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Flk-1⁺Sca-1⁻间充质干细胞:体外功能特性及体内再生能力

Flk-1⁺Sca-1⁻ mesenchymal stem cells: functional characteristics in vitro and regenerative capacity in vivo.

作者信息

Li Yugang, Pan Enshan, Wang Yu, Zhu Xiaoguang, Wei Anyang

机构信息

Hospital of Integrated Traditional Chinese Medicine & Western Medicine, Southern Medical University Guangzhou 510315, China.

Department of Urology, Medical Center for Overseas Patients, Nanfang Hospital, Southern Medical University Guangzhou 510515, China.

出版信息

Int J Clin Exp Pathol. 2015 Sep 1;8(9):9875-88. eCollection 2015.

Abstract

OBJECTIVES

Mesenchymal stem cells (MSCs) represent a powerful tool in regenerative medicine because of their differentiation and migration capacities. We aimed to investigate the possibility of Flk-1(+)Sca-1(-) mesenchymal stem cells (Flk-1(+)Sca-1(-) MSCs) transplantation to repair erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED).

METHODS

In this study, we isolated Flk-1(+)Sca-1(-) MSCs from bone marrow (bMSCs). Then, newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine for the purpose of tracking endogenous Flk-1(+)Sca-1(-) MSCs. Eight weeks later, 8 of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group) while another 8 rats were subject to Flk-1(+)Sca-1(-) MSCs treatment (DM+MSC group). All rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology.

RESULTS

Flk-1(+)Sca-1(-) MSCs could differentiate into skeletal muscle cells and endothelial cells in vivo and in vitro. Engrafted Flk-1(+)Sca-1(-) MSCs were shown to home to injured muscle, participate in myofibers repair and could partially reconstitute the sarcolemmal expression of myocardin and ameliorate the level of related specific pathological markers.

CONCLUSION

Flk-1(+)Sca-1(-) MSCs could be used in the treatment erectile function in diabetes mellitus associated erectile dysfunction by promoting regeneration of nNOS-positive nerves, endothelium, and smooth muscle in the penis.

摘要

目的

间充质干细胞(MSCs)因其分化和迁移能力,成为再生医学中的有力工具。我们旨在研究Flk-1(+)Sca-1(-)间充质干细胞(Flk-1(+)Sca-1(-) MSCs)移植修复糖尿病(DM)相关勃起功能障碍(ED)患者勃起功能的可能性。

方法

在本研究中,我们从骨髓(bMSCs)中分离出Flk-1(+)Sca-1(-) MSCs。然后,为追踪内源性Flk-1(+)Sca-1(-) MSCs,对新生雄性大鼠腹腔注射5-乙炔基-2'-脱氧尿苷。八周后,随机选取其中8只大鼠作为正常对照(N组)。其余大鼠腹腔注射60 mg/kg链脲佐菌素(STZ)诱导DM。随机选取其中8只大鼠作为DM对照(DM组),另外8只大鼠接受Flk-1(+)Sca-1(-) MSCs治疗(DM+MSC组)。通过海绵体内压(ICP)测量评估所有大鼠的勃起功能。之后,对其阴茎组织进行组织学检查。

结果

Flk-1(+)Sca-1(-) MSCs在体内和体外均可分化为骨骼肌细胞和内皮细胞。移植的Flk-1(+)Sca-1(-) MSCs显示可归巢至损伤肌肉,参与肌纤维修复,并可部分重建肌动蛋白相关蛋白的肌膜表达,改善相关特异性病理标志物水平。

结论

Flk-1(+)Sca-1(-) MSCs可通过促进阴茎中nNOS阳性神经、内皮和平滑肌的再生,用于治疗糖尿病相关勃起功能障碍的勃起功能。

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