A miniature dialysis-culture device allows high-density human-induced pluripotent stem cells expansion from growth factor accumulation

Three-dimensional aggregate-suspension culture is a potential biomanufacturing method to produce a large number of human induced pluripotent stem cells (hiPSCs); however, the use of expensive growth factors and method-induced mechanical stress potentially result in inefficient production costs and difficulties in preserving pluripotency, respectively. Here, we developed a simple, miniaturized, dual-compartment dialysis-culture device based on a conventional membrane-culture insert with deep well plates. The device improved cell expansion up to approximately ~3.2 to 4×107 cells/mL. The high-density expansion was supported by reduction of excessive shear stress and agglomeration mediated by the addition of the functional polymer FP003. The results revealed accumulation of several growth factors, including fibroblast growth factor 2 and insulin, along with endogenous Nodal, which acts as a substitute for depleted transforming growth factor-β1 in maintaining pluripotency. Because we used the same growth-factor formulation per volume in the upper culture compartment, the cost reduced in inverse proportional manner with the cell density. We showed that growth-factor-accumulation dynamics in a low-shear-stress environment successfully improved hiPSC proliferation, pluripotency, and differentiation potential. This miniaturised dialysis-culture system demonstrated the feasibility of cost-effective mass production of hiPSCs in high-density culture.

A Panel Study of Factor Accumulation and Export Quality

Cross-sectional data show Global North countries export higher quality products at a point in time. Product-level panel data can address if countries improve their export quality over time. The literature has addressed this practically relevant panel question only in small samples over the short term. We addressed it for a large sample, over the long run, focusing on the hitherto overlooked endogeneity between export quality and factor accumulation and the role of export composition. We utilized a two-tiered panel: the panel of countries and the panel of products each country trades. We found some evidence that middle-income countries often upgrade export quality within the same product, but that high- and low-income countries do this less often. Our results appear to support product cycle theory: some countries climb the value ladder, others are competed off from the ladder’s top, and new countries enter markets. Technology appears to be a potential basis for consolidating trade competitiveness over time, as skill accumulation becomes more widespread across countries and loses significance as an explanatory variable. Our results provide some explanation of why Global North countries might resist sharing technology. This research is timely with deadlocked multilateral trade negotiations and looming trade wars. It attempts to contribute to an evidence-based guide to trade policy.

High-density hiPSCs expansion supported by growth factors accumulation in a simple dialysis-culture platform

Three-dimensional aggregate-suspension culture can produce large numbers of human induced pluripotent stem cells (hiPSCs); however, use of expensive growth factors and method-induced mechanical stress potentially result in inefficient production costs and difficulties in preserving pluripotency. Here, we developed a simple, miniaturized, dual-compartment dialysis-culture device based on a conventional membrane-culture insert with deep well plates. The device allowed growth-factor accumulation and improved cell expansion up to ~ 32 × 106 cells/mL, and reduction of excessive shear stress and agglomeration following addition of the functional polymer FP003 supported high-density expansion. The results revealed accumulation of several growth factors, including fibroblast growth factor 2 and insulin, along with endogenous NODAL, which acts as a substitute for depleted transforming growth factor-β1 in maintaining pluripotency. Because we used the same growth-factor formulation per volume in the upper culture compartment, cost reduction increased significantly in proportional manner with cell density. We showed that growth-factor-accumulation dynamics in a low-shear-stress environment successfully improved hiPSC proliferation, pluripotency, and differentiation potential. This miniaturised dialysis-culture system demonstrated the feasibility and cost-effective mass production of hiPSCs in high-density culture.