","timestamp":1471996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>Bone marrow (BM) is a reservoir for immune and hematopoietic cells and critical for tissue repair and regeneration. All of these functions are severely altered in cirrhosis. We investigated the cellular and functional state of BM in cirrhosis patients. We studied the histological, cellular, and molecular changes in BM of cirrhosis patients (n = 168) and controls (n = 44). Hematopoietic stem cells (HSCs) and associated niche cells, mesenchymal stem cells, Schwann cells, neural fibers, and endothelial cells were evaluated by immunohistochemistry. Cytokines and growth factors were analyzed in peripheral blood and BM plasma. Cirrhotic BM showed an inverse correlation between cluster of differentiation 34+HSCs and Model of End\u2010Stage Liver Disease (<jats:italic toggle=\"yes\">\u03c1<\/jats:italic> = \u20100.582, <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001) and Child's scores (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.038). BMs of cirrhosis patients with higher Model of End\u2010Stage Liver Disease (&gt;15) showed significantly decreased HSCs, mesenchymal stem cells, Schwann cells, and neural fibers; increased interleukin\u20101\u03b2 (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.004), tumor necrosis factor\u2010\u03b1 (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.040), and interferon\u2010\u03b3 (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.03); and decreased oncostatin M (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.04), stem cell factor (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.05), and stromal cell\u2010derived factor 1 (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.03) compared to those with lower Model of End\u2010Stage Liver Disease scores (\u226415). The cluster of differentiation 34+ cell population was a predictor for the development of sepsis (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001), and per unit loss increased the probability of sepsis by 16%. Cirrhosis patients with fewer HSCs had lower hemoglobin (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.05) and platelet counts (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.05) and showed early graft dysfunction. <jats:italic toggle=\"yes\">Conclusions:<\/jats:italic> Increasing severity of cirrhosis causes derangement of the hematopoietic niche and loss of HSCs, contributing to the hematological and immunological dysfunctions and reduced potential for regeneration; restoring BM functions could provide new therapeutic options in cirrhosis. (H<jats:sc>epatology<\/jats:sc> 2016;64:1273\u20101288)<\/jats:p>","DOI":"10.1002\/hep.28754","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T15:36:56Z","timestamp":1470238616000},"page":"1273-1288","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":57,"title":["Bone marrow stem cells and their niche components are adversely affected in advanced cirrhosis of the liver"],"prefix":"10.1097","volume":"64","author":[{"given":"Chhagan","family":"Bihari","sequence":"first","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovkesh","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetalnath","family":"Rooge","sequence":"additional","affiliation":[{"name":"Department of Research (Cellular and Molecular Medicine),Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhananjay","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Research (Cellular and Molecular Medicine),Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smriti","family":"Shubham","sequence":"additional","affiliation":[{"name":"Department of Research (Cellular and Molecular Medicine),Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Sukriti","sequence":"additional","affiliation":[{"name":"Department of Research (Cellular and Molecular Medicine),Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirupma","family":"Trehanpati","sequence":"additional","affiliation":[{"name":"Department of Research (Cellular and Molecular Medicine),Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guresh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Clinical Research,Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viniyendra","family":"Pamecha","sequence":"additional","affiliation":[{"name":"Department of Liver Transplant & Hepato\u2010pancreatico\u2010biliary Surgery,Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shvetank","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Research (Cellular and Molecular Medicine),Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Rastogi","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Research (Cellular and Molecular Medicine),Institute of Liver and Biliary Sciences,Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv K.","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,Delhi,India"},{"name":"Department of Research (Cellular and 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