Adult Stem Cells Programmed Into Embryonic State
A pluripotent stem cell. Researchers have programmed adult stem cells back into the embryonic state.
Cambridge University Department of Engineering
When physicians run out of treatment options they look to a nascent field known as bioengineering. Specialized scientists apply engineering principles to biological systems, opening up the possibility of creating new human tissue, organs, blood and even corneas such as the one shown here. Waiting lists for organ transplants continue to be lengthy so the race to save lives with bioengineered body parts is on. Here’s a look at some of the most notable achievements in recent years.
Fraunhofer Institute for Interfacial Engineering and Biotechnology
Producing small amounts of artificial skin to graft on patients and use for toxicity testing has been possible for years. Human skin cells are cultivated in the lab and then embedded in a collagen scaffold. In 2011, the Fraunhofer Institute for Interfacial Engineering and Biotechnology introduced a system that can rapidly manufacture two-layer artificial skin models. Their Tissue Factory has the capacity to make 5,000 skin sheets in a month.
Princeton University / Frank Wojciechowski
Reproducing 3-D biological structures, particularly the complex human ear, presents significant challenges for bioengineers. A team at Princeton University led by mechanical and aerospace engineering associate professor Michael McAlpine used 3-D printing technology to make a functional ear from calf cells and electronic materials. The ear that debuted in May 2013 is no mere replacement -- it can pick up radio frequencies well beyond the range that human ears normally detect.
Popular Science via Getty Images
Surgeon Anthony Atala directs the Wake Forest Institute for Regenerative Medicine and is known for growing new human cells, tissues and organs -- particularly ones that advance urology. Atala and his team’s bioengineered bladders succeeded in clinical trials. The bladders were constructed from patients’ cells that were grown over two months on a biodegradable scaffold and then implanted. Patients included children with spina bifida who risked kidney failure. It’s been several years since then and the results are positive. “These constructs appear to be doing well as patients get older and grow,” Atala told the NIH Record.
Massachusetts General Hospital/PNAS
Being able to make blood vessels in the lab from a patient’s own cells could mean better treatments for cardiovascular disease, kidney disease and diabetes. In 2011, the head of California-based Cytograft Tissue Engineering reported progress in a study where three end-stage kidney disease patients were implanted with blood vessels bioengineered in the lab. After eight months the grafts continued to work well, easing access to dialysis. Then this month a team at Massachusetts General Hospital found a way to encourage stem-like cells to develop into vascular precursor cells, a key step on the way to becoming blood vessel cells. They generated long-lasting blood vessels in living mice.
Ott Lab / Massachusetts General Hospital
Artificial heart devices have been surgically implanted since the 1980s, but no device has been able to replace the human heart as effectively as a healthy biological one. After all, a human heart pumps 35 million times in a single year. Recently scientists have made advances in adding more biological material to artificial heart devices. In May the French company Carmat prepared to test an artificial device containing cow heart tissue. At Massachusetts General Hospital, surgeon Harald C. Ott and his team are working on a bioartificial heart scaffold while MIT researchers recently printed functional heart tissue from rodent cells.
Wake Forest University Baptist Medical Center
Bioengineers are working on it, but the liver is one of the largest, most challenging organs to recreate. In 2010 bioengineers at Wake Forest University Baptist Medical Center grew miniature livers in the lab using decellularized animal livers for the structure and human cells. This month, a team from the Yokohama City University Graduate School of Medicine published results of a study where they reprogrammed human adult skin cells, added other cell types, and got them to grow into early-stage liver “buds.” Currently the scientists can produce about 100 of them, but the study’s lead author Takanori Takebe told the Wall Street Journal that even a partial liver would require tens of thousands.
Harvard Apparatus Regenerative Technology
In April, after an international team of surgeons spent nine hours operating on her at Children's Hospital of Illinois in Peoria, 32-month old Hannah Warren became the youngest patient to ever receive a bioengineered organ. Scientists had made a windpipe for her using her own bone marrow cells. Born without a trachea, she needed help breathing, eating, drinking and talking. Harvard Bioscience created the custom scaffold and bioreactor for the experimental procedure. Sadly Hannah died on July 7 due to complications from a more recent surgery on her esophagus. Despite the high risks, bioengineers say they will continue to move ahead.
When a ruptured or degenerating disc causes chronic back pain, treatment is limited. At worst, patients undergo surgery to fuse vertebrae together and then have limited flexibility. Over the past several years artificial discs have emerged as an alternative, but they can wear out as they work. In 2011, a research team from Cornell University bioengineered implants using gel and collagen seeded with rat cells that were then successfully placed into rat spines. This summer Duke bioengineers took things further, coming up with a gel mixture they think can help regenerate tissue when injected into the space between discs.
Little by little, bioengineered intestines are being grown in the lab to diagnose digestive disorders and to help patients born without a piece of intestine. In 2011, Cornell biological and environmental engineering assistant professor John March began collaborating with Pittsburgh-based pediatric surgeon David Hackam on a small artificial intestine using collagen and stem cells. Then last year in Switzerland, EPFL professor Martin Gijs led a project in the Laboratory of Microsystems to create a miniature intestinal wall from cultured epithelial cells and electronics called NutriChip to identify foods that cause inflammation. Scientists at Harvard’s Wyss Institute also made a “gut-on-a chip” to mimic the real thing using intestinal cells in a tiny silicon polymer device.
University of California, San Francisco
One in 10 American adults will have some level of chronic kidney disease, according to the Centers for Disease Control and Prevention. Currently around 600,000 patients in the U.S. have chronic kidney failure. Most rely on dialysis while a fraction of them actually get transplants. Scientists from the University of California, San Francisco are on a mission to create a sophisticated artificial kidney device made with human kidney cells, silicon nanofilters and powered by blood pressure. The project, led by UCSF nephrologist William Fissell and bioengineering professor Shuvo Roy, aims to begin testing the kidney device in 2017.
Scientists in Spain said on Wednesday they had made mature cells in living mice revert to their youthful, versatile state, in a step toward the goal of tissue regeneration by stem cells.
Right now, the technique is at its earliest stage and is hedged with safety questions, which makes it impossible to envisage in humans.
But, said the researchers, it opens up a new strategy leading to a beguiling end: that one day damaged tissue will be healed by simply reprogramming nearby adult cells into replacements for the lost or diseased area. A transplant would not be needed.
Stem cells have excited huge interest in medical research.
They are immature cells that differentiate into the specialized cells that comprise and maintain the human body.
In 2006, a team led by Shinya Yamanaka in Japan announced a breakthrough.
A clutch of four genes introduced into adult cells in a lab dish rewound these cells back to their baby state.
These so-called induced pluripotent stem cells -- known by their acronym of iPS -- have since become the most closely-followed innovation in the field.
Despite many hurdles, they are seen by some as being even more promising than embryonic stem cells, the "gold standard" for versatility but a source hotly opposed by moral conservatives.
Reporting in the journal Nature, a team led by Manuel Serrano and Maria Abad of the Spanish National Cancer Research Center created genetically-modified mice that carried the four "Yamanaka genes."
The genes were then switched on by administering a drug in the mice's water.
Cells in the rodents' kidney, stomach, intestine and pancreas all showed signs of being reprogrammed, back to an extremely versatile or "totipotent" state that seemed more like embryonic stem cells than lab-dish iPS, the team reported.
The technique confirms that reprogramming can be done in living tissue, and not just in the lab dish, said Serrano.
"We can now start to think about methods for inducing regeneration locally and in a transitory manner for a particular damaged area," he said.
Other researchers were divided as to whether the work ws a game-changer and all cautioned that daunting obstacles lay ahead.
There was no evidence about what happened to the cells in the mice after they had been reprogrammed.
In addition, the animals developed clusters of tumors called teratomas, although this had been quite expected as part of the research. Creating teratomas is a benchmark of the versatility of an experimental stem cell.
"This paper is very exciting. Clearly, nobody wishes to do this for therapeutic purposes because this leads to the formation of tumors," Ilaria Bellantuono, a University of Sheffield researcher, told the Science Media Center, a not-for-profit organization in London.
"However, this is a proof of concept that pluripotency can be achieved in vivo," or in living animals.
The process "still needs these iPS cells to be safely converted to useful 'adult' cells in the body," warned Chris Mason, a professor of regenerative medicine at University College London.
"The major challenge will be tightly controlling every step in this potential approach in order to deliver clinical benefits whilst avoiding significant complications."