Mesenchymal stem cells (MSCs) have drawn great attention because of their therapeutic potential. It has been suggested that intra‐venous infused MSCs could migrate the site of injury to help repair the damaged tissue. However, the mechanism for MSC migration is still not clear so far. In this study, we reported that hypoxia increased chemotaxis migration of MSCs. At 4 and 6 hours after culturing in hypoxic (1% oxygen) conditions, the number of migrated MSCs was significantly increased. Meanwhile, hypoxia also increased the expression of HIF‐1α and SDF‐1. Using small interference RNA, we knocked down the expression of HIF‐1α in MSCs to study the role of HIF‐1α in hypoxia induced migration. Our data indicated that knocking down the expression of HIF‐1α not only abolished the migration of MSCs, but also reduced the expression of SDF‐1. Combining the results of migration assay and expression at RNA and protein level, we demonstrated a novel mechanism that controls the increase of MSCs migration. This mechanism involved HIF‐1α mediated SDF‐1 expression. These findings provide new insight into the role of HIF‐1α in the hypoxia induced MSC migration and can be a benefit for the development of MSC‐based therapeutics for wound healing.

Background: MicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied. Methods: We collected human osteosarcoma specimens and adjacent tissues to detect the expression of miR-16-5p by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. The proliferation, migration, and invasion of MG63 and HOS cells following miR-16-5p overexpression and inhibition were detected with cell counting kit-8, wound healing assay, and Transwell assay, respectively. An expression vector carrying a mutated 3′-untranslated region of mothers against decapentaplegic homolog 3 (Smad3) was constructed. Results: The results showed that miR-16-5p expression was downregulated in osteosarcoma tissues and cells as compared with adjacent counterparts, while Smad3 was overexpressed in osteosarcoma cells. The overexpression of miR-16-5p resulted in the inhibition of the proliferation, migration, and invasion of osteosarcoma cells and enhanced the therapeutic effect of cisplatin. These effects were attenuated with miR-16-5p expression inhibition. In cells transfected with miR-16-5p mimic, Smad3 expression decreased, while this effect was absent in the cells carrying mutated Smad3. Conclusions: Therefore, miR-16-5p inhibits the growth and invasion of osteosarcoma by targeting Smad3.

Although the cancer immunotherapy represents one of the most promising strategies for cancer treatment, the PD-1/PD-L1 pathway, which involves a receptor-ligand interaction, can induced immunosuppression by disabling tumor-infiltrating lymphocytes (TILs). In the present study, we coupled a PD-L1 (Programmed cell death 1 ligand 1) recognizable peptide DPPA-1 to the sequence of CGKRK, a namely tumor vasculature affinity peptide, to form a new molecule CD peptide. Thereafter, the paclitaxel (PTX)-loaded PCL nanoparticles were developed and modified with the above newly synthesized CD molecules for tumor cells and angiogenesis dual targeting drug delivery. Results of cellular experiments showed that the prepared nanoparticles have a high affinity to both tumor vasculature endothelial cells and tumor cells, which leads to an improved cytotoxicity to cancer cells and inhibition for angiogenesis. In addition, results of in vivo imaging assay exhibited a super tumor targeting efficacy for the CD peptide decorated nanoplatforms. Finally, the pharmacodynamic evaluation was performed and results shown that the tumor-bearing mice treated with CD-NP-PTX achieved the longest medium survival time when compared with others. Simultaneously, different nanoparticles un-loaded with drugs were also subjected to anti-tumor effect studies. Results demonstrated that the mice administrated with D-NP displayed a significantly higher ability of tumor growth inhibition when compared with the NP or C-NP, indicating a super blocking effect of PD-1/PD-L1 pathway for the ^DPPA-1 peptide. Collectively, these results indicated that the fabricated CD-NP-PTX holds great potential in improving the tumor-targeting drug delivery efficacy and anti-glioma effect.