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Induced pluripotent stem cell

Modeling Hypertrophic Cardiomyopathy in a Dish

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Image of cardiac fibers

Credit: Zhen Ma, University of California, Berkeley

Researchers have learned in recent years how to grow miniature human hearts in a dish. These “organoids” beat like the real thing and have allowed researchers to model many key aspects of how the heart works. What’s been really tough to model in a dish is how stresses on hearts that are genetically abnormal, such as in inherited familial cardiomyopathies, put people at greater risk for cardiac problems.

Enter the lab-grown human cardiac tissue pictured above. This healthy tissue comprised of the heart’s muscle cells, or cardiomyocytes (green, nuclei in red), was derived from induced pluripotent stem (iPS) cells. These cells are derived from adult skin or blood cells that are genetically reprogrammed to have the potential to develop into many different types of cells, including cardiomyocytes.

Stem Cell Science: Taking Aim at Type 1 Diabetes

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human stem cell-derived beta cells

Caption: Insulin-producing pancreatic beta cells (green) derived from human embryonic stem cells that have formed islet-like clusters in a mouse. The red cells are producing another metabolic hormone, glucagon, that regulates blood glucose levels. Blue indicates cell nuclei.
Credit: Photo by B. D. Colen/Harvard Staff; Image courtesy of Doug Melton

For most of the estimated 1 to 3 million Americans living with type 1 diabetes, every day brings multiple fingerpricks to manage their blood glucose levels with replacement insulin [1,2]. The reason is that their own immune systems have somehow engaged in friendly fire on small, but vital, clusters of cells in the pancreas known as the islets—which harbor the so-called “beta cells” that make insulin. So, it’s no surprise that researchers seeking ways to help people with type 1 diabetes have spent decades trying a find a reliable way to replace these islets.

Islet replacement has proven to be an extremely difficult research challenge for a variety of reasons, but exciting opportunities are now on the horizon. Notably, a team of researchers, led by Douglas Melton of Harvard University, Cambridge, MA, and partially funded by NIH, reported groundbreaking success just last week in spurring a human embryonic stem cell (hESC) line and two human-induced pluripotent stem (iPS) cell lines to differentiate into the crucial, insulin-producing beta cells. Not only did cells generated from all three of these lines look like human pancreatic beta cells, they functioned like bona fide, glucose-responsive beta cells in a mouse model of type 1 diabetes [3].

Reprograming Adult Cells to Produce Blood Vessels

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Green mesh with blue dots over a thick red mesh

Caption: New network of blood vessels (green) grown from reprogrammed adult human cells (blue: connective tissue, red: red blood cells)
Credit: Reproduced from R. Samuel et al, Proc Natl Acad Sci U S A. 2013;110:12774-9.

Individuals with heart disease, diabetes, and non-healing ulcers (which can lead to amputation) could all benefit greatly from new blood vessels to replace those that are diseased, damaged, or blocked. But engineering new blood vessels hasn’t yet been possible. Although we’ve learned how to reprogram human skin cells or white blood cells into so-called induced pluripotent stem (iPS) cells—which have the potential to develop into different cell types—we haven’t really had the right recipe to nudge those cells down a path toward blood vessel development.

But now NIH-funded researchers at Massachusetts General Hospital in Boston have taken another step in that direction.