人类间充质干细胞成瘤过程中运动及迁移能力的变化

目的 研究人类间充质干细胞（hMSC）成瘤过程中细胞运动能力及迁移能力的变化.方法 依次应用人端粒酶逆转录酶（hTERT）、SV40 T抗原（SV40 TAg）及癌基因H-Ras V12转染hMSC成瘤,应用划痕愈合实验及Boyden小室实验分别检测成瘤过程中不同转化细胞的自由迁移和趋触性的改变.结果 hMSC成功转化为两种不同表型的恶性肿瘤细胞.细胞的自由迁移能力在全部成瘤过程中没有发生明显改变.转染RAS后,细胞的趋触性有明显增加.结论 癌基因RAS可明显增加hMSC的迁移能力,永生化的hMSC在细胞运动能力方面相对安全.     

Lithium doped silica nanospheres/poly(dopamine) composite coating on polyetheretherketone to stimulate cell responses,improve bone formation and osseointegration

Osseointegration is crucial for early fixation as well as long-term success of orthopedic implants. Bioactive composite containing lithium doping silica nanospheres (LSNs) and poly(dopamine) (PDA) were coated on polyetheretherketone (PK) surface (LPPK), and effects of the LSNs/PDA composite (LPC) coating on the biological properties of LPPK were assessed both in vitro and in vivo. Results showed that LPPK with improved bioactivity remarkably promoted apatite mineralization in simulated body fluid (SBF) compared with PDA coated on PK (PPK) and PK. Moreover, the LPPK remarkably stimulated rat bone marrow stromal cells (rBMSCs) responses compared with PPK and PK. Furthermore, the LPPK significantly promoted bone tissues responses in vivo compared with PPK and PK. It could be suggested that the improvements of cells and bone tissues responses were attributed to the surface characteristics of the bioactive LPC coating on LPPK. The LPPK would be a great candidate for orthopedic and dental applications.     

The interplay of T1- and T2-relaxation on T1-weighted MRI of hMSCs induced by Gd-DOTA-peptides

Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized and used as T₁ contrast agent to label human mesenchymal stem cells (hMSCs) for magnetic resonance imaging study. The peptides include a universal cell penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC-specific peptide CC9. A significant difference in labeling efficacy is observed between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides as well as Dotarem induce significant increase in T₁ relaxation rate which is in favor of T₁-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy but poor T₁ contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling efficacy but better T₁ contrast enhancement. Gd-DOTA-TAT yields a similar labeling efficacy as Gd-DOTA-CC9 and similar T₁ contrast enhancement as Gd-DOTA-EM7. The underlying mechanism that governs T₁ contrast enhancement effect is discussed. Our results suggest that T₁ contrast enhancement induced by Gd-DOTA-peptides depends not only on the introduced cellular Gd content, but more importantly on the effect that Gd-DOTA-peptides exert on the T₁-relaxation and T₂-relaxation processes/rates. Both T₁ and particularly T₂ relaxation rate have to be taken into account to interpret T₁ contrast enhancement. In addition, the interpretation has to be based on cellular instead of aqueous longitudinal and transverse relaxivities of Gd-DOTA-peptides.     

Hepatogenic engineering from human bone marrow mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture

Bone marrow mesenchymal stem cells (MSCs) are promising candidates for cell therapy and tissue engineering. We used mesenchymal stem cells from human bone marrow (hMSCs) as the seeding cells to investigate the potential of hepatocytic differentiation of hMSCs in porous polylactic glycolic acid (PLGA) scaffolds under perfusion induction. hMSCs were seeded and proliferated in PLGA scaffolds, and then induced into hepatocyte-like cells with hepatogenic medium in perfusion and static cultures. The results showed that hMSCs could be induced into hepatocyte-like cells in PLGA scaffolds with hepatogenic medium in both static and perfusion induction systems. However, perfusion induction was more effective for cellularity in PLGA scaffolds than in static induction. Cells in the scaffold induced by the hepatogenic medium expressed hepatocyte-specific genes cytokeratin 19 (CK19), α-fetoprotein (αFP), cytokeratin 18 (CK18), albumin and cytochrome P4503A4 (CYP3A4) in a time-dependent manner. Induced cells stained positive for αFP and albumin. Induced cells also acquired the functional characteristics of hepatocytes, i.e. secretion of urea and albumin. In a comparison of survival and hepatogenic differentiation of hMSCs between perfusion and static induction, perfusion induction increased the survival and the uniform distribution of induced cells in scaffolds, which resulted in a higher efficiency of hepatogenesis in the PLGA construct with hMSCs. The oscillatory perfusion induction system combined with the hepatogenic medium should be a valuable and convenient tool for in vitro hepatic tissue engineering using hMSCs.