Tissue-adhesive wirelessly powered optoelectronic device for metronomic photodynamic cancer therapy.

Metronomic (that is, low-dose and long-term) photodynamic therapy (mPDT) for treating internal lesions requires the stable fixation of optical devices to internal tissue surfaces to enable continuous, local light delivery. Surgical suturing-the standard choice for device fixation-can be unsuitable in the presence of surrounding major nerves and blood vessels, as well as for organs or tissues that are fragile, change their shape or actively move. Here, we show that an implantable and wirelessly powered mPDT device consisting of near-field-communication-based light-emitting-diode chips and bioadhesive and stretchable polydopamine-modified poly(dimethylsiloxane) nanosheets can be stably fixed onto the inner surface of animal tissue. When implanted subcutaneously in mice with intradermally transplanted tumours, the device led to significant antitumour effects by irradiating for 10 d at approximately 1,000-fold lower intensity than conventional PDT approaches. The mPDT device might facilitate treatment strategies for hard-to-detect microtumours and deeply located lesions that are hard to reach with standard phototherapy.

Regulation of human B lymphopoiesis by the transforming growth factor-beta superfamily in a newly established coculture system using human mesenchymal stem cells as a supportive microenvironment.

OBJECTIVES: To characterize and evaluate the validity of a novel coculture system for studying human B-lymphocyte developmental biology. MATERIALS AND METHODS: We developed a long-term culture system to produce B lymphocytes from human CD34(+) cells purified from umbilical cord blood using human mesenchymal stem cells (hMSC) as stroma. We evaluated the effects of several low molecular weight inhibitors, recombinant proteins, and neutralizing antibodies (Abs) as potential regulators of B-lymphocyte development. RESULTS: Our cocultures of 2000 CD34(+) cells in the presence of stem cell factor and Flt3-ligand produced 1-5 x 10(5) CD10(+) cells after 4 weeks of culture. Surface IgM(+) immature B cells began to appear after 4 weeks. We evaluated the negative-regulatory effects of the transforming growth factor (TGF)-beta superfamily on human B lymphopoiesis, and found that adding an anti-activin A antibody enhanced generation of CD10(+) cells two- to three-fold. As well, the proportion of CD10(+) cells in the generated cells increased markedly, indicating that activin A downregulated B lymphopoiesis more efficiently than myelopoiesis. Addition of TGF-beta1 suppressed B-lymphocyte production by 20% to 30%, while addition of an anti-bone morphogenetic protein (BMP)-4 antibody or recombinant BMP-4 had no effect. Therefore, the strength of ability to suppress human B lymphopoiesis seemed to be activin A > TGF-beta1 > BMP-4. None of these three factors influenced the emergence of IgM(+) cells. CONCLUSIONS: hMSC coculture supported human B lymphopoiesis. Activin A selectively suppressed B lymphocyte production.