{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:53:16Z","timestamp":1760237596600,"version":"build-2065373602"},"reference-count":79,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seventh Framework Programme","award":["HEALTH-F2-2012-305736"],"award-info":[{"award-number":["HEALTH-F2-2012-305736"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Individuals living with type 1 diabetes mellitus may experience an increased risk of long bone fracture. These fractures are often slow to heal, resulting in delayed reunion or non-union. It is reasonable to theorize that the underlying cause of these diabetes-associated osteopathies is faulty repair dynamics as a result of compromised bone marrow progenitor cell function. Here it was hypothesized that the administration of non-diabetic, human adult bone marrow-derived mesenchymal stromal cells (MSCs) would enhance diabetic fracture healing. Human MSCs were locally introduced to femur fractures in streptozotocin-induced diabetic mice, and the quality of de novo bone was assessed eight weeks later. Biodistribution analysis demonstrated that the cells remained in situ for three days following administration. Bone bridging was evident in all animals. However, a large reparative callus was retained, indicating non-union. \u00b5CT analysis elucidated comparable callus dimensions, bone mineral density, bone volume\/total volume, and volume of mature bone in all groups that received cells as compared to the saline-treated controls. Four-point bending evaluation of flexural strength, flexural modulus, and total energy to re-fracture did not indicate a statistically significant change as a result of cellular administration. An ex vivo lymphocytic proliferation recall assay indicated that the xenogeneic administration of human cells did not result in an immune response by the murine recipient. Due to this dataset, the administration of non-diabetic bone marrow-derived MSCs did not support fracture healing in this pilot study.<\/jats:p>","DOI":"10.3390\/cells9061394","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T04:36:09Z","timestamp":1591245369000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Administration of Human Non-Diabetic Mesenchymal Stromal Cells to a Murine Model of Diabetic Fracture Repair: A Pilot Study"],"prefix":"10.3390","volume":"9","author":[{"given":"Luke","family":"Watson","sequence":"first","affiliation":[{"name":"Orbsen Therapeutics Ltd., Galway City H91 EFD0, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland Galway,  Galway City H91 W2TY, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aideen E.","family":"Ryan","sequence":"additional","affiliation":[{"name":"College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland Galway,  Galway City H91 W2TY, County Galway, Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, College of Medicine, Nursing and Health Sciences, School of Medicine, National University of Ireland Galway, Galway City  H91 W2TY, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ine","family":"Fleming","sequence":"additional","affiliation":[{"name":"College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland Galway,  Galway City H91 W2TY, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aoife","family":"Carbin","sequence":"additional","affiliation":[{"name":"College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland Galway,  Galway City H91 W2TY, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9054-0726","authenticated-orcid":false,"given":"Lisa","family":"O\u2019Flynn","sequence":"additional","affiliation":[{"name":"Orbsen Therapeutics Ltd., Galway City H91 EFD0, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul G.","family":"Loftus","sequence":"additional","affiliation":[{"name":"Orbsen Therapeutics Ltd., Galway City H91 EFD0, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Horan","sequence":"additional","affiliation":[{"name":"Orbsen Therapeutics Ltd., Galway City H91 EFD0, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Connolly","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, College of Science and Engineering, National University of Ireland Galway,  Galway City H91 HX31, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"McDonnell","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, College of Science and Engineering, National University of Ireland Galway,  Galway City H91 HX31, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laoise M.","family":"McNamara","sequence":"additional","affiliation":[{"name":"C\u00daRAM Centre for Research in Medical Devices, College of Medicine, Nursing and Health Sciences, School of Medicine, National University of Ireland Galway, Galway City  H91 W2TY, County Galway, Ireland"},{"name":"Biomedical Engineering, College of Science and Engineering, National University of Ireland Galway,  Galway City H91 HX31, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Orbsen Therapeutics Ltd., Galway City H91 EFD0, County Galway, Ireland"},{"name":"College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland Galway,  Galway City H91 W2TY, County Galway, Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, College of Medicine, Nursing and Health Sciences, School of Medicine, National University of Ireland Galway, Galway City  H91 W2TY, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia M.","family":"Coleman","sequence":"additional","affiliation":[{"name":"College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland Galway,  Galway City H91 W2TY, County Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF03343726","article-title":"Osteopenia in insulin-dependent diabetes mellitus; prevalence and aspects of pathophysiology","volume":"23","author":"Kemink","year":"2000","journal-title":"J. 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