118 research outputs found
STEM CELL AND HYPOXIA-BASED APPROACHES TO ENGINEERING BLOOD VESSELS
No full textThe success of tissue regenerative therapies is contingent upon functional and multicellular vasculature within the redeveloping tissue. Endothelial cells (ECs), which comprise the vasculature’s inner lining, are intrinsically able to form nascent networks; however, without recruitment of pericytes, supporting cells that surround microvessel endothelium, these endothelial-only structures regress. To reconstruct a typical in vivo microvascular architecture, distinct cell sources of ECs and pericytes have traditionally been used within naturally occurring extracellular matrices (ECMs). However, the limited clinically-relevant human cell sources and inherent chemical and physical properties of natural materials hamper the translational potential of these approaches. Human pluripotent stem cells (hPSCs) are an unlimited source of progenitors from which vascular cells may be derived. Controlled and robust differentiation of hPSCs toward vascular lineages is critical for the advancement and future of patient-specific vascular therapeutics.
In this work, we first derived a bicellular vascular population of ECs and pericytes, termed early vascular cells (EVCs), from hPSCs that undergoes vascular morphogenesis in a synthetic matrix to form networks that integrate with host vasculature. Next, we found that low oxygen environments enhance endothelial lineage commitment in EVCs. Subsequently, we compared arterial and venous ECs to an adult stem cell population, endothelial colony forming cells (ECFCs), revealing that ECFCs deposited abundant ECM; mature ECs only produced these ECM proteins under hypoxic conditions via hypoxia-inducible factors 1α and 2α. Finally, we found that EVCs differentiated under low oxygen conditions could produce copious amounts of collagen IV and fibronectin as well as angiogenic growth factors. EVCs differentiated under atmospheric conditions did not demonstrate such abundant ECM expression.
Collectively, these findings reveal that control over microenvironmental cues via appropriate signaling molecules is able to robustly produce critical cells of the vasculature, which may in turn serve as novel therapies for vascular diseases or be incorporated into engineered tissue
Multiple, Interconvertible States of Human Pluripotent Stem Cells
No full textThree recent studies, including Buecker et al. (2010), in this issue of Cell Stem Cell, report that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can exist in distinct but interconvertible states and describe a robust expansion of human ESCs/iPSCs that resemble mouse ESCs
Potential of human induced pluripotent stem cells derived from blood and other postnatal cell types
No full text Human induced pluripotent stem (iPS) cells have been generated from various cell types including blood cells, and offer certain advantages as a starting population for reprogramming postnatal somatic cells. Unlike adult stem cells, iPS cells can proliferate limitlessly in culture while retaining their potential to differentiate into any cell type, including hematopoietic lineages. Derivation of patient-specific iPS cells, in combination with improved hematopoietic differentiation protocols, provides an alternative to generate histocompatible stem cells for bone marrow transplantation. In addition, the ability to reprogram blood cells and redifferentiate iPS cells back to hematopoietic lineages provides opportunities to establish novel models for acquired and inherited blood diseases. This article will summarize recent progress in human iPS cells derived from blood cells and hematopoietic differentiation from iPS cells. Advantages of blood as a source for reprogramming and applications in regenerative medicine will be discussed. </jats:p
And Then There Were None: No Need for Pluripotency Factors to Induce Reprogramming
No full textWhile most factors used as reprogramming transgenes can be replaced by other means, Oct4 has remained essential until now. Three recent papers have now broken this barrier through the use of opposing lineage specifying transgenes and chemical modulation, thus signifying a milestone in advancing our understanding of pluripotency induction
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