One-step 3D Differentiation of Cardiac Cells from Adult Human iPS Cells
- Detailed Technology Description
- Current state-of-the-art human iPS cell differentiation into contracting cardiomyocytes (CMs)follows either a 2D sheet approach or employs 3D cell aggregates (embryoid bodies). Both ofthese techniques require cells to be dissociated for downstream applications, including formationof engineered heart tissues and potential clinical applications, resulting in multiple cell handlingsteps and high levels of cell death. This method cultures and differentiates human iPS cells intocardiomyocytes directly in PEG-fibrinogen, a biodegradable hybrid biomaterial. 2D culturing ordifferentiating prior to 3D hydrogel formation is not required. Cardiomyocytes generated by thismethod retain their contractile function at ~140 beats/minute for several months and haveobservable aligned sarcomeres, Z-bands, H-bands, and t-tubules. Sarcomeric α-actinin, Cx43,and Nkx2.5 have been detected throughout the entire tissue (Panels c & d below). This methodcan be used for more rapid, cost effective production of 3D cardiomyocyte structures for drugscreening, engineered cardiac tissue formation, or other uses.
- *Abstract
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Engineered cardiac tissues can be useful in medical applications, drug screens, and research. Inthe U.S. alone, the regenerative cardiac tissue market is expected to top $20 billion by 2019.Generating cardiac tissue from induced pluripotent stem cells (iPS cells) provides the ability tostudy human cardiac physiology and drug responses in culture, and the potential to createcardiac cells for clinical therapies. These cardiac tissues also avoid ethical concerns involving theuse of embryonic stem cells. However, tools and reagents for working with these cells areexpensive and culturing can be time-consuming. A faster method for growing and differentiatinghuman iPS cells directly in a 3D environment has been devised that saves both time and moneywhile generating high quality, mature cardiac tissue.
Advantages include:
(1) Faster and less expensive than existing methods
(2) Differentiates directly in 3D, reducing cell handling and increasing cell survival by up to 2X
(3) Allows formation of mature cardiac structures not observed using other approaches
(4) 3D geometries are flexible and compatible as printable hydrogels
(5) Human iPSCs can be used — no embryonic stem cells are needed
- Country/Region
- USA
