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Direct Imaging of Immune Rejection and Memory Induction by Allogeneic Mesenchymal Stromal Cells
- Source :
- Stem Cells. 27:2865-2874
- Publication Year :
- 2009
- Publisher :
- Oxford University Press (OUP), 2009.
-
Abstract
- 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 CD62Llow). 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. Disclosure of potential conflicts of interest is found at the end of this article.
- Subjects :
- CD4-Positive T-Lymphocytes
Male
Cell Survival
T-Lymphocytes
Mice, Nude
Mice, Transgenic
Mice, SCID
CD8-Positive T-Lymphocytes
Biology
Mesenchymal Stem Cell Transplantation
Major histocompatibility complex
Cell therapy
Mice
Cell Movement
Mice, Inbred NOD
MHC class I
medicine
Animals
Transplantation, Homologous
Cytotoxic T cell
Cells, Cultured
Mice, Inbred BALB C
Severe combined immunodeficiency
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Fibroblasts
Flow Cytometry
medicine.disease
Immunohistochemistry
Transplantation
Immunology
biology.protein
Molecular Medicine
Female
Stromal Cells
CD8
Developmental Biology
Subjects
Details
- ISSN :
- 15494918 and 10665099
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Stem Cells
- Accession number :
- edsair.doi.dedup.....6ac4385a7a03c513cb4da9967ec765f4