Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of VIP Medical Center, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Mol Imaging Biol. 2018 Jun;20(3):417-427. doi: 10.1007/s11307-017-1128-0.
The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF).
Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology.
The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology.
The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.
本研究旨在探讨双重磁共振成像(MRI)报告基因(包括铁蛋白重链(Fth)和转铁蛋白受体(TfR))的可行性,这些基因可为体内 MRI 跟踪提供足够的 MRI 对比,以及 Deltex-1(DTX1)基因的可行性,该基因可促进人骨髓间充质干细胞(hMSC)向平滑肌细胞(SMC)分化,从而治疗闭合性阴茎骨折(CPF)。
生成多基因共表达 hMSC。评估 mRNA 和蛋白质的表达,并确定和比较 hMSC 的原始生物学特性。评估细胞内铁摄取,并检测向 SMC 分化的能力。50 只 CPF 兔随机接受 PBS、hMSC、Fth-TfR-hMSC、DTX1-hMSC 和 Fth-TfR-DTX1-hMSC 移植。进行体内 MRI 以检测移植细胞的分布和迁移以及 CPF 的愈合进展,并将结果与组织学相关联。
多基因的 mRNA 和蛋白质高度表达。转基因不会影响 hMSC 的原始生物学特性。双重 MRI 报告基因增加了铁积累能力,而 DTX1 基因促进 hMSC 向 SMC 分化。MRI 可明显检测到双重 MRI 报告基因修饰的 hMSC 的分布和迁移,以及 CPF 的愈合状态,并通过组织学得到证实。
双重 MRI 报告基因可提供足够的 MRI 对比,并可在体内检测 MSC 的分布和迁移。DTX1 基因可促进 MSC 向 SMC 分化,从而治疗 CPF,并有效抑制肉芽组织形成。