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.
Latest mini-organ, a prostate, fingers BPA. A team at the University of Illinois, at Chicago, has added the prostate gland to the growing list of “organoids” that have been grown from stem cells in the lab. The tiny gland that produces semen in men has an unusually high rate of cancer compared to other organs. Prior research has linked that cancerous nature to exposure to the hormone estrogen during fetal growth, including synthetic estrogen mimics like the chemical BPA (bisphenol A) found in many plastics.
Unlike the other organs associated with male gender, which form very early in fetal development, the prostate develops later when stem cells’ roles are more narrowly defined to creating specific tissues. The team, led by Gail Prins, had previously shown that prostate stem cells grown in the presence of BPA formed cells more likely to show signs of cancer. But that did not allow them to determine what really triggered the increase in cancer. So, they decided to grow mini prostates and look at all the cells as they developed in the organoid.
“What we were doing originally with the human prostate stem cells is we were mixing and growing them in vivo,” Prins told Medical Daily. “The idea to generate this organoid came from the first author, Esther Calderon-Gierszal; she was my graduate student. ‘They’ve done it for other organs,’ she thought. ‘Let’s try it for a prostate.’”
The researchers pushed embryonic stem cells to grow into the several different tissues found in a prostate gland using a cocktail of hormones. Although much smaller than a normal prostate the cells did self-organize into structures that resembled the gland. When they grew the organoid in the presence of BPA they found an unusually large number of prostate specific stem cells. So, it appears just the increased number of stem cells increases the likelihood a few will go bad and form cancer.
A round up of all the mini-organs. The journal Nature has written a very accessible wrap up in its news section on all the various organs that have been simulated in a lab dish since a Japanese team reported the phenomenon for the first time in 2008. After a fun lead-in explaining the science, Cassandra Willyard runs through what has been accomplished so far in the stomach, kidney, and liver.
Part of a miniature stomach grown in the lab, stained to reveal various cells found in normal human stomachs [Credit: Kyle McCracken]
The fun in the opening section comes from the fact that given the right environment, stem cells are pretty darn good at self-organizing into the multiple tissue types that become a specific organ. So much so, that the early teams that saw it in the lab were shocked and did not at first know what they had.
Willyard starts with quotes from Madeline Lancaster, a post-doctoral fellow in a lab at the Institute for Molecular Biotechnology in Vienna, Austria. She found milky looking spheres in the lab cultures and when she cut into them she found multiple types of nerves. So she grabbed her mentor and reported:
“I’ve got something amazing. You’ve got to see it.”
She also discusses the work that led Hans Clevers, a researcher at Hubrecht Institute in Utrecht, the Netherlands, to report the creation of mini-guts in 20009. They grew the cells in a gel that resembled the structure that naturally surrounds cells. In this “at-home” environment stem cells formed much more complex tissue than he had hoped.
“The structures, to our total astonishment, looked like real guts,” Clevers said. “They were beautiful.”
The author also lets Clevers talk about taking his work the next step, using the gut organoids to screen for drugs for related diseases. If you have been following this work, Willyard’s piece is a must read.
Second clinical trial site for diabetes. Opening multiple clinical trial sites accelerates the process of determining whether a new therapy is safe and effective. So we were thrilled to get the announcement from ViaCyte that they would begin enrolling patients at a second location for the diabetes trial we helped them launch by funding the first clinical trial site at the University of California, San Diego.
That trial uses pancreatic cells grown from embryonic stem cells that are protected from immune attack by a semi-permeable pouch. The second site, at the University of Alberta Hospitals in Edmonton, Canada, is being funded in part by Alberta Innovates as well as by the JDRF Canadian Clinical Trials Network. JDRF also helps support the San Diego trial through its US office.
The lead researcher for the Alberta trial, James Shapiro, developed the procedure for transplanting pancreatic tissue from cadavers that became known as “the Edmonton Protocol.” That protocol has changed many lives, but because it requires life-long immunosuppression, doctors only recommend it for the most severe diabetics. The small number of donor pancreases also limits its use. Shapiro commented about the value and need for something like the ViaCyte therapy in a company press release picked up by Yahoo Finance, and dozens of other sites:
“The fact remains that new treatments are sorely needed, not only for the high risk patients but for all patients suffering from this life-altering disease. The remarkable promise of the (ViaCyte) product candidate is that a virtually limitless source of appropriate human cells can be transplanted without the need for lifetime immunosuppression.”