1. Enhanced adhesion and proliferation of bone marrow mesenchymal stem cells on β‑tricalcium phosphate modified by an affinity peptide
Guozong Wang, Zhentao Man, Hua Xin, Yi Li, Changshun Wu, Shui Sun Mol Med Rep. 2019 Jan;19(1):375-381. doi: 10.3892/mmr.2018.9655. Epub 2018 Nov 13.
Mesenchymal stem cells (MSCs) are often used in orthopedic tissue engineering, and bone marrow‑derived mesenchymal stem cells (BMSCs) are currently considered the gold standard. One of the most important issues in MSC‑based tissue engineering therapy is the low number of MSCs in pathological tissues. Achieving efficient recruitment of MSCs to defective or damaged tissues in vivo has been a difficult hurdle. The aim of the present study was to construct a biomaterial that can effectively recruit BMSCs to facilitate the repair of pathological tissues. So functional β‑tricalcium phosphate (β‑TCP) was synthesized using the BMSC affinity peptide DPIYALSWSGMA (DPI) adsorbed onto β‑TCP through an adsorption/freeze‑drying strategy. C57BL/6 mouse‑derived BMSCs were seeded onto the DPI peptide‑modified β‑TCP (β‑TCP‑DPI); in vitro experiments demonstrated that β‑TCP‑DPI enhanced BMSC adhesion and proliferation compared with unmodified β‑TCP. Results from the present study indicated that functional β‑TCP may be used as an ideal scaffold in tissue engineering and in regenerative medicine.
2. Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells
Tao Zhang, Xiao-Hang Li, Dian-Bao Zhang, Xiao-Yu Liu, Feng Zhao, Xue-Wen Lin, Rui Wang, Hong-Xin Lang, Xi-Ning Pang Mol Ther Nucleic Acids. 2017 Sep 15;8:220-231. doi: 10.1016/j.omtn.2017.06.016. Epub 2017 Jun 23.
Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs) can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs), which can be used as a therapeutic approach against type 1 diabetes (T1D). As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2) promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI). Functionally, bmMSCs were reprogrammed into IPCs via COUP-TFI suppression and MafA overexpression. The differentiated cells expressed higher levels of genes specific for islet endocrine cells, and they released C-peptide and insulin in response to glucose stimulation. Transplantation of IPCs into streptozotocin-induced diabetic mice caused a reduction in hyperglycemia. Mechanistically, COUP-TFI bound to the DR1 (direct repeats with 1 spacer) element in the Ins2 promoter, thereby negatively regulating promoter activity. Taken together, the data provide a novel mechanism by which COUP-TFI acts as a negative regulator in the Ins2 promoter. The differentiation of bmMSCs into IPCs could be improved by knockdown of COUP-TFI, which may provide a novel stem cell-based therapy for T1D.
3. Human bone marrow mesenchymal stem cells-derived microRNA-205-containing exosomes impede the progression of prostate cancer through suppression of RHPN2
Shuangjian Jiang, Chengqiang Mo, Shengjie Guo, Jintao Zhuang, Bin Huang, Xiaopeng Mao J Exp Clin Cancer Res. 2019 Dec 17;38(1):495. doi: 10.1186/s13046-019-1488-1.
Background: Human bone marrow mesenchymal stem cells (hBMSCs) are implicated in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the physiological mechanisms by which exosomal miR-205 derived from hBMSCs may modulate the growth of prostate cancer cells. Methods: Microarray-based gene expression profiling of prostate cancer was adopted to identify differentially expressed genes and regulatory miRNAs, which identified the candidates RHPN2 and miR-205 as the study focus. Then the binding affinity between miR-205 and RHPN2 was identified using in silico analysis and luciferase activity detection. Prostate cancer cells were co-cultured with exosomes derived from hBMSCs treated with either miR-205 mimic or miR-205 inhibitor. Subsequently, prostate cancer cell proliferation, invasion, migration, and apoptosis were detected in vitro. The effects of hBMSCs-miR-205 on tumor growth were investigated in vivo. Results: miR-205 was downregulated, while RHPN2 was upregulated in prostate cancer cells. RHPN2 was a target of miR-205, and upregulated miR-205 inhibited prostate cancer cell proliferation, invasion, and migration and promoted apoptosis by targeting RHPN2. Next, experiments demonstrated that hBMSCs-derived exosomes carrying miR-205 contributed to repressed prostate cancer cell proliferation, invasion, and migration and enhanced apoptosis. Furthermore, in vivo assays confirmed the inhibitory effects of hBMSCs-derived exosomal miR-205 on prostate cancer. Conclusion: The hBMSCs-derived exosomal miR-205 retards prostate cancer progression by inhibiting RHPN2, suggesting that miR-205 may present a predictor and potential therapeutic target for prostate cancer.
