Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-3-22
pubmed:abstractText
Tolerance induction toward allogeneic organ grafts represents one of the major aims of transplantation medicine. Stem cells are promising candidates for promoting donor-specific tolerance. In this study, we investigated the immunomodulatory properties of murine embryonic stem cells (ESCs), obtained either by in vitro fertilization (IVF-ESCs) or by nuclear transfer (NT-ESCs), in heart transplant mouse models. IVF-ESCs did not prolong the survival of fully allogeneic cardiac transplants but significantly prolonged the survival of semiallogeneic hearts from the same ESC donor strain for >100 d in 44% of the animals. However, 28% of transplanted animals infused with IVF-ESCs experienced development of a teratoma. NT-ESCs similarly prolonged semiallogeneic heart graft survival (>100 d in 40% of the animals) but were less teratogenic. By in vitro studies, IVF-ESC and NT-ESC immunoregulation was mediated both by cell contact-dependent mechanisms and by the release of soluble factors. By adding specific inhibitors, we identified PGE(2) as a soluble mediator of ESC immunoregulation. Expansion of regulatory T cells was found in lymphoid organs and in the grafts of IVF-ESC- and NT-ESC-tolerized mice. Our study demonstrates that both IVF-ESCs and NT-ESCs modulate recipient immune response toward tolerance to solid organ transplantation, and that NT-ESCs exhibit a lower tendency for teratoma formation. Because NT-ESCs are obtained by NT of a somatic cell from living individuals into an enucleated oocyte, they could represent a source of donor-derived stem cells to induce tolerance to solid organ allograft.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4164-74
pubmed:meshHeading
pubmed-meshheading:21389254-Adoptive Transfer, pubmed-meshheading:21389254-Animals, pubmed-meshheading:21389254-Cell Line, pubmed-meshheading:21389254-Embryonic Stem Cells, pubmed-meshheading:21389254-Female, pubmed-meshheading:21389254-Fertilization in Vitro, pubmed-meshheading:21389254-Graft Rejection, pubmed-meshheading:21389254-Graft Survival, pubmed-meshheading:21389254-Heart Transplantation, pubmed-meshheading:21389254-Male, pubmed-meshheading:21389254-Mice, pubmed-meshheading:21389254-Mice, Inbred BALB C, pubmed-meshheading:21389254-Mice, Inbred C3H, pubmed-meshheading:21389254-Mice, Inbred C57BL, pubmed-meshheading:21389254-Mice, Inbred DBA, pubmed-meshheading:21389254-Mice, Transgenic, pubmed-meshheading:21389254-Nuclear Proteins, pubmed-meshheading:21389254-Random Allocation, pubmed-meshheading:21389254-Transplantation, Homologous
pubmed:year
2011
pubmed:articleTitle
Embryonic stem cells, derived either after in vitro fertilization or nuclear transfer, prolong survival of semiallogeneic heart transplants.
pubmed:affiliation
Department of Molecular Medicine, Mario Negri Institute for Pharmacological Research, Bergamo 24125, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't