鼠 Flk-1+Sca-1- 间充质干细胞：体外功能可塑性和体内免疫调节作用。

Mouse Flk-1+Sca-1- mesenchymal stem cells: functional plasticity in vitro and immunoregulation in vivo.

机构信息

1 Institute of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China. 2 Institute of Basic medicine, Peking Union Medical College, Department of Cell Biology, Beijing 100005, China. 3 Address correspondence to: Ren Jun, Ph.D., M.D., Institute of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

出版信息

Transplantation. 2014 Mar 15;97(5):509-17. doi: 10.1097/01.TP.0000442775.46133.38.

DOI:10.1097/01.TP.0000442775.46133.38

PMID:24487394

Abstract

OBJECTIVES

Mesenchymal stem cells (MSCs) represent a powerful tool in regenerative medicine because of their differentiation and migration capacities. Moreover, the immunomodulatory ability of MSCs may be used to develop therapies for the treatment of autoimmune diseases.

METHODS

In this study, we isolated Flk-1Sca-1 MSCs from bone marrow (bMSCs). Next, we studied their biological characteristics and immunologic functions. We also investigated their effects on graft-versus-host disease (GVHD) associated with allogeneic bone marrow transplantation in mice.

RESULTS

Flk-1Sca-1 bMSCs were able to differentiate into fat and cartilage cells, indicating that the isolated cells had stem cell properties. They could also suppress alloantigen-induced T cell proliferation in vitro in a dose-dependent manner. Infusion of bMSCs into allogeneic bone marrow-transplanted mice alleviated the lethal GVHD that occurred in control recipient mice. There was significantly lower mortality among the recipients of the Flk-1Sca-1 bMSCs that also ameliorated the clinical symptoms and GVHD histopathology. Beneficial effects on GVHD by Flk-1Sca-1 bMSCs were also observed when MSCs were engineered to express anti-inflammatory cytokines IL-4 and IL-10 and decrease expression of proinflammatory cytokines IFN-γ, TNF-α, and IL-2.

CONCLUSION

Flk-1Sca-1 bMSCs have stem cell properties and can efficiently ameliorate the GVHD associated with allogeneic bone marrow transplantation in mice.

摘要

目的

间充质干细胞（MSCs）因其分化和迁移能力而成为再生医学的有力工具。此外，MSCs 的免疫调节能力可用于开发治疗自身免疫性疾病的疗法。

方法

在这项研究中，我们从骨髓（bMSCs）中分离出 Flk-1Sca-1 MSCs。接下来，我们研究了它们的生物学特性和免疫功能。我们还研究了它们对同种异体骨髓移植相关移植物抗宿主病（GVHD）的影响。

结果

Flk-1Sca-1 bMSCs 能够分化为脂肪细胞和成软骨细胞，表明分离的细胞具有干细胞特性。它们还可以在体外以剂量依赖性方式抑制同种抗原诱导的 T 细胞增殖。将 bMSCs 输注到同种异体骨髓移植的小鼠中，减轻了对照受体小鼠发生的致命性 GVHD。Flk-1Sca-1 bMSCs 的受体小鼠死亡率明显降低，临床症状和 GVHD 组织病理学也得到改善。当将 MSC 工程改造为表达抗炎细胞因子 IL-4 和 IL-10 并降低促炎细胞因子 IFN-γ、TNF-α 和 IL-2 的表达时，Flk-1Sca-1 bMSCs 对 GVHD 也有有益的影响。