Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.
Hearts with nerve. When trying to heal a damaged heart you can’t just worry about the heart muscle, you also need to pay attention to the nerves that tell the muscle what to do. A team at John Hopkins has grown nerves from stem cells in the lab that connect to heart cells growing in the same dish, a key step to making the two tissues collaborate where you need them.
Specifically, the team grew sympathetic nerves—a name that never made much sense to me, but basically refers to all those nerves that function without us thinking about their role, like breathing and heartbeat. Faulty sympathetic nerves lead to several diseases including high blood pressure. While it will likely be many years before this work leads to lab-grown heart muscle and nerves teaming up in actual patients, using nerves grown from stem cells made from patients, teams can begin studying those diseases in the lab now.
The researchers published their work in Cell Stem Cell, and ScienceDaily posted the university’s press release. Much of the work involved what has become classic in stem cell research, trying many different combinations of growth factors applied at different moments in time until they arrived at just the right recipe to end up with sympathetic nerves.
Inner ear grown in a dish. Researchers at Children’s Hospital, Boston, and Indiana University have succeeded in growing a sac-like tissue that contains the inner ear organs responsible for balance. Starting with mouse embryonic stem cells, the resulting one millimeter structure contained functioning sensory hair cells critical to hearing.
Jeffrey Holt of Children’s said, in the hospital’s Vector blog, that he hopes to use the lab model of the inner ear to test potential therapies for balance disorders he sees in children coming to the facility. The lab-grown tissues seem to behave like the real thing, responding to mechanical stimuli by producing tiny electrical currents. The team published its research in Nature Communications.
Getting adult stem cells to stay stem cells. While pluripotent stem cells like embryonic stem cells can generally be grown in the lab indefinitely, most stem cells from adult tissue eventually mature into specific adult tissue and loose the stem cell property of being able to renew themselves. Researchers at Harvard and Massachusetts General Hospital (MGH) developed a process that keeps adult stem cells from maturing into specific tissue. This could eventually help teams scaling up production of potential therapies but can already speed up and reduce the cost of much of the research getting to that point.
The MGH team worked with airway stem cells, which have been particularly hard to maintain in the lab and require constant collection of new cells that can require invasive procedures such as bronchoscopy. This has made diseases such as asthma and COPD hard to study using stem cell models of disease, which are generally more accurate than animal models.
They started by looking at what internal cellular signaling pathways were active in cells that were maturing into specific tissue but that were not active in the stem cells. They found two such pathways and developed ways to shut down those cell signals. That in turn kept cell in the stem cell state and allowed them to be grown in large quantities in the lab. They were even able to do this with the few airway stem cells that patients cough up when collecting a sputum sample. This would greatly simplify stem cell collection for researchers and patients.
“We also found that the same methodology works for many tissues of the body — from the skin to the esophagus to mammary glands. Many of these organ tissues cannot currently be cultured, so it remains to be seen whether scientists in these areas will be able to grow stem cells from samples acquired from other minimally invasive procedures, including the collection of secretions. If all this becomes possible, it would represent a big step forward for personalized medical approaches to disease,” said Jayaraj Rajagopal, senior author on the paper published in Cell Stem Cell in an MGH press release posted by ScienceDaily
Tunable pituitary tissue. While prior research has reported creating tiny pituitary organoids in a dish, those tissues were not very precise in what hormones they produce. Given the fact that the pituitary gland secretes hormones for growth, reproduction and the stress response, and patients with pituitary disease have varying deficiencies in specific hormones, random production of various hormones isn’t likely to be effective treatment.
Now a team at the Sloan Kettering Institute for Cancer Research led by Lorenz Studer has developed a system of adjusting two factors used to drive stem cells to become pituitary tissue. This system results in adjustable proportions of the tissue that produces different hormones. That way you can get more or less of the various hormones that a patient may need.
When transplanted into rats, the lab grown tissue succeeded in secreting multiple hormones and causing appropriate responses in the animals. Bastian Zimmer, the first author on the paper in Stem Cell Reports, suggested the technique could be used to generate specific cell types for patients with different types of hypopituitarism.
“For the broad application of stem cell-derived pituitary cells in the future, cell replacement therapy may need to be customized to the specific needs of a given patient population,” Zimmer said in a release provided by the journal and posted by MedicalXpress.