Stem cell therapy, also known as regenerative medicine, builds on the capacity of stem cells or their derivatives to repair and replace diseased, dysfunctional or injured tissue in humans. It is a promising frontier in organ transplantation by using cells grown in a laboratory instead of donor organs, which are limited in supply. A new study recently published in STEM CELLS Translational Medicine (SCTM) appears to show that the CD133 molecule is a promising stem cell candidate in the quest for kidney repair.
Damage to renal tissue due to ischemic or toxic agents results in reduction or loss of kidney function, a pathology associated with high morbidity and mortality. After injury or disease, renal tissue may repair to some degree and regain some function, but permanent damage remains and, after repeated injury, may lead to chronic renal failure.
The team led by Dr. Benedetta Bussolati at the University of Torino’s Molecular Biotechnology Centre in Italy discovered renal stem/progenitor cells as far back as 2005—scattered cells in the human adult kidney that displayed a regenerative capacity following renal damage. These progenitor cells, characterized by the expression of the CD133 molecule, were a small group scattered along the tubules—cells proving able to survive after injury and to generate different types of renal cells. The more recent study published in SCTM took that knowledge further, exploring the roles that CD133 played in human tissue.
“In the human kidney, the expression of CD133 characterizes a population of cells with the ability to proliferate, with the added benefit of showing a resistance to damage,” said Bussolati, the SCTM study’s lead investigator. “But not much was known about how CD133 functions, so we aimed to evaluate this, as well as CD133's possible implication in the repair process. Our latest study was designed with the aim to get further knowledge on the nature of the CD133 progenitor cells for studies in regenerative medicine. In fact, few studies addressed the role of these cells in human tissues, whereas the studies in murine tissue are easier to perform. As these cells express CD133, a membrane molecule previously considered just a marker, we aimed to investigate its function and its possible modulation.”
They studied the effect of a chemotherapy drug called cisplatin, which contributed to nephrotoxicity in up to 30 percent of cases. The team showed that CD133 is a key factor in the recovery of the cells after the chemo-inflicted damage. Interestingly, they found that CD133 needs to be downregulated to allow β-catenin signaling, which can control cell proliferation, survival, cell behavior and cell fate in both embryos and adults. Moreover, they found that the molecule prevents the aging of the progenitor cells, a key finding that counteracts the exhaustion of progenitor cells in the kidney after repeated injuries.
“This is an interesting and novel finding,” commented Dr. Anthony Atala, editor-in-chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “Because the work identifies mechanisms potentially involved in the repair of tissue after injury, it suggests the possibility of new therapies for tissue repair and regeneration.”
This research opens two different fields of interest, one regarding regenerative medicine and the other regarding biomarkers. Regarding the potential for stem cell therapy, the direct application of cells with regenerative properties reinforce the efficacy of cell therapy using CD133 cells in murine models of acute and chronic renal damage. As renal progenitors are committed to the kidney cell progeny, they could obviate the potential development of inappropriate cell types, representing the ideal cell type to obtain clinically relevant beneficial effects in patients with renal failure.
“In addition,” asserts Bussolati, “CD133 cells might be even isolated from the urine. In-vitro expanded renal cells have been directly injected into the renal parenchyma showing benefit in models of chronic renal failure. This strategy has also been recently tested in a Phase 1 trial in human patients suffering chronic renal failure using expanded autologous renal cells, and two trials are ongoing in patients with diabetic chronic kidney disease.”
The Italian study also suggests a potential utility in using CD133 as biomarker for tissue regeneration and potentially for renal transplantation. They found that because CD133 is released on exosomes, small round vesicles released by cells including those along the nephron, the identification of CD133 expressing exosomes in the urine could represent new biomarker for renal damage and regeneration.
“In fact, the possibility to predict the status of the transplanted tissue in terms of the intrarenal adaptive repairing processes occurring after the transplant would be a frontier in the transplant field,” says Bussolati. “In this moment, nephrologists only rely on functional parameters, but they do not have information whether in the long run the kidney has the ability to completely regenerate or if it will undergo senescence.”