5 research outputs found
Additional file 4: Figure S3. of Enhanced in vitro osteogenic differentiation of human fetal MSCs attached to 3D microcarriers versus harvested from 2D monolayers
Kinetics of osteogenic gene expression during osteogenic differentiation of S27 hfMSC in PCL-TCP scaffold cultures. (A) Cultures seeded with 2D monolayer-harvested (2D MNL-harv) and microcarrier-harvested (3D MC-harv) cells, (B) Cultures seeded with microcarrier-harvested (2D MNL-harv) and microcarrier-bound (3D MC-bound) cells. Two-way repeated measures ANOVA with post-hoc Tukey correction was performed between 3D MC-harv, 2D MNL-harv and 3D MC-bound cells using Graphpad, (*p < 0.05 and at least a 2-fold difference in the means). Of the multiple comparisons performed, data representing a single comparison is shown: (A) 3D MC-harv vs 2D MNL-harv, (B) 3D MC-bound vs 2D MNL-harv. (TIFF 544 kb
Additional file 5: Table S1. of Enhanced in vitro osteogenic differentiation of human fetal MSCs attached to 3D microcarriers versus harvested from 2D monolayers
List of Taqman Gene Expression Assay IDs for genes investigated by qPCR in this study. (DOCX 13 kb
Additional file 2: of Impact of adopting the 2013 World Health Organization criteria for diagnosis of gestational diabetes in a multi-ethnic Asian cohort: a prospective study
Table S2. Linear regression models of the associations between reclassification of gestational diabetes mellitus diagnosis and birth weight-for-GA, with the inclusion of women without diabetes in pregnancy. (DOCX 12 kb
Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease
Delivery of mRNA-based therapeutics to the perinatal
brain holds
great potential in treating congenital brain diseases. However, nonviral
delivery platforms that facilitate nucleic acid delivery in this environment
have yet to be rigorously studied. Here, we screen a diverse library
of ionizable lipid nanoparticles (LNPs) via intracerebroventricular
(ICV) injection in both fetal and neonatal mice and identify an LNP
formulation with greater functional mRNA delivery in the perinatal
brain than an FDA-approved industry standard LNP. Following in vitro optimization of the top-performing LNP (C3 LNP)
for codelivery of an adenine base editing platform, we improve the
biochemical phenotype of a lysosomal storage disease in the neonatal
mouse brain, exhibit proof-of-principle mRNA brain transfection in vivo in a fetal nonhuman primate model, and demonstrate
the translational potential of C3 LNPs ex vivo in
human patient-derived brain tissues. These LNPs may provide a clinically
translatable platform for in utero and postnatal
mRNA therapies including gene editing in the brain