Nephrologists have always been interested in basic biology. At the MDI Biological Laboratory, scientists have been making major scientific contributions to the understanding of the molecular mechanisms of renal tubules and their implications for salt and water balance — and hence their effect on disease — for nearly a century.
In recent years, the focus at the MDI Biological Laboratory has shifted to regenerative biology, including the regeneration of organs. Understanding the complex mechanisms by which an organ is formed is important not only for the understanding of biology, but also for the understanding of the mechanisms involved in repair and regeneration.
Today we know that when our kidneys are damaged by acute injury or chronic disease, they display a specific molecular and cellular response. In patients whose kidneys are damaged by toxic substances or by diabetes mellitus, for example, the body’s first response is to control the injury. Then, almost immediately, repair mechanisms kick in in order to reestablish organ function and diminish damage.
Organ development and repair were major topics at Kidney Week 2016, the annual meeting of the American Society of Nephrology (ASN). Melissa H. Little, Ph.D., and her group from the Kidney Research Laboratory at the Murdoch Childrens Research Institute at The Royal Children’s Hospital in Melbourne, Australia, for instance, discussed how they have induced the cellular building blocks necessary for the development of a new kidney from stem cells in cell culture. The next step is to bring these building blocks together in a structured way.
An increased understanding of kidney formation has allowed scientists like Little to generate so-called “organoids” — complex structures resembling whole organs — in a cell culture. In other words, they can now produce a “kidney in a dish” — the title of Little’s session at Kidney Week. My team is also planning to generate kidneys in a dish in our research at the MDI Biological Laboratory. These organoids can help us to understand how organs are repaired. We can also manipulate them to introduce genetic alterations, which helps us better understand disease processes. These novel approaches may some day allow us to personalize patient treatments. In the future, for instance, it may be possible to develop an organoid that is specific to a particular patient and disease by introducing a personal genetic alteration into a stem cell. This will allow us to better understand the nature of the disease, as well as to screen for new therapies to modulate the cellular response in an individual patient.
Several groups presented ways to make these renal organoids during Kidney Week. Groups from Boston and Australia, as well as from Asia, are now working enthusiastically to develop organoid technology into tools that we can use to enhance the diagnosis and treatment of kidney disease.
In addition, laser-based technology is being used to generate organ-like devices known as “kidneys on a chip.“ An organ-on-a-chip is a microfluidic cell culture device that simulates the activities, mechanics and physiological response of entire organs, making it a more physiologically relevant in vitro model than cells that are cultured in dishes. These microfluidity systems will also be introduced at the MDI Biological Laboratory this year.
Most importantly, the imaging technology for these novel systems has reached new levels of resolution. Electron microscopy and novel microscopy methods are enhancing our ability to visualize what we are doing with kidneys on a chip and other new technologies. Several groups at the MDI Biological Laboratory have been using these modern technologies to analyze various organ species.
The kidney research conducted at the MDI Biological Laboratory has contributed to major advances in the field of nephrology for many decades. This trend is continuing with an increased focus on exciting new stem cell and organoid technologies.
Hermann Haller, M.D. Photo credit: Tom Figiel. Photo credit for image of stained kidney tissue: Tom Deerinck and Mark Ellisman, National Center for Microscopy and Imaging Research
New Organoid Course to Be Offered by the MDI Biological Laboratory
The MDI Biological Laboratory will offer a one-week intensive course from May 27 through June 2, 2018, entitled “Applications of Organoid Technology” in partnership with Hubrecht Organoid Technology (The HUB), a non-profit organization based in the Netherlands. The new “signature” course, which will be held at the laboratory’s Bar Harbor, Maine, campus, is geared to advanced graduate students, post-doctoral trainees and researchers at all levels who want to learn the basics of organoid culture and the most recent developments in the organoid field. The course is one of only a handful in the United States to offer laboratory experience in the emerging field of organoid technology. The course will use cultures from the Living Biobank at The HUB, including organoids from patients with cystic fibrosis and various forms of cancer.