Physiological normoxia and absence of EGF is required for the long-term propagation of anterior neural precursors from human pluripotent cells

Widespread use of human pluripotent stem cells (hPSCs) to study neuronal physiology and function is hindered by the ongoing need for specialist expertise in converting hPSCs to neural precursor cells (NPCs). Here, we describe a new methodology to generate cryo-preservable hPSC-derived NPCs that retain an anterior identity and are propagatable long-term prior to terminal differentiation, thus abrogating regular de novo neuralization. Key to achieving passagable NPCs without loss of identity is the combination of both absence of EGF and propagation in physiological levels (3%) of O2. NPCs generated in this way display a stable long-term anterior forebrain identity and importantly retain developmental competence to patterning signals. Moreover, compared to NPCs maintained at ambient O2 (21%), they exhibit enhanced uniformity and speed of functional maturation, yielding both deep and upper layer cortical excitatory neurons. These neurons display multiple attributes including the capability to form functional synapses and undergo activity-dependent gene regulation. The platform described achieves long-term maintenance of anterior neural precursors that can give rise to forebrain neurones in abundance, enabling standardised functional studies of neural stem cell maintenance, lineage choice and neuronal functional maturation for neurodevelopmental research and disease-modelling

The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity

Salma M Mohyeldin, Mohammed M Mehanna, Nazik A Elgindy Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Purpose: This article investigated the influence of novel rifampicin nanosuspension (RIF NS) for enhancing drug delivery properties. Methods: RIF NS was fabricated using the antisolvent precipitation technique. The impact of solvent type and flow rate, stabilizer type and concentration, and stirring time and apparatus together with the solvent–antisolvent volume ratio on its controlled nanocrystallization has been evaluated. NSs were characterized by transmission electron microscopy, particle size and zeta potential analysis, solubility, and dissolution profiles. The compatibility between RIF and the stabilizer was investigated via Fourier transform infrared spectroscopy and the differential scanning calorimetry techniques. The shelf-life stability of the RIF NS was assessed within a period of 3 months at different storage temperatures. Cell cytotoxicity was evaluated using 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on lung epithelial cells. Results: Polyvinyl alcohol at 0.4% w/v, 1:15 methanol to deionized water volume ratio and 30-minutes sonication were the optimal parameters for RIF NS preparation. Nanocrystals were obtained with a nanometeric particle size (101 nm) and a negative zeta potential (-26 mV). NS exhibited a 50-fold enhancement in RIF solubility and 97% of RIF was dissolved after 10 minutes. The RIF NS was stable at 4±0.5°C with no significant change in particle size or zeta potential. The MTT cytotoxicity assay of RIF NS demonstrated a good safety profile and reduction in cell cytotoxicity with half maximal inhibitory concentration values of 0.5 and 0.8 mg/mL for free RIF and RIF NS, respectively. Conclusion: A novel RIF NS could be followed as an approach for enhancing RIF physicochemical characteristics with a prominence of a safer and better drug delivery. Keywords: controlled nanocrystallization, cytotoxicity, nanosuspension, polyvinyl alcohol, rifampici

Precisely Fabricated Sulpiride-Loaded Nanolipospheres with Ameliorated Oral Bioavailability and Antidepressant Activity [Corrigendum]

Mohyeldin SM, Samy WM, Ragab D, Abdelmonsif DA, Aly RG, Elgindy NA. Int J Nanomed. 2021;16:2013–2044 The authors have advised that Figure 10A on page 2041 is incorrect owing to an inadvertent error during the preparation of representative images for Figure 10. The corrected version of Figure 10 is shown below. Figure 10 Photomicrograph of representative tissues within normal histologic limits of the brain (A,F and K), intestinal mucosa (B,G and L), gastric mucosa (C,H and M), kidney (D,I and N) and liver (E,J and O) in the negative control, blank, and SUL-LPS, respectively, ×200, H&E.Abbreviations: H&E, hematoxylin and eosin; SUL-LPS, sulpiride-loaded lipospheres. The authors sincerely apologize for this error and affirm that it does not affect the data interpretation and the conclusion of the study

Modeling the behavior of human induced pluripotent stem cells seeded on melt electrospun scaffolds

Abstract Background Human induced pluripotent stem cells (hiPSCs) can form any tissue found in the body, making them attractive for regenerative medicine applications. Seeding hiPSC aggregates into biomaterial scaffolds can control their differentiation into specific tissue types. Here we develop and analyze a mathematical model of hiPSC aggregate behavior when seeded on melt electrospun scaffolds with defined topography. Results We used ordinary differential equations to model the different cellular populations (stem, progenitor, differentiated) present in our scaffolds based on experimental results and published literature. Our model successfully captures qualitative features of the cellular dynamics observed experimentally. We determined the optimal parameter sets to maximize specific cellular populations experimentally, showing that a physiologic oxygen level (∼ 5%) increases the number of neural progenitors and differentiated neurons compared to atmospheric oxygen levels (∼ 21%) and a scaffold porosity of ∼ 63% maximizes aggregate size. Conclusions Our mathematical model determined the key factors controlling hiPSC behavior on melt electrospun scaffolds, enabling optimization of experimental parameters

DNA damage response in adult stem cells: pathways and consequences.

In contrast to postmitotic or short-lived somatic cells, tissue-specific stem cells must persist and function throughout life to ensure tissue homeostasis and repair. The enormous functional demands and longevity of stem cells raises the possibility that stem cells might be uniquely equipped to maintain genomic integrity in ways different than somatic cells. Indeed, evidence suggests that stem cell compartments possess unique properties that combine to either limit or, in some instances, accelerate DNA damage accrual.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: re.jinfo:eu-repo/semantics/publishe