LONDON ¿ The story of how stem cells can turn themselves into a multitude of other body cells has taken another astonishing twist, with the discovery that stem cells from the bone marrow can migrate to the kidneys and turn into kidney cells. New ways of treating kidney diseases are likely to flow from the finding, raising hopes of better treatments for conditions, including end-stage renal failure, lupus and cancer.
Researchers funded by the Imperial Cancer Research Fund (ICRF), one of the UK¿s largest cancer research charities, confirmed their findings in mice with a study in humans. They found that male cells of a type found only in the kidneys were present in female kidneys that had been transplanted into eight human males with kidney failure.
Sir Paul Nurse, director general of the ICRF, said: ¿Ultimately, this research may one day lead to regenerating a new kidney using the patient¿s own stem cells. This would solve the desperate shortage of available kidney transplants and avoid problems with rejection. The potential for therapies is enormous and very exciting.¿
More than 5,000 people in the UK are on the waiting list for a kidney transplant, and a further 32,000 are receiving treatment, half of them to control rejection following a transplant.
Nick Wright, head of the ICRF¿s histopathology unit and warden of Queen Mary and Westfield¿s School of Medicine and Dentistry in London, said: ¿Anti-rejection medication after a kidney transplant costs about #5,000 per patient a year, and each year the number of new patients needing kidney transplants increases by about 5 percent. It would be fantastic to save kidney patients this trauma.¿
If doctors could use stem cells from the patient¿s own bone marrow to replenish kidney cells lost by injury, this would be of huge benefit to patients, as the kidney is very poor at repairing itself, Wright said.
Wright and colleagues report their results in a paper published by the Journal of Pathology online. Its title is: ¿Bone marrow contributes to renal parenchymal turnover and regeneration.¿
Richard Poulsom, a research pathologist who is head of the in situ hybridization service at ICRF and first author of the Journal of Pathology paper, told BioWorld International: ¿Many other research teams had demonstrated the amazing plasticity of stem cells being able to convert into cells of other organs, but the kidney was conspicuous by its absence.¿
He and Wright, together with collaborators based in London, set out to discover whether adult stem cells could indeed differentiate into kidney cells.
Their first experiment was carried out in mice. Female mice were irradiated to destroy their bone marrow, and immediately after were given bone marrow transplants from male donor mice. After a few weeks, they were killed, and sections from their kidneys examined.
Tests showed that, in the female mice killed 13 weeks after the bone marrow transplant, an estimated 7.9 percent of the kidney cells known as tubular epithelial cells contained a Y chromosome.
¿Further immunohistochemical and staining studies suggest to us that these cells are indistinguishable from their neighbors,¿ Poulsom said. ¿They have a metabolic enzyme that is completely appropriate for these cells in their new location, and they have cell surface proteins and sugars that are appropriate for their location.¿
The cells have either come into the kidney and divided there, and then differentiated into tubular epithelial cells, or possibly many cells have come in and individually converted into kidney cells, Poulsom added.
To confirm their findings in humans, the team obtained biopsy material from eight male patients who had received a kidney transplant from a female donor. Tests showed that it was possible to find cells containing Y chromosomes in all eight biopsies, with the estimated proportion of Y-positive tubular cells ranging from 1.8 percent to 20 percent.
Discussing their findings in the Journal of Pathology paper, the authors write: ¿Our finding that a tubular epithelial cell phenotype arises from extra-renal sources following transplantation of normal bone marrow cells into normal mice, or normal kidney into human patients, has considerable implications for both nephron cell biology and pathology, because tubular cell death is a common end-point in both acute and chronic renal disease and it has been assumed that in situ proliferation of tubular cells was the only mechanism by which regeneration could be achieved.¿
Poulsom said the team is now seeking funding to carry out studies to establish what the normal pattern of movement of stem cells from the bone marrow to the kidneys is. ¿We want to know what the normal fate of these cells is,¿ he said. ¿Do they normally just pass through the kidney? Do you need specific types of damage to the kidney to encourage passing stem cells to seed and grow?¿
If it were possible to find a population of, say, bone marrow stem cells that have a predilection for populating the kidney, this could provide a specific route for gene therapy, Poulsom said. ¿In conditions caused by mutations at single loci, it is conceivable that in the future it may be possible to replace some of the affected cells with cells containing the correct wild-type gene, through bone marrow transplantation. If you used the patient¿s own bone marrow and introduced the desired gene using a retroviral strategy, then this would avoid dependence on donated bone marrow from other people, or on embryonic stem cells.¿
In autoimmune disorders such as lupus, this strategy could be harnessed to deliver genes encoding anti-inflammatory agents, Poulsom predicted.