Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft.
BACKGROUND
Mesenchymal stem cells (MSCs) are multipotent adult elements that have recently been shown to have profound immunomodulatory effects both in vitro and in vivo. Herein we have examined the impact of intravenous infusion of donor MSCs on the survival of transplanted hearts in a rat allograft model.


METHODS
Recipient Fisher344 rats were transplanted with hearts from inbred Wistar rats. Wistar rat MSCs were infused via the tail vein at designated intervals. In vitro mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays were performed to assess whether MSCs downregulated T-cell responses in vivo. Real-time polymerase chain reaction (PCR) was used to analyze the Th1/Th2 balance in MSC-treated and control groups.


RESULTS
The MSCs cultured in vitro exhibited multipotential for differentiation. Survival of the allografts was markedly prolonged by administration of MSCs compared with the controls, namely mean survivals of 12.4 vs 6.4 days, respectively. Real-time PCR showed a shift in the Th1/Th2 balance toward Th2. By MLR and CML assays, untreated control rats showed greater alloreactivity than did MSC-treated rats.


CONCLUSIONS
Our results indicated that MSCs suppressed allogeneic T-cell responses both in vitro and in vivo. Intravenous administration of MSCs prolonged the survival of transplanted hearts, possibly by induction of allograft tolerance through changing the Th1/Th2 balance.
Zhou
H P
HP
Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an City, Shannxi Province, China. zhp1977@fmmu.edu.cn
Yi
D H
DH
Yu
S Q
SQ
Sun
G C
GC
Cui
Q
Q
Zhu
H L
HL
Liu
J C
JC
Zhang
J Z
JZ
Wu
T J
TJ
D000818:Animals; D018929:Cell Culture Techniques; D017931:DNA Primers; D006085:Graft Survival / Q000502:physiology*; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007959:Lymphocyte Culture Test, Mixed; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous / Q000276:immunology / Q000502:physiology
D017931:DNA Primers; D007375:Interleukin-1; D016753:Interleukin-10; D007371:Interferon-gamma