Linked Life Data

18564903

Source:http://linkedlifedata.com/resource/pubmed/id/18564903

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-4-20
pubmed:abstractText
Acute kidney injury (AKI) is a major clinical problem associated with high morbidity and mortality. Likely due to its complex pathophysiology, therapies with a single pharmacological agent have generally failed to improve outcomes. In contrast, stem cell-based interventions utilize these cells' ability to simultaneously target multiple pathophysiological components of AKI and thus represent a promising new tool for the treatment of AKI. The aims of the this study were to investigate the long-term outcome and safety of treatment with autologous and allogeneic mesenchymal stem cells (MSCs) after AKI and the role of vascular endothelial growth factor (VEGF) as one of the principal paracrine mediators of renoprotection of MSCs. MSC administration after AKI was not associated with adverse events and proved to be renoprotective in animals with severe renal failure. Identical doses of autologous MSC were more effective than allogeneic. At 3 months, MSCs were not engrafted in any tissues except in the bone marrow in 50% of animals given the highest allogeneic cell dose. There was no long-term fibrotic response in the kidneys attributable to MSC therapy, and animals with severe AKI were protected from development of fibrotic lesions after AKI. Furthermore, this study establishes VEGF as a critical factor mediating renal recovery. VEGF knockdown by small-interfering RNA reduced effectiveness of MSCs significantly and decreased survival. In summary, our results show that both autologous and allogeneic MSC are safe and effective in AKI, and importantly, reduce late renal fibrosis and loss of renal function in surviving animals and that VEGF is a critical factor in renoprotection by MSCs. Together, we posit that these data provide further justification for the conduct of clinical trails in which AKI is treated with MSC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1557-8534
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
475-85
pubmed:dateRevised
2011-10-25
pubmed:meshHeading
pubmed-meshheading:18564903-Acute Kidney Injury, pubmed-meshheading:18564903-Animals, pubmed-meshheading:18564903-Bone Marrow Cells, pubmed-meshheading:18564903-Gene Expression, pubmed-meshheading:18564903-Humans, pubmed-meshheading:18564903-Kidney, pubmed-meshheading:18564903-Male, pubmed-meshheading:18564903-Plasminogen Activator Inhibitor 1, pubmed-meshheading:18564903-RNA, Small Interfering, pubmed-meshheading:18564903-Rats, pubmed-meshheading:18564903-Rats, Inbred F344, pubmed-meshheading:18564903-Rats, Sprague-Dawley, pubmed-meshheading:18564903-Rats, Transgenic, pubmed-meshheading:18564903-Stem Cell Transplantation, pubmed-meshheading:18564903-Stromal Cells, pubmed-meshheading:18564903-Transforming Growth Factor beta, pubmed-meshheading:18564903-Transplantation, Autologous, pubmed-meshheading:18564903-Transplantation, Homologous, pubmed-meshheading:18564903-Vascular Endothelial Growth Factor A
pubmed:year
2009
pubmed:articleTitle
Autologous and allogeneic marrow stromal cells are safe and effective for the treatment of acute kidney injury.
pubmed:affiliation
Department of Medicine, Division of Nephrology, University of Utah, Salt Lake City, Utah 84148, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural