Systematic under-funding and a shortage of kidney donors has left hundreds of thousands of American kidney patients languishing on transplant waiting lists and undergoing regular dialysis while their treatment options remain limited. Those patients fortunate enough to receive a transplant will almost always require anti-rejection drugs for the rest of their lives (although there have been exceptions where trial patients have also received stem cells from the donor).
Nevertheless, ongoing studies into regenerative medicine and kidney disease have generated much excitement. Research has been ongoing in many areas of kidney stem cells focusing on kidney-specific stem cells, more easily obtainable mesenchymal stem cells (MSCs) and laboratory-manipulated iPSCs (induced pluripotent stem cells). There has even been progress towards the eventual construction of a fully-functioning artificial kidney using stem cells and nanotechnology.
Kidney Disease in the US
The fully functional human kidney is an elegant and complex marvel of biological evolution. Its functional unit is the nephron, a structure responsible for filtering the blood, returning essential electrolytes to the body and excreting the rest as urine. The kidney is also responsible for the creation of numerous hormones including erythropoietin (EPO), responsible for increasing red blood cell production in the bone marrow; calcitriol (vitamin D3), important in calcium and phosphate absorption and renin, an enzyme involved in blood pressure regulation.
There are many ways in which the kidneys can be damaged or put under strain but the most common culprit is Type II diabetes which lies behind around half of the 20,000 instances of chronic kidney disease (CKD) in the US – that is a lot of people. CKD is diagnosed when kidney function is reduced to 30% or less of the normal, for a period of three months, which is generally regarded as 120ml/min, remembering that a quarter of the five liters (5,000ml) of cardiac output a minute go to the kidneys. Elevated blood glucose levels place a constant strain on the kidneys and, over time, damages the filtration apparatus and, when compensatory mechanisms break down, steadily reduce kidney function. Symptoms of CKD can be mild and generic (headaches, fatigue, high blood pressure, sallow complexion, anemia, itching, swelling, shortness of breath, etc.) which may impede diagnosis.
For those who survive long enough, CKD will eventually progress to kidney failure (end stage renal disease). At this stage, the kidney is reduced to 10% or less (15ml/min or less) of normal function and the patient will be put on dialysis, an intensive and expensive treatment whereby the dialysis machine takes the place of the patient’s kidneys. Dialysis costs around $80,000 a year per patient for a total annual burden of nearly $50 billion. The waiting list for a donor kidney currently numbers around 100,000 with patients usually waiting between three and five years for a transplant. This in itself costs around $200,000, not counting the ongoing anti-rejection regime that follows.
Despite these treatment costs (accounting for around 7% of the Medicare budget), funding for kidney research is much less than for diseases such as cancer and HIV, working out at just $30 per patient. Despite the funding gap, researchers in regenerative medicine have made significant inroads into understanding CKD.
The Role of Stem Cells in Organ Regeneration
Stem cells are specialized cells that have the ability to proliferate and differentiate into one or more different types of cell while retaining a few unchanged, waiting to do same; their discovery and manipulation paves the way for the regeneration of human tissues and organs and, in the last decade, researchers have discovered specific types of stem cells in almost every part of the body, including the kidneys. Kidney stem cells have been found in greatest concentration behind the part of the nephron known as the Bowman’s capsule, a cup-like sac involved in the initial stages of blood filtration; renal stem cells have also been isolated among the cells of the tubules.
Building the Artificial Kidney
Understanding the role stem cells play in the development of the kidney is central to the creation of new treatments for CKD, and researchers have made significant progress in laboratory and animal studies. Some of these studies have involved induced pluripotent stem cells (iPSCs), somatic stem cells that can be engineered into an embryonic state so that they can be differentiated into a wide variety of cells without the need to use controversial embryonic stem cells (ESCs).
Some strains of stem cell research focus on exposing renal stem cells (created from iPSCs) to drugs in an attempt to improve on current CKD medications, but one of the most ambitious projects to date involves building a fully-functional artificial kidney ready for transplantation. The idea involves creating an organ scaffold which is then seeded with stem cells and nurtured to generate the necessary structures. This is an incredibly complex challenge since coaxing stem cells to become the right kind of renal cell requires intricate knowledge of the signaling processes involved in tissue generation; the choice and timing of growth factors has to be meticulously managed.
The results of scientists’ endeavours in this field have been extremely positive with one group of researchers in Massachusetts succeeding in stripping down a rat kidney, generating a new one using stem cells and transplanting the resultant organ into a living rat which went on to produce urine. It will be many years before we are close to growing a human kidney for transplantation but this is a significant step in the right direction.
A Role for Mesenchymal Stem Cells in CKD
Whereas renal stem cells are scarce, elusive and difficult to extract, mesenchymal stem cells (MSCs) are abundant in the body and relatively easily obtained from bone marrow or adipose (fat) tissue. Although MSCs are unable to directly differentiate into the highly specialized cells found in the kidney, there is sound evidence that they are capable of releasing proteins which can both stimulate the regeneration of such cells and inhibit the process of cell death that follows tissue damage. This has been witnessed in animal studies and MSCs are now sometimes incorporated into dialysis. As mentioned above, there have also been cases whereby donor MSCs have been transplanted along with a kidney, possibly eliminating the need for toxic anti-rejection drugs.
MSCs are also used in autologous stem cell treatments whereby a patient’s own stem cells are harvested, cultivated and then redeployed via injection. Such procedures require an experienced and competent therapeutic team and state-of-the-art equipment and facilities. Patients should not expect a cure for their disease but may experience an improvement in symptoms. The Mississippi Stem Cell Treatment Center extracts MSCs from stromal vascular fraction (SVF) harvested from adipose tissue. We are currently running various experimental treatments for numerous health conditions.
Although it may be overly optimistic to say that a cure for CKD is on the horizon, there is genuine hope among experts that stem cell treatments may soon be available that can significantly slow the progression of the disease. By cutting the instances of end-stage renal failure, transplant waiting lists would shrink and significant money would be saved, benefiting everyone, not least those kidney disease patients anticipating multiple visits to four-hourly dialysis treatments.
The Mississippi Stem Cell Treatment Center runs a dynamic and constantly evolving program of experimental autologous stem cell therapies. Call us on (866) 885 4823 to find out which pathologies we are currently investigating and treating. You should also pay regular visits to our website at http://www.gulfcoaststemcell.com to keep in touch with latest developments.