Human iPSC-Vascular smooth muscle cell spheroids demonstrate size-dependent alterations in cellular viability and secretory function.

Human-induced pluripotent stem cells (hiPSC) and their differentiated vascular cells have been revolutionizing the field of regenerative wound healing. These cells are shown to be rejuvenated with immense potentials in secreting paracrine factors. Recently, hiPSC-derived vascular smooth muscle cells (hiPSC-VSMC) have shown regenerative wound healing ability via their paracrine secretion. The quest to modulate the secretory function of these hiPSC-VSMC is an ongoing effort and involves the use of both biochemical and biophysical stimuli. This study explores the development and optimization of a reproducible, inexpensive protocol to form hiPSC-VSMC derived spheroids to investigate the implications of spheroid size on viability and paracrine secretion. Our data show the successful formation of different sizes of spheroids using various amount of hiPSC-VSMC. The hiPSC-VSMC spheroids formed with 10,000 cells strike an ideal balance between overall cell health and maximal paracrine secretion. The conditioned medium from these spheroids was found to be bioactive in enhancing human dermal fibroblast cell proliferation and migration. This research will inform future studies on the optimal spheroid size for regenerative wound healing applications.

Human iPSC-Derived Vascular Smooth Muscle Cells in a Fibronectin Functionalized Collagen Hydrogel Augment Endothelial Cell Morphogenesis.

Tissue-engineered constructs have immense potential as autologous grafts for wound healing. Despite the rapid advancement in fabrication technology, the major limitation is controlling angiogenesis within these constructs to form a vascular network. Here, we aimed to develop a 3D hydrogel that can regulate angiogenesis. We tested the effect of fibronectin and vascular smooth muscle cells derived from human induced pluripotent stem cells (hiPSC-VSMC) on the morphogenesis of endothelial cells. The results demonstrate that fibronectin increases the number of EC networks. However, hiPSC-VSMC in the hydrogel further substantiated the number and size of EC networks by vascular endothelial growth factor and basic fibroblast growth factor secretion. A mechanistic study shows that blocking αvß3 integrin signaling between hiPSC-VSMC and fibronectin impacts the EC network formation via reduced cell viability and proangiogenic growth factor secretion. Collectively, this study set forth initial design criteria in developing an improved pre-vascularized construct.

Pine as fast food: foraging ecology of an endangered cockatoo in a forestry landscape.

Pine plantations near Perth, Western Australia have provided an important food source for endangered Carnaby's Cockatoos (Calyptorhynchus latirostris) since the 1940s. Plans to harvest these plantations without re-planting will remove this food source by 2031 or earlier. To assess the impact of pine removal, we studied the ecological association between Carnaby's Cockatoos and pine using behavioural, nutritional, and phenological data. Pine plantations provided high densities of seed (158,025 seeds ha(-1)) over a large area (c. 15,000 ha). Carnaby's Cockatoos fed throughout these plantations and removed almost the entire annual crop of pine cones. Peak cockatoo abundance coincided with pine seed maturation. Pine seed had energy and protein contents equivalent to native food sources and, critically, is available in summer when breeding pairs have young offspring to feed. This strong and enduring ecological association clearly suggests that removing pine will have a significant impact on this endangered species unless restoration strategies, to establish alternative food sources, are implemented.