3 research outputs found
Long-Term Engraftment of Human Cardiomyocytes Combined with Biodegradable Microparticles Induces Heart Repair
Cardiomyocytes derived from human induced pluripotent stem
cells (hiPSC-CMs) are a promising cell source for cardiac repair
after myocardial infarction (MI) because they offer several
advantages such as potential to remuscularize infarcted tissue,
integration in the host myocardium, and paracrine therapeutic
effects. However, cell delivery issues have limited their potential application in clinical practice, showing poor survival and
engraftment after transplantation. In this work, we hypothesized that the combination of hiPSC-CMs with microparticles
(MPs) could enhance long-term cell survival and retention in the
heart and consequently improve cardiac repair. CMs were
obtained by differentiation of hiPSCs by small-molecule manipulation of the Wnt pathway and adhered to biomimetic
poly(lactic-co-glycolic acid) MPs covered with collagen and
poly(D-lysine). The potential of the system to support cell
survival was analyzed in vitro, demonstrating a 1.70-fold and
1.99-fold increase in cell survival after 1 and 4 days, respectively. The efficacy of the system was tested in a mouse MI
model. Interestingly, 2 months after administration, transplanted
hiPSC-CMs could be detected in the peri-infarct area. These cells
not only maintained the cardiac phenotype but also showed
in vivo maturation and signs of electrical coupling. Importantly,
cardiac function was significantly improved, which could be
attributed to a paracrine effect of cells. These findings suggest
that MPs represent an excellent platform for cell delivery in the
field of cardiac repair, which could also be translated into an
enhancement of the potential of cell-based therapies in other
medical applications
Revealing cell populations catching the early stages of human embryo development in naive pluripotent stem cell cultures
Naive human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryo's epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naive human induced PSC (hiPSC) cultures. It is noteworthy that these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represent the main cell population, interestingly we detect a cell population with gene and transposable element expression profile closely resembling the totipotent eight-cell (8C)-stage human embryo, and three cell populations analogous to trophectoderm cells at different stages of their maturation process: transition, early, and mature stages. Moreover, we reveal the presence of cells resembling primitive endoderm. Thus, 5iLAF naive hiPSC cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period
An engineered periosteum for efficient delivery of rhBMP-2 and mesenchymal progenitor cells during bone regeneration
During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 mu g/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses