artistic rendering of kidney xray

A non-animal method for predicting kidney toxicity

Scientists at Singapore’s Institute of Bioengineering and Nanotechnology have created a non-animal drug screening method that uses stem cell-derived human kidney cells to predict the toxicity of drugs and other chemicals. The method improves on the reliability and availability of earlier stem cell models, promises to reduce the costs and time it takes to test and develop new drugs, and could eventually eliminate certain animal tests.

iStock_kidney-larger-cropBecause of their role in filtering blood, the kidneys are especially vulnerable to any toxic effects of drugs and other substances that pass through them, but predicting the renal toxicity of such substances has been difficult. As the authors write in their article in Scientific Reports, “Typically, compound nephrotoxicity is only detected during late stages of drug development, which is associated with high costs for the pharmaceutical industry. Animal models have limited predictivity and the development of renal in vitro models with high predictivity has been challenging.”

Using primary human kidney cells in toxicity tests is difficult, as well, due to high variability between donors, and difficulties keeping the cells fully functional during tests. For these reasons, generating a reliable supply of kidney cells from stem cells is preferable. Previous human kidney cell models (including one published by the authors) were produced from human embryonic stems cells (hESCs), which are difficult to access and which raise ethical concerns. This new method instead uses induced pluripotent stem cells (iPSCs) created from more readily available cells, such as human skin cells. iPSCs are genetically “reprogrammed” to an early developmental state, from which they can be coaxed into other kinds of cells. The team’s method produces usable kidney cells within 8 days – much faster than previous stem cell models, as well.

To learn more about using stem cells in toxicity testing, read the “primer” on

alternative toxicity testing non-animal tests stem cells
Organovo's Novogen 3D bioprinter (photo credit: Organovo)

Reading round-up

A few good links to share…

A UCLA scientist is using tiny worms – C. elegans – in a high-throughput, automated format, to screen chemicals for reproductive toxicity.

Patrick-Allard-Lab-0841_mid_credit-UCLA Fielding SPH

Patrick Allard (photo credit: UCLA Fielding School of Public Health)

“With this approach we can now simultaneously screen hundreds of compounds for their toxicity to the reproductive process, which can help to prioritize the chemicals that need further analysis,” Allard said. “Beyond that, once we find compounds that are repro-toxic, we can look further into the stages of reproduction that are affected, and how they are affected.”

Organovo's Novogen 3D bioprinter (photo credit: Organovo)

Organovo’s Novogen 3D bioprinter (photo credit: Organovo)

Chemistry World has a good overview of the growing skin 3D-bioprinting industry, noting that while the initial push is coming from cosmetics companies, “The expertise gained could feed into pharmaceutical research, and even help enable patients’ own cells to be made into almost perfectly compatible skin grafts and eventually replacement organs.”

And in the NIH Director’s Blog, Francis Collins describes NIH-funded efforts to develop neural tissue chips that predict neurotoxicity:

Cultivated neural tissue (photo credit: Michael Schwartz, University of Wisconsin-Madison

Cultivated neural tissue (photo credit: Michael Schwartz, University of Wisconsin-Madison

Each cultured 3D “organoid”—which sits comfortably in the bottom of a pea-sized well on a standard laboratory plate—comes complete with its very own neurons, support cells, blood vessels, and immune cells! As described in Proceedings of the National Academy of Sciences [2], this new tool is poised to predict earlier, faster, and less expensively which new or untested compounds—be they drug candidates or even ingredients in cosmetics and pesticides—might harm the brain, particularly at the earliest stages of development.

Collins also co-authored a Nature commentary summarizing six important lessons learned from Human Genome Project, on its 25th anniversary: embrace partnerships, maximize data-sharing, plan for data analysis, prioritize technology development, address the societal implications of advances, be audacious yet flexible… Read the details here.

3D bioprinting 3D cell & tissue culture alternative toxicity testing organs-on-chips stem cells

Brain-in-a-dish: researchers create “the most complete model of a human brain ever grown in a lab”

Photo courtesy of Ohio State University

Photo courtesy of Ohio State University

Ohio State University researchers Rene Anand and Susan McKay say they have grown a miniaturized human brain from re-programmed adult skin cells. The structure is described in this Washington Post story as “no bigger than a pencil eraser” and is said to contain “all the major structures and 99 percent of the genes present in the brain of a five-week-old fetus.”

“It’s a scalable model that can be engineered to carry the genetic variants that give rise to all these diseases … and it gives us incredible access to things we never have done before,” lead researcher Anand told The Washington Post. “We can screen drugs, we can ask questions, we can follow the development at every stage.”

Because the researchers are patenting their process, they have not released data describing their methods. (They have also formed a commercial startup.) But according to an OSU press release, the team has already used the technique to model autism, Alzheimer’s, and Parkinson’s disease “in-a-dish,” and hopes to receive funding from the Small Business Technology Transfer program to use the model in drug development.

The announcement comes on the heels of another advance in organotypic brain modeling – a 3D bioprinted structure developed by Rodrigo Lozano and colleagues at the University of Wollongong in Australia. A functional brain “organoid” that can be subjected to environmental manipulations, or genetically engineered to reproduce inherited conditions, holds great promise for human-relevant toxicity testing, more efficient drug-candidate screening, and the study of neurodevelopmental and neurodegenerative diseases.

3D bioprinting 3D cell & tissue culture disease-in-a-dish drug discovery stem cells
Rod photoreceptors (in green) within a "mini retina" derived from human iPS cells in the lab.

3D “mini retina” from stem cells

Scientists at Johns Hopkins University School of Medicine have cultivated functional 3-dimensional human retinal tissue in vitro from induced human pluripotent stem cells.  And in a significant technical advance over previous cultured retina studies, the resulting tissue exhibits mature cell differentiation and organization, and is able to detect light.

From the JHU press release:

(Lead investigator M. Valeria Canto-Soler) says that the newly developed system gives them the ability to generate hundreds of mini-retinas at a time directly from a person affected by a particular retinal disease such as retinitis pigmentosa. This provides a unique biological system to study the cause of retinal diseases directly in human tissue, instead of relying on animal models.

The system, she says, also opens an array of possibilities for personalized medicine such as testing drugs to treat these diseases in a patient-specific way. In the long term, the potential is also there to replace diseased or dead retinal tissue with lab-grown material to restore vision.

The study appears in last week’s issue of Nature Communications.

(To learn more about stem cells – especially about their potential in toxicity testing – see this stem cell “primer” on

stem cells toxicity testing alternatives