By coating tiny gel beads with lung-derived stem cells and then allowing them to self-assemble into the shapes of the air sacs found in human lungs, researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have succeeded in creating three-dimensional lung “organoids.” The laboratory-grown lung-like tissue can be used to study diseases including idiopathic pulmonary fibrosis, which has traditionally been difficult to study using conventional methods.
“While we haven’t built a fully functional lung, we’ve been able to take lung cells and place them in the correct geometrical spacing and pattern to mimic a human lung,” said Dr. Brigitte Gomperts, an associate professor of pediatric hematology/oncology and the study’s lead author.
Idiopathic pulmonary fibrosis is a chronic lung disease characterized by scarring of the lungs. The scarring makes the lungs thick and stiff, which over time results in progressively worsening shortness of breath and lack of oxygen to the brain and vital organs. After diagnosis, most people with the disease live about three to five years. Though researchers do not know what causes idiopathic pulmonary fibrosis in all cases, for a small percentage of people it runs in their families. Additionally, cigarette smoking and exposure to certain types of dust can increase the risk of developing the disease.
To study the effect of genetic mutations or drugs on lung cells, researchers have previously relied on two-dimensional cultures of the cells. But when they take cells from people with idiopathic pulmonary fibrosis and grow them on these flat cultures, the cells appear healthy. “Scientists have really not been able to model lung scarring in a dish,” said Gomperts, who is a member of the UCLA Broad Stem Cell Research Center. The inability to model idiopathic pulmonary fibrosis in the laboratory makes it difficult to study the biology of the disease and design possible treatments.
Gomperts and her colleagues started with stem cells created using cells from adult lungs. They used those cells to coat sticky hydrogel beads, and then they partitioned these beads into small wells, each only 7 millimeters across. Inside each well, the lung cells grew around the beads, which linked them and formed an evenly distributed three-dimensional pattern. To show that these tiny organoids mimicked the structure of actual lungs, the researchers compared the lab-grown tissues with real sections of human lung.
“The technique is very simple,” said Dan Wilkinson, a graduate student in the department of materials science and engineering and the paper’s first author. “We can make thousands of reproducible pieces of tissue that resemble lung and contain patient-specific cells.”
Moreover, when Wilkinson and Gomperts added certain molecular factors to the 3-D cultures, the lungs developed scars similar to those seen in the lungs of people who have idiopathic pulmonary fibrosis, something that could not be accomplished using two-dimensional cultures of these cells.
Using the new lung organoids, researchers will be able to study the biological underpinnings of lung diseases including idiopathic pulmonary fibrosis, and also test possible treatments for the diseases. To study an individual’s disease, or what drugs might work best in their case, clinicians could collect cells from the person, turn them into stem cells, coax those stem cells to differentiate into lung cells, then use those cells in 3-D cultures. Because it’s so easy to create many tiny organoids at once, researchers could screen the effect of many drugs. “This is the basis for precision medicine and personalized treatments,” Gomperts said.
Technique uses 3-D weaving to grow a living hip replacement
With a goal of treating worn, arthritic hips without extensive surgery to replace them, scientists have programmed stem cells to grow new cartilage on a 3-D template shaped like the ball of a hip joint. What’s more, using gene therapy, they have activated the new cartilage to release anti-inflammatory molecules to fend off a return of arthritis.
The technique, demonstrated in a collaborative effort between Washington University School of Medicine in St. Louis and Cytex Therapeutics Inc. in Durham, N.C., is described July 18 in Proceedings of the National Academy of Sciences.
The discovery one day may provide an alternative to hip-replacement surgery, particularly in younger patients. Doctors are reluctant to perform such operations in patients under age 50 because prosthetic joints typically last for less than 20 years. A second joint-replacement surgery to remove a worn prosthetic can destroy bone and put patients at risk for infection.
“Replacing a failed prosthetic joint is a difficult surgery,” said Farshid Guilak, PhD, a professor of orthopedic surgery at Washington University. “We’ve developed a way to resurface an arthritic joint using a patient’s own stem cells to grow new cartilage, combined with gene therapy to release anti-inflammatory molecules to keep arthritis at bay. Our hope is to prevent, or at least delay, a standard metal and plastic prosthetic joint replacement.”
Scientists at the Gladstone Institutes have invented a new way to create three-dimensional human heart tissue from stem cells. The tissue can be used to model disease and test drugs, and it opens the door for a precision medicine approach to treating heart disease. Although there are existing techniques to make three-dimensional tissues from heart cells, the new method dramatically reduces the number of cells needed, making it an easier, cheaper, and more efficient system.
“We have bioengineered micro-scale heart tissues with a method that can easily be reproduced, which will enable scientists in stem cell biology and the drug industry to study heart cells in their proper context,” said first author Nathaniel Huebsch, PhD, a postdoctoral fellow in the Conklin lab at Gladstone. “In turn, this will enhance our ability to discover treatments for heart disease.”
Creating heart cells from induced pluripotent stem cells (iPSCs) that are derived from a patient’s skin cells enables scientists to study and test drugs on that patient’s specific disease. However, cells made from iPSCs are relatively immature, resembling heart cells in an embryo more than cells in an adult. As such, these cells are inadequate for drug testing because they do not properly predict how a drug will affect adult heart cells. Additionally, heart cells created from iPSCs are challenging to make and work with, so creating large quantities can be difficult. Therefore, the fewer cells needed, the better.
The micro heart muscle addresses both of these concerns.
Effectiveness of Gene Editing in Human Stem Cells Improves Tenfold Using New Technique
For the first time, researchers have employed a gene-editing technique involving low-dose irradiation to edit the genome of patient stem cells, according to a study published in the journal Stem Cells Translational Medicine. This method, developed by researchers in the Cedars-Sinai Board of Governors Regenerative Medicine Institute, is 10 times more effective than techniques currently in use.
“This novel technique allows for far more efficient gene editing of stem cells and will increase the speed of new discoveries in the field,” said co-senior author Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute.
The irradiation method could prove effective in learning more about diseases such as spinal muscular atrophy, muscular dystrophy and Huntington’s disease. Gene editing allows scientists to correct disease causing mutations and, theoretically, cure the disease in the petri dish. Additionally, gene-editing technology allows scientists to create disease mutations in normal cells, thus modeling human disease.