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 Blood, 1 January 2009, Vol. 113, No. 1, pp. 46-57.
Prepublished online as a Blood First Edition Paper on October 2, 2008; DOI 10.1182/blood-2008-04-154138.

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Submitted April 28, 2008
Accepted September 7, 2008

Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2 dependent regulatory dendritic cell population

Bin Zhang, Rui Liu, Dan Shi, Xingxia Liu, Yuan Chen, Xiaowei Dou, Xishan Zhu, Chunhua Lu, Wei Liang, Lianming Liao, Martin Zenke, and Robert C.H. Zhao*

Center of Excellence in Tissue Engineering, Department of Cell Biology, Institute of Basic Medical Sciences CAMS & School of Basic Medicine PUMC, Beijing, China
Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Aachen, Germany

* Corresponding author; email: chunhuaz{at}public.tpt.tj.cn.

Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, exert immunomodulatory effects on immune cells, even dendritic cells (DCs). However, whether they influence destiny of full mature DCs (maDCs) remains controversial. Here we report that MSCs vigorously promote proliferation of maDCs, significantly reduce their expression of Ia, CD11c, CD80, CD86 and CD40 while increase CD11b expression. Interestingly, though these phenotypes clearly suggest their skew to immature status, bacterial lipopolysaccharide (LPS) stimulation could not reverse this trend. Moreover, high endocytosic capacity, low immunogenicity and strong immunoregulatory function of MSC-treated maDCs (MSC-DCs) were also observed. Furthermore we found that MSCs, partly via cell-cell contact, drive maDCs to differentiate into a novel Jagged-2-dependent regulatory DC population and escape their apoptotic fate. These results further support the role of MSCs in preventing rejection in organ transplantation and treatment of autoimmune disease.


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