Buron F, Perrin H, Malcus C, Héquet O, Thaunat O, Kholopp-Sarda M-N, Moulin F T, Morelon E
INSERM U 851 Lyon, Université Lyon1, Villeurbanne, France.
Transplant Proc. 2009 Oct;41(8):3347-52. doi: 10.1016/j.transproceed.2009.08.030.
The use of mesenchymal stem cells (MSC), which display immunosuppressive activity, seems to be a promising therapeutic approach in solid organ transplantation. However, little is known about their interactions with immunosuppressive drugs. The objective of this study was to assess these interactions in allogeneic responses.
We studied the effects on alloimmune responses in mixed lymphocyte reactions of MSC plus five agents-cyclosporine, tacrolimus, rapamycin, mycophenolate acid (MPA), and dexamethasone (DEX).
Human MSC isolated from bone marrow were characterized by their phenotype and their ability to differentiate into adipocytes or osteoblastes. MSC plus the agents inhibited allogeneic lymphocyte proliferation in a dose-dependent manner. Calcineurin inhibitors and rapamycin antagonized the inhibitory effect of MSC, whereas MPA promoted it and DXM did not modify it.
MPA seems to be the best immunosuppressant to associated with MSC for transplanted patients.
具有免疫抑制活性的间充质干细胞(MSC)的应用似乎是实体器官移植中一种很有前景的治疗方法。然而,关于它们与免疫抑制药物的相互作用却知之甚少。本研究的目的是评估在同种异体反应中的这些相互作用。
我们研究了MSC加五种药物——环孢素、他克莫司、雷帕霉素、霉酚酸(MPA)和地塞米松(DEX)对混合淋巴细胞反应中同种异体免疫反应的影响。
从骨髓中分离出的人MSC通过其表型以及分化为脂肪细胞或成骨细胞的能力进行表征。MSC加这些药物以剂量依赖的方式抑制同种异体淋巴细胞增殖。钙调神经磷酸酶抑制剂和雷帕霉素拮抗MSC的抑制作用,而MPA则促进其抑制作用,地塞米松未改变其抑制作用。
对于移植患者,MPA似乎是与MSC联合使用的最佳免疫抑制剂。