Defining Lineage-Specific Membrane Fluidity Signatures that Regulate Adhesion Kinetics.

Cellular membrane fluidity is a critical modulator of cell adhesion and migration, prompting us to define the systematic landscape of lineage-specific cellular fluidity throughout differentiation. Here, we have unveiled membrane fluidity landscapes in various lineages ranging from human pluripotency to differentiated progeny: (1) membrane rigidification precedes the exit from pluripotency, (2) membrane composition modulates activin signaling transmission, and (3) signatures are relatively germ layer specific presumably due to unique lipid compositions. By modulating variable lineage-specific fluidity, we developed a label-free "adhesion sorting (AdSort)" method with simple cultural manipulation, effectively eliminating pluripotent stem cells and purifying target population as a result of the over 1,150 of screened conditions combining compounds and matrices.

Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling.

Timely controlled oxygen (O) delivery is crucial for the developing liver. However, the influence of O on intercellular communication during hepatogenesis is unclear. Using a human induced pluripotent stem cell-derived liver bud (hiPSC-LB) model, we found hypoxia induced with an O-permeable plate promoted hepatic differentiation accompanied by TGFB1 and TGFB3 suppression.

Negative Pressure Wound Dressing Reduces Surgical Site Infections in Infants after Closed Abdominal Procedures: A Preliminary Report.

Introduction:  Negative pressure wound therapy (NPWT) is a novel tool to reduce surgical site infections (SSIs). Although SSIs are a common source of morbidity in infants undergoing laparotomy, the cost of the available NPWT devices has restricted its use to adult high-risk patients. We developed a low-cost method of NPWT in infants and analyzed its impact on the incidence of SSIs in infant patients.

Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells.

Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive "reverse" screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme.

Comparison of calcimimetic R568 and calcitriol in mineral homeostasis in the Hyp mouse, a murine homolog of X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) caused by mutations in the Phex gene is the most common human inherited phosphate wasting disorder characterized by enhanced synthesis of fibroblast growth factor 23 (FGF23) in bone, renal phosphate wasting, 1,25(OH)D (1,25D) deficiency, rickets and osteomalacia. Here we studied the effects of calcimimetic R568 and calcitriol treatment in the Hyp mouse, a murine homolog of XLH. We hypothesized that mineral homeostasis is differentially affected by R568 and 1,25D with respect to the PTH-vitamin D-FGF23-Klotho axis and bone health.

Multilineage communication regulates human liver bud development from pluripotency.

Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture.

Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation.

Transplantation of in-vitro-generated organ buds is a promising approach toward regenerating functional and vascularized organs. Though it has been recently shown in the context of liver models, demonstrating the applicability of this approach to other systems by delineating the molecular mechanisms guiding organ bud formation is critical. Here, we demonstrate a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells (MSCs).

Transient vascularization of transplanted human adult-derived progenitors promotes self-organizing cartilage.

Millions of patients worldwide are affected by craniofacial deformations caused by congenital defects or trauma. Current surgical interventions have limited therapeutic outcomes; therefore, methods that would allow cartilage restoration are of great interest. A number of studies on embryonic limb development have shown that chondrogenesis is initiated by cellular condensation, during which mesenchymal progenitors aggregate and form 3D structures.

Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant.

Generation of functional and vascularized organs from human induced pluripotent stem cells (iPSCs) will facilitate our understanding of human developmental biology and disease modeling, hopefully offering a drug-screening platform and providing novel therapies against end-stage organ failure. Here we describe a protocol for the in vitro generation of a 3D liver bud from human iPSC cultures and the monitoring of further hepatic maturation after transplantation at various ectopic sites. iPSC-derived specified hepatic cells are dissociated and suspended with endothelial cells and mesenchymal stem cells.