Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-11-12
pubmed:abstractText
Although mesenchymal stromal cells (MSCs) exhibit marked immunoregulatory activity through multiple mechanisms, their potential to completely evade rejection upon transplantation into allogeneic recipients is controversial. To directly address this controversy, the survival of luciferase-labeled MSCs (Luc(+) MSCs) was evaluated by imaging in allogeneic recipients. This analysis showed that although MSCs exhibited longer survival compared to fibroblasts (Fib), their survival was significantly shorter compared to that exhibited in syngeneic or in immune-deficient Balb-Nude or non-obese diabetic severe combined immunodeficiency (NOD-SCID) recipients. Graft rejection in re-challenge experiments infusing Luc(+) Fib into mice, which had previously rejected Luc(+) MSCs, indicated potential induction of immune memory by the MSCs. This was further analyzed in T-cell antigen receptor (TCR) transgeneic mice in which either CD4 TEA mice or CD8 T cells (2C mice) bear a TCR transgene against a specific MHC I or MHC II, respectively. Thus, following a re-challenge with MSCs expressing the cognate MHC haplotype, an enhanced percentage of 2C CD8(+) or TEA CD4(+) T cells exhibited a memory phenotype (CD122(+), CD44(+), and CD62L(low)). Collectively, these results demonstrate that MSCs are not intrinsically immune-privileged, and under allogeneic settings, these cells induce rejection, which is followed by an immune memory. Considering that the use of allogeneic or even a third party ("off the shelf") MSCs is commonly advocated for a variety of clinical applications, our results strongly suggest that long-term survival of allogeneic MSCs likely represents a major challenge.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2865-74
pubmed:dateRevised
2011-4-21
pubmed:meshHeading
pubmed-meshheading:19750539-Animals, pubmed-meshheading:19750539-CD4-Positive T-Lymphocytes, pubmed-meshheading:19750539-CD8-Positive T-Lymphocytes, pubmed-meshheading:19750539-Cell Movement, pubmed-meshheading:19750539-Cell Survival, pubmed-meshheading:19750539-Cells, Cultured, pubmed-meshheading:19750539-Female, pubmed-meshheading:19750539-Fibroblasts, pubmed-meshheading:19750539-Flow Cytometry, pubmed-meshheading:19750539-Immunohistochemistry, pubmed-meshheading:19750539-Male, pubmed-meshheading:19750539-Mesenchymal Stem Cell Transplantation, pubmed-meshheading:19750539-Mesenchymal Stem Cells, pubmed-meshheading:19750539-Mice, pubmed-meshheading:19750539-Mice, Inbred BALB C, pubmed-meshheading:19750539-Mice, Inbred NOD, pubmed-meshheading:19750539-Mice, Nude, pubmed-meshheading:19750539-Mice, SCID, pubmed-meshheading:19750539-Mice, Transgenic, pubmed-meshheading:19750539-Stromal Cells, pubmed-meshheading:19750539-T-Lymphocytes, pubmed-meshheading:19750539-Transplantation, Homologous
pubmed:year
2009
pubmed:articleTitle
Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells.
pubmed:affiliation
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't