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Artificial Cells Containing Stem Cells for Liver Failure.

Stem Cells and Regenerative Medicine.

Towards a Universal Platform for Autologous Stem Cell Gene Therapy: the Induced Pluripotent Stem Cell Breakthrough.

The study of nanomedicine research, to date, has been concentrating on developing nanovectors for medical imaging, drug/gene delivery, and cell targeting, particularly in cancer diagnosis and therapeutics. Although quite successful in some areas, critical challenges remain, especially in the clinical settings. Some of the critical issues include delivery inefficiency, targeting non-specificity, and low uptake of theranostic-payloads by the cancerous lesions upon intravenous injection. Therefore, an alternative approach may be possible, via nanotechnology, by simulating some of the immune cells. In this Technical Note, we propose using specifically designed nanoparticles to simulate neutrophils that are capable of effective cancer cells targeting and killing without the complications in drug loading, biomarker conjugation, and assembly of chemical and physical therapeutic means. The simulated artificial cells mimic neutrophils, namely, granulocytes, according to their biological characteristics, for instance, positively-charged cell surfaces and the ability to release perferin upon binding onto the cancer cells leading to cytolysis. This Technical Note is intended to deliver a new concept in artificially-engineered granulocytes for cancer diagnosis and therapeutics.

Cell-sized lipid vesicles (CLVs) have shown great promise for therapeutic and artificial cell applications, but their fragility and short shelf life has hindered widespread adoption and commercial viability. We present a method to circumvent the storage limitations of CLVs such as giant unilamellar vesicles (GUVs) and single-compartment multisomes (SCMs) by storing them in a double emulsion precursor form. The double emulsions can be stored for at least 8 months and readily converted into either GUVs or SCMs at any time. In this study, we investigate the interfacial parameters responsible for this morphological change, and we also demonstrate the therapeutic potential of CLVs by utilizing them to present a transmembrane protein, neuroligin-2, to pancreatic $\beta$-cells, forming cell-cell synapses that stimulate insulin secretion and cellular growth.

Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (poly-[Hb-SOD-CAT-CA]) contains all three major functions of red blood cells (RBCs) at an enhanced level. It transports oxygen, removes oxygen radicals and transports carbon dioxide. Our previous studies in a 90-minute 30 mm Hg MAP-sustained hemorrhagic shock rat model showed that it was more effective than blood in the lowering of elevated intracellular PCO₂, recovery of ST-elevation and histology of the heart and intestine. This paper analyzes the storage and temperature stability. The allowable storage time for RBCs is about 1 day at room temperature and 42 days at 4°C. Also, RBCs cannot be pasteurized to remove infective agents like HIV and Ebola. PolyHb can be heat sterilized and can be stored for a year even at room temperature. However, poly-[Hb-SOD-CAT-CA] contains both Hb and enzymes, and enzymes are particularly sensitive to storage and heat. We thus carried out studies to analyze its storage stability at different temperatures and heat pasteurization stability. The results of the storage stability show that lyophillization extends the storage time to a year at 4°C and 40 days at room temperature (compared to 42 days and 1 day, respectively, for RBCs). After the freeze-dry process, the enzyme activities of poly-[SFHb-SOD-CAT-CA] was 100 ± 2% for CA, 100 ± 2% for SOD, and 93 ± 3.5% for CAT. After heat pasteurization at 70°C for 2 hours, lyophilized poly-[Hb-SOD-CAT-CA] retained good enzyme activities of CA (97 ± 4%), SOD (100 ± 2.5%) and CAT (63.8 ± 4%). More CAT can be added during the crosslinking process to maintain the same enzyme ratio after heat pasteurization. Heat pasteurization is possible only for the lyophilized form of poly-[Hb-SOD-CAT-CA] and not for the solution. It can be easily reconstituted by dissolving it in suitable solutions that continue to have good storage stability (though less than that for the lyophilized form). According to the P50 value, poly-[SFHb-SOD-CAT-CA] retains its oxygen-carrying ability before and after long-term storage.

In this paper, poly(ethylene glycol)-poly(lactic acid) block-copolymer (PEG-PLA) was prepared and characterized using a Fourier transform infrared spectrophotometer (FTIR). Polyhemoglobin-superoxide dismutase-catalase-carbonic anhydrase (polyHb-SOD-CAT-CA) was formed by crosslinking Hb with SOD, CAT and CA using glutaraldehyde. PEG-PLA encapsulated polyHb-SOD-CAT-CA by oil in water emulsification, forming a PLA-PEG polyHb-SOD-CAT-CA nanocapsule to transport both O₂ and CO₂. It showed a homogeneous particle diameter of about 100 nm, good dispersion and core shell structure, high Entrapment Efficiency (EE%), Drug Loading (DL%) and nanocapsule recovery (%). A lethal hemorrhagic shock model in rats was used to evaluate the therapeutic effect of the PLA-PEG polyHb-SOD-CAT-CA nanocapsule. The results showed that it could effectively decrease CO₂ accumulation and increase mean arterial pressure (MAP) in shock because it acted as both an O₂ carrier and a CO₂ carrier.