Department of Internal Medicine, CHA Stem Cell Institute, Seoul, Korea.
Acta Haematol. 2013;129(4):197-206. doi: 10.1159/000345267. Epub 2012 Dec 21.
Immunomodulatory properties of mesenchymal stem cells (MSCs) have been applied to reduce the incidence of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Among the various sources of MSCs that have immunomodulatory effects in vitro, only placenta-derived MSCs (PD-MSCs) have not been evaluated in an in vivo model of GVHD. In this study, we investigated the immunomodulatory properties of PD-MSCs in vitro and evaluated their clinical potential for controlling GVHD in an animal model.
A GVHD animal model was established by transplanting C57BL/6 donor bone marrow cells and spleen cells into lethally irradiated BALB/c recipient mice. To control GVHD, human PD-MSCs were transplanted into recipient mice (5 × 10(5) or 1 × 10(6) cells).
PD-MSCs suppressed mitogen-stimulated T cell proliferation in vitro in a dose-dependent manner. Moreover, PD-MSCs inhibited cytokine secretion (interleukin-12, tumor necrosis factor-α and interferon-γ) of activated T cells. In vivo, the survival rate in the PD-MSC group (transplanted with 1 × 10(6) cells) was higher than that in the control group and histological scores were low in the PD-MSC group.
We present the first evidence that human PD-MSCs can efficiently control GVHD in an HSCT in vivo model.
间充质干细胞(MSCs)的免疫调节特性已被应用于降低造血干细胞移植(HSCT)后移植物抗宿主病(GVHD)的发生率。在具有体外免疫调节作用的各种 MSC 来源中,只有胎盘来源的 MSC(PD-MSCs)尚未在 GVHD 的体内模型中进行评估。在这项研究中,我们研究了 PD-MSCs 的体外免疫调节特性,并评估了它们在动物模型中控制 GVHD 的临床潜力。
通过将 C57BL/6 供体骨髓细胞和脾细胞移植到致死性照射的 BALB/c 受体小鼠中,建立 GVHD 动物模型。为了控制 GVHD,将人 PD-MSCs 移植到受体小鼠中(5×10(5)或 1×10(6)个细胞)。
PD-MSCs 以剂量依赖的方式抑制有丝分裂原刺激的 T 细胞增殖。此外,PD-MSCs 抑制活化 T 细胞的细胞因子分泌(白细胞介素-12、肿瘤坏死因子-α和干扰素-γ)。在体内,PD-MSC 组(移植 1×10(6)个细胞)的存活率高于对照组,且 PD-MSC 组的组织学评分较低。
我们首次证明人 PD-MSCs 可有效控制 HSCT 体内模型中的 GVHD。