Artificial kidney – step by step
American scientists have grown kidney tubule cells from stem cells
LifeSciencesToday based on Harvard Stem Cell Institute: HSCI researchers generate kidney tubular cells from stem cellsScientists at the Harvard Stem Cell Institute have achieved differentiation of stem cells into renal tubule cells.
This is a significant step forward towards the treatment of kidney failure by regenerative medicine methods, which in the future should replace dialysis and transplantation. The results of the study are published in the Journal of the American Society of Nephrology (Lam et al., Rapid and Efficient Differentiation of Human Pluripotent Stem Cells into Intermediate Mesoderm That Forms Tubes Expressing Kidney Proximal Tubular Markers).
Chronic kidney disease is one of the global public health problems. With the progression of the disease to the stage of renal failure, the choice of treatment options is limited to dialysis and kidney transplantation. Regenerative medicine, which involves restoring a tissue or organ or replacing them with new ones, can be a promising alternative.
The head of the study, Joseph Bonventre, MD, PhD, and his colleagues have been developing a strategy for differentiating human pluripotent – embryonic and induced – stem cells into kidney cells for the past five years.
"Our goal was to develop a simple, effective and reproducible method of differentiating human pluripotent stem cells into cells of the intermediate mesoderm – the earliest tissue of the developing embryo, which is destined to develop into kidneys," first author Albert Lam, MD, comments on the study, noting that these cells will become "starting blocks" for obtaining more specialized kidney cells.
Researchers have developed a cocktail of chemicals that, when added to stem cells, causes them to turn off the genes of embryonic stem cells and turn on the genes of kidney cells in the same sequence as it occurs during the embryonic development of the organ.
The researchers were able to differentiate both embryonic and induced human pluripotent stem cells into cells expressing PAX2 and LHX1, two key markers of intermediate mesoderm.
Human pluripotent stem cells differentiated into cells,
expressing markers of the intermediate mesoderm.
Cells expressing PAX2 are marked green, those expressing LHX1 are marked red.
(Photo: Bonventre Lab)
Induced pluripotent stem cells were obtained by reprogramming fibroblasts taken from biopsy skin samples, which makes this method applicable in personalized medicine, where the original cells can be obtained from skin cells of a particular patient. These differentiated cells expressed several genes characteristic of the intermediate mesoderm and could spontaneously give rise to tubular structures expressing markers of mature renal tubules. The researchers then differentiated them into cells expressing SIX2, SALL1 and WT1, important markers of metanephric cap mesenchyma, a critical stage of kidney differentiation. During embryonic development, the compacted metanephric mesenchyme contains a population of progenitor cells that give rise to almost all epithelial cells of the kidney.
Diagram from an article in the Journal of the American Society of Nephrology
When transplanted into adult or embryonic mouse kidneys, these cells continue to behave like kidney cells, giving hope that scientists will someday be able to create kidney tissues capable of functioning in the patient's body with 100 percent immune compatibility.
"We believe that the successful production of kidney progenitor cells or functional kidney cells from human pluripotent stem cells will have a huge impact on a number of clinical and translational applications, including bioengineering of renal tissues, the development of assistive devices for the treatment of acute and chronic kidney disease, drug toxicity assessment, screening of new drugs and modeling of human kidney diseases", – concludes Dr. Lam.
Portal "Eternal youth" http://vechnayamolodost.ru24.12.2013