Each week, In Theory takes on a big idea in the news and explores it from a range of perspectives. This week we’re talking about government compensation for organ donors. Need a primer? Catch up here.
Benjamin D. Humphreys is a nephrologist and chief of the division of nephrology at Washington University in St. Louis. He cares for patients with kidney disease and runs a research laboratory aimed at developing new therapies to treat kidney disease, including stem-cell-based therapies.
Kidney failure is a growing problem in the United States, with more than 100,000 new cases per year. There are not enough kidneys available to transplant all of these patients, so the majority are treated with dialysis. The therapy is certainly life-saving but is also costly, inconvenient for patients and itself causes accelerated heart disease. The risk of death for an average dialysis patient is 20 percent per year.
Dialysis patients make up about one percent of the Medicare population, but paying for dialysis costs seven percent of the entire Medicare budget. Clearly there is a strong need for innovative new therapies and approaches to the problem. We already have some new ideas being developed — at-home and portable dialysis, for example. Yet simply improving the existing technology is an evolutionary change, one that falls well short of what is actually needed: a new kidney that frees patients from devices entirely.
[Other perspectives: The moral case for paying kidney donors]
It is here that the stem-cell revolution of the past 10 years offers a measure of hope. To understand the challenges in growing a kidney from stem cells, it is useful to compare the stem-cell approaches to kidney failure with those for diabetes. Patients with Type 1 diabetes suffer from the failure of a single cell type in the pancreas, called the beta cell. Over the past 10 years, scientists have been successful in generating beta cells in the lab — billions of them — and now the only remaining challenge to cure Type 1 diabetes is find a way to deliver those cells to a patient and keep them alive.
Kidney failure, on the other hand, represents failure of an entire organ comprised of over 30 distinct cell types, all organized in an intricate and complicated pattern. The challenge is not only to grow 30 different cell types, but also how to arrange them in proper orientation. Until two years ago, the prospects for surmounting these challenges appeared slim, despite decades of effort by large teams of scientists around the world.
But recent breakthroughs using human pluripotent stem cells have demonstrated that growing a kidney in a dish may be feasible. Pluripotent stem cells are special in that they possess the ability to differentiate into any cell type in the human body.
By coaxing stem cells to differentiate into two different types, kidney-specific stem cells, then combining them, scientists have discovered that these cells will continue to differentiate on their own, generating a wide variety of cells that are found in a mature kidney. Moreover, the cells pattern themselves into nephrons — the functional unit of the kidney — and these nephrons are structurally quite similar to real nephrons in our own kidney.
This remarkable and surprising advance has, in a short time, changed the way many of us think about the problem of growing an artificial kidney. While still an enormous undertaking, the problem may have a potential solution. Rather than the challenge of generating 30 different cell types, we may only need to develop the two critical kidney stem cells and make sure the conditions in the dish encourage these two cell types to do what they want to do.
A powerful aspect of this human stem-cell approach is that it can be tailored specifically for each patient. Transplant patients generally must take immunosuppressive drugs for the remainder of their lives, to prevent rejection of their kidney by the immune system. This same problem would exist if an artificial kidney were grown in the laboratory using cells from someone other than the patient receiving the kidney.
However, we now have the ability to turn any patient’s cells — from skin or blood on the inside of the mouth, for example — into pluripotent stem cells. One can imagine generating patient-specific stem cells from a patient with kidney failure, using these cells to generate a kidney in a laboratory, and then transplanting that kidney into the same patient. In this scenario, there would be no a need for immunosuppression, and limited ethical concerns.
Of course, a number of very substantial challenges remain. The nephrons that can be grown in the dish currently number only in the hundreds, and a human kidney contains about 400,000 nephrons. Furthermore, the nephrons are not attached to blood vessels, and there is no clear way to insert the kidney into a patient’s blood supply. There is also no way to drain the urine that such a kidney would produce. This will require learning how to grow the drainage system — ureters — that could then be attached to the patient’s bladder.
I was formerly skeptical about the prospects for growing a kidney, but the developments over the past two years have convinced me that this could be a viable option. Realistically, we are still probably 15 to 25 years away from success, so it remains important to pursue other avenues to increase the pool of transplantable kidneys. But certainly our patients have reason for cautious optimism.
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