Abstract
3D cultures have gained attention in the field of regenerative medicine for their usefulness as in vitro model of solid tissues. Bottom-up technology to generate artificial tissues or organs is prospective and an attractive approach that will expand as the field of regenerative medicine becomes more translational. We have characterized c-kit positive cardiac stem cells after long-term cultures and established a 3D-nanoculture system using collagen scaffolds. By combining informatics-based studies, including proteomic analyses and microarrays, we sought to generate methods that modeled cardiac regeneration which can ultimately be used to build artificial hearts. Here, we describe the use of biodegradable beads or 3D cultures to study cardiac regeneration. We summarize recent work that demonstrates that, by using a combination of molecular analyses with 3D cultures, it is possible to evaluate concise mechanisms of solid tissue stem cell biology.
Highlights
Heart failure is the leading cause of death in the Western world and is rapidly increasing worldwide [1,2,3], and it occurs due to the dysfunction or loss of cardiomyocytes [4]
Cells grown in 3D cultures proliferate rapidly
When progenitor cells are grown in 3D, stemness can be modulated by manipulating the growth factors they are exposed to and direct differentiation towards a desired linage
Summary
Heart failure is the leading cause of death in the Western world and is rapidly increasing worldwide [1,2,3], and it occurs due to the dysfunction or loss of cardiomyocytes [4]. It was reported that these resident stem cells were capable of contributing to the regeneration of the heart [11] Both iPS cells and tissue resident CSCs are targets for therapy. Among the CSCs we isolated, CSC4A had less sphere-forming ability but higher cardiomyocyte differentiation ability [12, 14] When cocultured, these cells enhanced cardiomyocyte survival in vitro via a paracrine mechanism. To promote resident stem cell function, microbeads embedded with growth factor can be transplanted in the infarcted area. In considering what growth factors induce cardiac stem cells to differentiate, we found that TGF-β enhanced myogenesis and noggin induced beating cardiomyocytes from left atriumderived pluripotent cells (LA-PCs) [20]. We summarize 3D in vitro culture methods and their possible application for the future of regenerative medicine and in vitro models for drug discovery
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