Adverse events related to unapproved stem cell products and other regenerative interventions: recommendations for more robust regulation of the direct-to-consumer marketplace

Tweetable abstract Adverse events continue to occur in the direct-to-consumer market for unapproved regenerative interventions and US FDA alone cannot adequately address the problem. Other public health strategies are needed to provide better patient protection.

Tissue and cell interactions in mammalian PGC development

ABSTRACT Primordial germ cells (PGCs) form early in embryo development and are crucial precursors to functioning gamete cells. Considerable research has focussed on identifying the transcriptional characteristics and signalling pathway requirements that confer PGC specification and development, enabling the derivation of PGC-like cells (PGCLCs) in vitro using specific signalling cocktails. However, full maturation to germ cells still relies on co-culture with supporting cell types, implicating an additional requirement for cellular- and tissue-level regulation. Here, we discuss the experimental evidence that highlights the nature of intercellular interactions between PGCs and neighbouring cell populations during mouse PGC development. We posit that the role that tissue interactions play on PGCs is not limited solely to signalling-based induction but extends to coordination of development by robust regulation of the proportions and position of the cells and tissues within the embryo, which is crucial for functional germ cell maturation. Such tissue co-development provides a dynamic, contextual niche for PGC development. We argue that there is evidence for a clear role for inter-tissue dependence of mouse PGCs, with potential implications for generating mammalian PGCLCs in vitro.

Relationship of Matrix Stiffness and Cell Morphology in Regulation of Osteo Genesis and Adipogenesis of BMSCs

Backgrounds: Both matrix stiffness and cell morphology have been found as important factors directing MSCs (mesenchymal stem cells) differentiation, but cells also spontaneously adapt their morphology under matrix stiffness stimulation. This study aimed to investigate the interplay of cell morphology and matrix stiffness on osteogenesis and adipogenesis of rBMSCs(rat bone BMSCs) on 2D substrates. Methods and Results: First, we modulated MSCs morphology through different fibronectin (FN) concentrations on tissue culture plates (TCPs). We found FN promoted and osteogenesis of BMSCs while suppressing adipogenesis, mediated by FN-induced F-actin polymerization and cell spreading. Based on these findings, we modulated BMSCs morphology on 0.5 kPa and 32 kPa CytoSoft® plates through FN concentrations. We found BMSCs on 0.5 kPa substrates coated with 300μg/ml of FN manifested similarly spreading morphology with cells on 32 kPa substrates coated with 100 μg/ml of FN, and cells in both groups dominantly commit osteogenesis. On the other hand, BMSCs on 32 kPa substrates coated with 30μg/ml of FN manifested similarly restricted morphology with cells in on 0.5 kPa substrates with 100μg/ml of FN, and in both groups cells mainly commit adipogenesis. Immunofluorescence staining indicated YAP/TAZ mainly located in cytoplasm when cells exhibited restricted morphology on stiff matrices, while exhibiting significant nuclear translocation when cells spread on soft matrices. Conclusions: Cell morphology overrode effects of matrix stiffness on BMSCs differentiation through more robust regulation of YAP/TAZ. Matrix stiffness depended on cell morphology to regulate osteogenesis and adipogenesis of BMSCs.

Legal and institutional frameworks for capital market regulation in Nigeria: recasting the agendas beyond compliance-based regulation

Purpose The purpose of the paper is to explore the legal and institutional frameworks for optimal regulation of capital market beyond compliance-based regulation, to enable the market to deliver on its strategic role as the enabler of efficient allocation of resources and economic growth. Design/methodology/approach The paper relies on doctrinal approach to assess the existing regulatory approaches and prospects for the future. Findings The paper found that the regulatory authorities unduly concentrate on compliance-based and sanction-based regimes without sufficient emphasis on innovations and transformative solutions that foster diversification and efficiency in the market. The paper also found that the deployment of innovations and transformative solutions complemented with robust regulation is positively correlated with capital market growth. Originality/value The paper offers fresh insights on the optimal approaches to regulation of capital market that transcend compliance-based and sanction-based regimes to reliance on innovative tools that expand, diversify and effectuate the functionality and utility of capital market.

Making the investment case for national regulatory authorities

Well-functioning national regulatory authorities (NRAs) ensure access to safe, effective, quality-assured, and affordable medical products. However, the benefits of their work are often unseen and difficult to attribute, thereby making NRAs undervalued and under-resourced, particularly in low- and middle-income countries. This paper offers three key arguments NRAs and other stakeholders can use to advocate for greater investment in regulatory systems strengthening—medical products regulation effectively safeguards public health; effective regulation improves health system’s efficiency by increasing access to affordable medical products, contributing to universal health coverage; and robust regulation strengthens local pharmaceutical manufacturing and bolsters pharmaceutical trade. NRAs’ critical role in health systems is indisputable, yet they need to better promote their value to receive the requisite resources to function effectively.

Critical role of lipid membranes in polarization and migration of cells: a biophysical view

Cell migration plays vital roles in many biologically relevant processes such as tissue morphogenesis and cancer metastasis, and it has fascinated biophysicists over the past several decades. However, despite an increasing number of studies highlighting the orchestration of proteins involved in different signaling pathways, the functional roles of lipid membranes have been essentially overlooked. Lipid membranes are generally considered to be a functionless two-dimensional matrix of proteins, although many proteins regulating cell migration gain functions only after they are recruited to the membrane surface and self-organize their functional domains. In this review, we summarize how the logistical recruitment and release of proteins to and from lipid membranes coordinates complex spatiotemporal molecular processes. As predicted from the classical framework of the Smoluchowski equation of diffusion, lipid/protein membranes serve as a 2D reaction hub that contributes to the effective and robust regulation of polarization and migration of cells involving several competing pathways.