[Bone mesenchymal stem cell transplantation for acute myocardial infarction: in vivo tracing with multi-modality molecular imaging].

OBJECTIVE: To investigate the feasibility of tracking bone mesenchymal stem cell (BMSCs) dual- labeled with polyethylenimine 2k-superparamagnetic iron oxide (PEI2k-SPIO) and Luciferase transplantation for acute myocardial infarction in vivo by using magnetic resonance imaging (MRI) and fluorescence imaging. METHODS: BMSCs/Luciferase was incubated with culture medium containing PEI2k-SPIO for 24 h. Prussian-blue staining and MTT were used to assess the efficacy and safety of labeling with PEI2k-SPIO. Guided with echocardiography, the dual-labeled BMSCs were injected into the margin of infarction myocardium. MRI and fluorescence imaging were performed to monitor the cells in vivo at different times (1,2,3,7 d). RESULTS: As demonstrated by MTT, there was no significant difference in survival rate between the labeled and unlabeled cells (P>0. 05). Within a week after transplantation, all PEI2k-SPIO-labeled BMSCs showed a significant decreased signal on MRI. Dual-labeled BMSCs were detected bioluminescence with fluorescence imaging, but disappeared after one week. CONCLUSION: Multi- modality imaging can not only trace the location of labeled BMSCs but also demonstrate the survival of labeled BMSCs in vivo.

Multi Stimuli-Responsive Aggregation-Induced Emission Active Polymer Platform Based on Tetraphenylethylene-Appended Maleic Anhydride Terpolymers.

Multi stimuli-responsive aggregation-induced emission (AIE) active polymers have great application prospects in high-tech innovations. Herein, three types of tetraphenylethylene (TPE)-containing monomers were synthesized and utilized in preparing TPE-appended maleic anhydride terpolymers. After hydrolysis, the produced TPE-appended maleic acid terpolymers have identical linear charge densities but different "primary" structures, which created widely varied microenvironments around the carboxylate and TPE groups. Benefiting from the synergistic interaction of the TPE moiety and the terpolymer conformation change, the TPE-appended maleic acid terpolymers exhibited fluorescence changes in response to multi stimuli, including pH, ionic strength, Ca2+, and bovine serum albumin. On both the "signaling" and the "stimuli acceptor" sides, the multi stimuli-responsive fluorescence behavior was influenced markedly by the terpolymer primary structure. The fundamental insights gained in the present work are important for developing an efficient and versatile stimuli-responsive AIE-active polymer platform for chemo-sensing, bioimaging, and so on.

[MR imaging of polyethylenimine-superparamagnetic iron oxide nanoparticle labeled bone marrow mesenchymal stem cells in vitro].

OBJECTIVE: To explore the optimal concentration of polyethylenimine-superparamagnetic iron oxide (PEI2k-SPIO) particles for labeling bone marrow mesenchymal stem cells (BMSCs) in vitro, then to demonstrate the imaging characteristics of the cells by 7.0-T MR scanner. The lowest cell quantity and the optimal cell quantity detected on MR was observed. METHODS: Cells at 2nd passage were inoculated into the 6-hole plate with cover glass. The different concentrations of PEI2k-SPIO (5 microg/mL, 7 microg/mL, 10 microg/mL, 15 microg/mL, 20 microg/mL) were added into different holes, respectively. After labeled with different concentrations of PEI2k-SPIO, the Prussian blue stain was used for determining the labeling efficiency. MTT growth curves were used to identify the activity of BMSCs and to determine the optimal threshold of SPIO nanocomposite particles labeled the stem cells at different PEI2k-SPIO concentrations (7, 10, 15, 20 microg Fe/mL medium). To definite the lowest cells quantity and the optimal observable cells quantity on MR imaging, 1 x 10(6), 1 x 10(5), 1 x 10(4) and 1 x 10(3) cells labeled with optimal threshold of PEI2k-SPIO and 1 x 10(6) cells unlabeled suspended in 0.2 mL agarose (10 g/L), respectively undergone MR scan. RESULTS: MTT growth curves showed the optimal threshold of PEI2k-SPIO labeled BMSCs was 7 microg/mL, which indicates has no adverse effects on the growth of stem cells. At the opimal concentration (7 microg Fe/mL), the lowest observable cell quantity of PEI2k-SPIO-labeled cells for MRI was 1 x 10(4), and the optimal observable cell quantity was 1 x 10(6). CONCLUSION: At the opimal concentration, adverse effect to stem cell activities had not be detected when were labeled with PEI2k-SPIO and the clearly image of MRI of labeled BMSCs could be obtained.

Bcl11b/Ctip2 in Skin, Tooth, and Craniofacial System.

Ctip2/Bcl11b is a zinc finger transcription factor with dual action (repression/activation) that couples epigenetic regulation to gene transcription during the development of various tissues. It is involved in a variety of physiological responses under healthy and pathological conditions. Its role and mechanisms of action are best characterized in the immune and nervous systems. Furthermore, its implication in the development and homeostasis of other various tissues has also been reported. In the present review, we describe its role in skin development, adipogenesis, tooth formation and cranial suture ossification. Experimental data from several studies demonstrate the involvement of Bcl11b in the control of the balance between cell proliferation and differentiation during organ formation and repair, and more specifically in the context of stem cell self-renewal and fate determination. The impact of mutations in the coding sequences of Bcl11b on the development of diseases such as craniosynostosis is also presented. Finally, we discuss genome-wide association studies that suggest a potential influence of single nucleotide polymorphisms found in the 3' regulatory region of Bcl11b on the homeostasis of the cardiovascular system.

Lithium Loaded Octa-Poly(Ethylene Glycol) Based Adhesive Facilitates Axon Regeneration and Reconnection of Transected Peripheral Nerves.

At present, reconnecting the transected nerve in clinic is still mainly reliant on surgery suture. This is a procedure that requires thorough training and is also time consuming. Here, an octa-poly(ethylene glycol) (PEG)-based adhesive for fast reconnecting of the transected peripheral nerve is reported. To enhance the therapeutic efficacy, a succinyl unit is applied to endow the controllably dissolvable property of the adhesive, and lithium is loaded in the adhesive to improve the axonal regeneration. Present data reveal that this adhesive possesses good cytocompatibility and can significantly shorten the reconnecting time of the transected nerve ends compared to that required for suture surgery. Histology, electrophysiological, and behavior assessments indicate that the adhesive reconnected nerves exhibit a low grade of fibrosis, inflammation response, and myoatrophy as well as robust axonal regeneration and functional recovery. Together, these results indicate that this octa-PEG adhesive can act as an alternative to traditional nerve suture in peripheral nerve injury.

Biodegradable 131 Iodine-Labeled Microspheres: Potential Transarterial Radioembolization Biomaterial for Primary Hepatocellular Carcinoma Treatment.

Transarterial radioembolization with radionuclide-labeled microspheres is successfully used in hepatocellular carcinoma (HCC) treatment, but the non-biodegradability and rapid settlement of the microsphere material are associated with unsatisfied distribution and unable for multiple administrations. In this study, a novel biodegradable chitosan-collagen composite microsphere (CCM) with ideal settlement rate is prepared. The Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) results indicate CCMs have desirable shapes with diameters around 10 µm, and considerable biodegradability within 12 weeks. These CCMs are successfully radiolabeled with 131 I and processed efficiency of 70.4 MBq mg-1 of microspheres as well as favorable stability in vitro. Then, 131 I-CCMs are injected into rats with orthotopic HCC via the hepatic artery which effectively improves the median overall survival from 19 to 44 days (p < 0.05). Single photon emission computed tomography (SPECT/CT) imaging and immunohistochemical analysis indicate well-localized biodistribution and consistent stability of 131 I-CCMs in the liver over 28 days. Magnetic resonance imaging (MRI) and gross specimens monitoring confirm the inhibited tumor growth after 131 I-CCMs treatment. In conclusion, these biodegradable 131 I-CCMs exhibit optimal radiolabeling efficiency, stability, and favorably radioembolization effect for orthotopic HCC in a rodent model, suggesting potential for interventional cancer therapy.

Osteogenesis of peripheral blood mesenchymal stem cells in self assembling peptide nanofiber for healing critical size calvarial bony defect.

Peripheral blood mesenchymal stem cells (PBMSCs) may be easily harvested from patients, permitting autologous grafts for bone tissue engineering in the future. However, the PBMSC's capabilities of survival, osteogenesis and production of new bone matrix in the defect area are still unclear. Herein, PBMSCs were seeded into a nanofiber scaffold of self-assembling peptide (SAP) and cultured in osteogenic medium. The results indicated SAP can serve as a promising scaffold for PBMSCs survival and osteogenic differentiation in 3D conditions. Furthermore, the SAP seeded with the induced PBMSCs was splinted by two membranes of poly(lactic)-glycolic acid (PLGA) to fabricate a composited scaffold which was then used to repair a critical-size calvarial bone defect model in rat. Twelve weeks later the defect healing and mineralization were assessed by H&E staining and microcomputerized tomography (micro-CT). The osteogenesis and new bone formation of grafted cells in the scaffold were evaluated by immunohistochemistry. To our knowledge this is the first report with solid evidence demonstrating PBMSCs can survive in the bone defect area and directly contribute to new bone formation. Moreover, the present data also indicated the tissue engineering with PBMSCs/SAP/PLGA scaffold can serve as a novel prospective strategy for healing large size cranial defects.