Applications of human pluripotent stem cells (hPSCs) for disease modelling or cell therapy are hindered by low efficiency and heterogeneity of target cell types differentiated from hPSCs, such as motor neurons (MNs). Here the authors develop a method to derive highly pure motor neuron progenitor populations from human embryonic and induced pluripotent stem cells that yield functional MNs.

/pdf/generation-and-expansion-of-highly-pure-motor-neuron-3zg8y1mqps.pdf

Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells

Synthetic polypeptides from the ring-opening polymerization of N-carboxyanhydrides (NCAs) are one of the most important biomaterials. The unique features of these synthetic polypeptides, including their chemical diversity of side chains and their ability to form secondary structures, enable their broad applications in the field of gene delivery, drug delivery, bio-imaging, tissue engineering, and antimicrobials. In this review article, we summarize the recent advances in the design of polypeptide-based supramolecular structures, including complexes with nucleic acids, micelles, vesicles, hybrid nanoparticles, and hydrogels. We also highlight the progress in the chemical design of functional polypeptides, which plays a crucial role to manipulate their assembly behaviours and optimize their biomedical performances. Finally, we conclude the review by discussing the future opportunities in this field, including further studies on the secondary structures and cost-effective synthesis of polypeptide materials.

Synthetic polypeptides: from polymer design to supramolecular assembly and biomedical application

Directing the differentiation of induced pluripotent stem cells into motor neurons has allowed investigators to develop new models of amyotrophic lateral sclerosis (ALS). However, techniques vary between laboratories and the cells do not appear to mature into fully functional adult motor neurons. Here we discuss common developmental principles of both lower and upper motor neuron development that have led to specific derivation techniques. We then suggest how these motor neurons may be matured further either through direct expression or administration of specific factors or coculture approaches with other tissues. Ultimately, through a greater understanding of motor neuron biology, it will be possible to establish more reliable models of ALS. These in turn will have a greater chance of validating new drugs that may be effective for the disease.

/pdf/modeling-als-with-motor-neurons-derived-from-human-induced-33rpyy7zs3.pdf

Modeling ALS with motor neurons derived from human induced pluripotent stem cells.

Recent advances in amino acid N-carboxyanhydrides and synthetic polypeptides: chemistry, self-assembly and biological applications

Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons

Efficient derivation of large-scale motor neurons (MNs) from human pluripotent stem cells is central to the understanding of MN development, modelling of MN disorders in vitro and development of cell-replacement therapies. Here we develop a method for rapid (20 days) and highly efficient (~70%) differentiation of mature and functional MNs from human pluripotent stem cells by tightly modulating neural patterning temporally at a previously undefined primitive neural progenitor stage. This method also allows high-yield (>250%) MN production in chemically defined adherent cultures. Furthermore, we show that Islet-1 is essential for formation of mature and functional human MNs, but, unlike its mouse counterpart, does not regulate cell survival or suppress the V2a interneuron fate. Together, our discoveries improve the strategy for MN derivation, advance our understanding of human neural specification and MN development, and provide invaluable tools for human developmental studies, drug discovery and regenerative medicine.

/pdf/high-efficiency-motor-neuron-differentiation-from-human-3biwnzcrpo.pdf

High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1

Intervention of the inflammation cascade with tumor necrosis factor-α (TNF-α) monoclonal antibodies or receptors represents a major approach in clinical immunotherapy against inflammatory diseases, which however, often suffers from high cost, autoimmunity to antibodies, and various side effects.[1] siRNA-mediated RNA interference (RNAi) has recently emerged as a potent modality in regulating gene expression by suppressing mRNA translation;[2-13] its high efficiency and specificity has made it a promising treatment paradigm for TNF-α-mediated inflammatory disorders.[14-18] The therapeutic potential of siRNA was recently exemplified by a report of attenuating systemic inflammation by targeting orally delivered Map4k4 siRNA to gut-associated macrophages (GAMs).[19] Owing to the infiltration of GAMs to systemic reticuloendothelial tissues, Map4k4 siRNA-mediated TNF-α knockdown in GAMs extended to other tissues and thus induced systemic anti-inflammatory effects.[19]

/pdf/supramolecular-self-assembled-nanoparticles-mediate-oral-3pxkaulfjo.pdf

Supramolecular Self‐Assembled Nanoparticles Mediate Oral Delivery of Therapeutic TNF‐α siRNA against Systemic Inflammation

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High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1

Supramolecular Self‐Assembled Nanoparticles Mediate Oral Delivery of Therapeutic TNF‐α siRNA against Systemic Inflammation