Current Medicine Research and Practice (Jan 2013)
Renal progenitor cells: Characterization and genetic manipulations
Abstract
In spite of advances in modern clinical nephrology, progressive renal diseases remain incurable disorders lacking specific therapeutic approaches. It is estimated that 45,000 patients with ESRD (end-stage renal disease) require haemodialysis, with only around one quarter of the population having benefited from a renal transplant. The statistics for patients suffering from ARF (acute renal failure) are even worse. ARF develops predominantly due to injury and necrosis of renal proximal tubule cells (RPTCs) as a result of an ischaemic insult. The cause of death subsequent to ARF is generally the development of systematic inflammatory response syndrome, frequently secondary to bacterial infection or sepsis, resulting in cardiovascular collapse and ischaemic damage to the vital organs, culminating in multiorgan failure (MOF). Patients with ESRD require renal replacement therapy such as haemodialysis or peritoneal dialysis or kidney transplantations. However, haemodialysis or peritoneal dialysis does not fully compensate for the loss of kidney function over long time. They are often accompanied with cardiovascular complications and a kidney transplant recipient may undergo some complications because of immunosuppressive reagents used. There is growing recognition that the disease state arising from renal failure is the result of more than just the lack of blood volume recognition, small solute and toxin clearance that are replaced by conventional dialysis therapy. The role of kidney in the reclamation of metabolic substrates, synthesis of glutathione and free radicals, scavenging enzymes, glucogenesis, ammoniagenesis, catabolism of peptide hormones and growth factors and the production and regulation of multiple cytokines critical to inflammation and immunogenicity are not addressed by current treatment modalities. Thus, there are efforts to develop improved therapies for renal failure with the capacity to replace a wide range of kidney’s function, thereby reducing morbidity, mortality and overall economic impact associated with this condition. Such an ambition lies beyond the reach of conventional medicine. Into this expanding field of cell therapy, gene therapy offers the promise of harnessing the native abilities of the cell.
