Citations

Regenerative medicine offers a curative approach to treating heart disease through multiple emerging therapeutic concepts. Decellularized organ scaffolds are being optimized to guide and spatially organize stem cell differentiation in efforts to rebuild functional tissues. Additionally, pluripotent stem cells offer a transformative cell source to differentiate into the full spectrum of cellular building blocks. Adult cardiac tissues have been used as extracellular scaffolds as a proof of principle; however, matching the developmental stages of embryonic scaffold with primitive cardiac progenitors may be used to optimize the differentiation and maturation of bioengineered cardiac tissues. Our novel approach uses embryo-derived decellularized hearts as scaffolds to promote embryonic stem cell differentiation. Further, we determined that agitation with 0.25% sodium dodecyl sulfate (SDS) solution was the most effective protocol to maintain matrix integrity while eliminating endogenous cells. The scaffolds were successfully reseeded with different cellular sources derived from pluripotent stem cells to achieve beating cardiac tissues characterized by endothelial, cardiac, and smooth muscle markers. Therefore, embedding stem cells within a tissue-specific environment matched to the developmental stage of the progenitors may offer a practical solution for stem-cell-derived applications such as disease modeling, pharmaceutical safety testing, and screening of novel therapeutic targets.

AbstractThe liver differs from other organs in that two vascular systems deliver its blood – the hepatic artery and the portal vein. However, how the two systems interact is not fully understood. We therefore studied the microvascular geometry of rat liver hepatic artery and portal vein injected with the contrast polymer Microfil®. Intact isolated rat livers were imaged by micro‐CT and anatomic evidence for hepatic arteriolo‐portal venular shunts occurring between hepatic artery and portal vein branches was found. Simulations were performed to rule out the possibility of the observed shunts being artifacts resulting from image blurring. In addition, in the case of specimens where only the portal vein was injected, only the portal vein was opacified, whereas in hepatic artery injections, both the hepatic artery and portal vein were opacified. We conclude that mixing of the hepatic artery and portal vein blood can occur proximal to the sinusoidal level, and that the hepatic arteriolo‐portal venular shunts may function as a one‐way valve‐like mechanism, allowing flow only from the hepatic artery to the portal vein (and not the other way around).