nidНефрология и диализNephrology and Dialysis1680-44222618-9801Российское диализное общество10.28996/1680-4422-2017-4-449-454nid-407Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESСовременное представление о ренальных стволовых клеткахThe current understanding of the renal stem cellsТодоровС. С.TodorovS. S.setodorov@yandex.ruБатюшинМ. М.BatiushinM. M.noemail@neicon.ruРостовский государственный медицинский университет, РоссияРоссияRostov state medical University, RussiaRussian Federation201716082024194449454Copyright © Тодоров С.С., Батюшин М.М., 20242024Тодоров С.С., Батюшин М.М.Todorov S.S., Batiushin M.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephro.ru/jour/article/view/407

Обсуждаются функциональные особенности, локализация ренальных стволовых клеток (РСК), их роль в механизмах репарации почки. Предполагается, что в качестве РСК могут выступать париетальные эпителиальные клетки капсулы Боумена клубочков. При этом важное значение для определения РСК имеет выявление иммунофенотипа CD24, CD133, PDX (подокаликсин). Есть указания о наличии РСК с PDX-позитивным и PDX-негативным статусом, который определяет дифференцировку их в подоциты. В канальцевом эпителии почки РСК могут трансформироваться в зрелые эпителиальные клетки путем дедифференцировки или локализоваться отдельными группами. До настоящего времени окончательно не решен вопрос о наличии РСК среди клеток эпителия извитых канальцев (КЭИК). Известно, что КЭИК являются высокоспециализированными, дифференцированными клетками, они имеют кубическую или цилиндрическую форму, полярное апикально-базальное расположение. Фенотипически КЭИК, как и подоциты, обладают низкой митотической активностью, однако в случае их повреждения в них может экпрессироваться белок cyclin D1, являющийся индикатором G1-фазы митотического цикла. Обсуждается несколько источников клеток, способных к дифференцировке в КЭИК: участие самих КЭИК в процессах регенерации, наличие единичных РСК среди КЭИК, роль экстраренальных стволовых клеток (пул пролиферации клеток). Наиболее популярной является модель развития дифференцированных КЭИК, которые проходят этап дедифференцировки. Дедифференцировка КЭИК включает переход из эпителиального в мезенхимальное состояние (эпителиально-мезенхимальный переход, ЭМП) и возврат к клеточному циклу с развитием КЭИК (мезенхимально-эпителиальный переход, МЭП). Однако остается непонятным, может ли среди образующихся КЭИК при МЭП появляться только зрелые формы клеток или отдельные из них могут сохранять свойства стволовых. Выявление различных типов РСК открывает новый этап изучения биологических закономерностей регенерации различных клеточных компонентов нефрона, что определит создание новых лекарственных препаратов, предотвратит развитие фиброза почки и почечной недостаточности.

The role, significance, the localization of renal stem cells (RSC) are discussed. It is expected that the role of RSC can act parietal epithelial cells of Bowman's capsule of glomeruli. At the same time important to determine the RSC is the identification of immunophenotype CD24, CD133, PDX. There are indications of the presence of RSC with PDX positive and negative status, which determines their differentiation in podocytes. In renal tubular epithelium RSC can be transformed into mature epithelial cells by dedifferentiation of localized or specific groups. So far, not fully resolved the issue of the presence of RSC among epithelial cells of the convoluted tubules. It is known that epithelial cells (EC) of tubules are highly specialized, differentiated epithelial cells, cubic or cylindrical, are polar apical-basal location. Phenotypically as podocytes possess low mitotic activity, but in case of damage they can express protein cyclin D1, which is an indicator of G1-phase of the mitotic cycle. We discuss several sources of cells capable of differentiating into EC. EC themselves participate in the regeneration process, among the presence of single RSC EC, extrarenal role of stem cells (a pool of cell proliferation). The most popular model is the development of differentiated EC, they pass stage of dedifferentiation. EC dedifferentiation involves a transition from an epithelial to mesenchymal state (epithelial-mesenchymal transition, EMT) and return to the cell cycle with the development EC (mesenchymal-epithelial transition MET). However, it remains unclear whether among EC produced at MET appear only mature form of cells or some of them can retain the properties of stem. Identify different types of RSC opens a new stage in the study of biological phenomena of regeneration of various cellular components of the nephron, which will determine the development of new medicines, prevent the development of renal fibrosis and renal failure.

почкаренальные стволовые клеткиподоцитыэпителий канальцевиммуногистохимиямолекулярная биологиядифференцировка клетокдедифференцировка клетокэпителиально-мезенхимальный переходфиброз почечной тканипочечная недостаточностьkidneyrenal stem cellspodocytestubular epitheliumimmunohistochemistrymolecular biologycell differentiationdedifferentiation of cellsepithelial-mesenchymal transitionrenal tissue fibrosiskidney failureReferencesBariety J., Mandet C., Hill G.S. et al. Parietal podocytes in normal human glomeruli. J.Am.Soc.Nephrol. 2006. 17: 2770-2780.Bariety J., Mandet C., Hill G.S. et al. Parietal podocytes in normal human glomeruli. J.Am.Soc.Nephrol. 2006. 17: 2770-2780.Benigni A., Morigi M., Remuzzi G. Kidney regeneration. Lancet. 2010. 375: 1310-1317.Benigni A., Morigi M., Remuzzi G. Kidney regeneration. Lancet. 2010. 375: 1310-1317.Bhathena D.B. Glomerular basement membrane length to podocyte ratio in human nephronopenia: implications for local segmental glomerulosclerosis. Am.J.Kidney Dis. 2003. 41: 1179-1188.Bhathena D.B. Glomerular basement membrane length to podocyte ratio in human nephronopenia: implications for local segmental glomerulosclerosis. Am.J.Kidney Dis. 2003. 41: 1179-1188.Davidson A.J. Uncharted waters: nephrogenesis and renal regeneration in fish ad mammals. Pediatr.Nephrol. 2011. 26: 1435-1443.Davidson A.J. Uncharted waters: nephrogenesis and renal regeneration in fish ad mammals. Pediatr.Nephrol. 2011. 26: 1435-1443.Eckfeldt C.E., Mendenhall E.M., Verfaille C.M. The molecular repertoire of the almighty stem cell. Nat.Rev.Mol.Cell Biol. 2005. 6: 726-737.Eckfeldt C.E., Mendenhall E.M., Verfaille C.M. The molecular repertoire of the almighty stem cell. Nat.Rev.Mol.Cell Biol. 2005. 6: 726-737.Graf T., Stadtfeld M. Heterogenity of embryonic and adult stem cells. Cell Stem Cell. 2008. 3: 480-483.Graf T., Stadtfeld M. Heterogenity of embryonic and adult stem cells. Cell Stem Cell. 2008. 3: 480-483.Gibson I.W., Downie I., Downie T.T. et al. The parietal podocyte: a study of the vascular pole of the human glomerulus. Kidney Int. 1992. 41: 2770-2780.Gibson I.W., Downie I., Downie T.T. et al. The parietal podocyte: a study of the vascular pole of the human glomerulus. Kidney Int. 1992. 41: 2770-2780.Gross M.L., Ritz E., Schoof A. et al. ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes. Diabetologia. 2004. 47: 316-324.Gross M.L., Ritz E., Schoof A. et al. ACE-inhibition is superior to endothelin A receptor blockade in preventing abnormal capillary supply and fibrosis of the heart in experimental diabetes. Diabetologia. 2004. 47: 316-324.Grouls S., Iglesias D.M., Wentzensen N. et al. Lineage specification of parietal epithelial cells requires b-catenin/Wnt signalling. J.Am. Soc. Nephrol. 2012. 23: 2593-2603.Grouls S., Iglesias D.M., Wentzensen N. et al. Lineage specification of parietal epithelial cells requires b-catenin/Wnt signalling. J.Am. Soc. Nephrol. 2012. 23: 2593-2603.Hanna J.H., Saha K., Jaenisch R. Pluripotency and cellular reprogramming:facts, hypothesis, unresolved issues. Cell. 2010. 143: 508-525.Hanna J.H., Saha K., Jaenisch R. Pluripotency and cellular reprogramming:facts, hypothesis, unresolved issues. Cell. 2010. 143: 508-525.Humphreys B.D., Valerius M.T., Kobayashi A. et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008. 2: 284-291.Humphreys B.D., Valerius M.T., Kobayashi A. et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell. 2008. 2: 284-291.Jaenisch R., Young R. Stem cells, the molecular circuitry of pluripotency and nu-clear reptrogramming. Cell. 2008. 132: 567-582.Jaenisch R., Young R. Stem cells, the molecular circuitry of pluripotency and nu-clear reptrogramming. Cell. 2008. 132: 567-582.Lasagni L., Romagnani P. Glomerular epithelial stem cells: the good, the bad, and the ugly. J.Am.Soc.Nephrol. 2010. 21(10): 1612-19.Lasagni L., Romagnani P. Glomerular epithelial stem cells: the good, the bad, and the ugly. J.Am.Soc.Nephrol. 2010. 21(10): 1612-19.Levey A.S., Alkins R., Coresh J. et al. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from kidney Disease improving Global Outcomes. Kidney Int. 2007. 72: 247-259.Levey A.S., Alkins R., Coresh J. et al. Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from kidney Disease improving Global Outcomes. Kidney Int. 2007. 72: 247-259.Ma I., Allan A.L. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. 2011. 7: 292-306.Ma I., Allan A.L. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. 2011. 7: 292-306.McCampbell K., Wingert R.A. Renal stem cells: fact or science fiction? Biochem. J. 2012. 444: 153-168.McCampbell K., Wingert R.A. Renal stem cells: fact or science fiction? Biochem. J. 2012. 444: 153-168.Meguid El Nahas, Bello A.K. Chronic kidney disease: the global challenge. Lancet. 2005. 365: 331-340.Meguid El Nahas, Bello A.K. Chronic kidney disease: the global challenge. Lancet. 2005. 365: 331-340.Mikkers H., Frisen J. Deconstructing stemness. EMBO J. 2005. 24: 2715-2719.Mikkers H., Frisen J. Deconstructing stemness. EMBO J. 2005. 24: 2715-2719.Morrison S.J., Spradling A.C. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008. 139: 598-611.Morrison S.J., Spradling A.C. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 2008. 139: 598-611.Poulsom R., Little M.H. Parietal epithelial cells regenerate podocytes. J. Am. Soc. Nephrol. 2009. 20: 231-233.Poulsom R., Little M.H. Parietal epithelial cells regenerate podocytes. J. Am. Soc. Nephrol. 2009. 20: 231-233.Prunotto M., Budd D.C., Meier M. et al. From acute injury to chronic disease: pathophysiological hypothesis of an epithelial / mesenchymal crosstalk alteration in CKD. Nephrol Dial Transplant. 2012. 27: iii43-iii50.Prunotto M., Budd D.C., Meier M. et al. From acute injury to chronic disease: pathophysiological hypothesis of an epithelial / mesenchymal crosstalk alteration in CKD. Nephrol Dial Transplant. 2012. 27: iii43-iii50.Quaggin S.E., Kreidberg J.A. Development of the renal glomerulus: good neighbors and good fences. Development. 2008. 135: 609-620.Quaggin S.E., Kreidberg J.A. Development of the renal glomerulus: good neighbors and good fences. Development. 2008. 135: 609-620.Ronconi E., Sagrinati C., Angelotti M.L. et al. Regeneration of glomerular podocytes by human renal progenitors. J. Am. Soc. Nephrol. 2009. 20: 322-332.Ronconi E., Sagrinati C., Angelotti M.L. et al. Regeneration of glomerular podocytes by human renal progenitors. J. Am. Soc. Nephrol. 2009. 20: 322-332.Sagrinati C., Netti G.S., Mazzinghi B. et al. Isolation and characterisation of multipotent progenitor cells from the Bowman’s capsule of adult human kidney. J.Am. Soc.Nephrol. 2006. 17: 2443-2456.Sagrinati C., Netti G.S., Mazzinghi B. et al. Isolation and characterisation of multipotent progenitor cells from the Bowman’s capsule of adult human kidney. J.Am. Soc.Nephrol. 2006. 17: 2443-2456.Shankland S.J. The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int. 2006. 69: 2131-2147.Shankland S.J. The podocyte’s response to injury: role in proteinuria and glomerulosclerosis. Kidney Int. 2006. 69: 2131-2147.Simons B.D., Clevers H. Strategies for homeostatic stem cell-renewal in adult tissues. Cell. 2011. 145: 851-862.Simons B.D., Clevers H. Strategies for homeostatic stem cell-renewal in adult tissues. Cell. 2011. 145: 851-862.Vaughan M.R., Quaggin S.E. How do mesangial and endothelial cells form the glomerular tuft? J.Am.Soc.Nephrol.2008. 19:24-33Vaughan M.R., Quaggin S.E. How do mesangial and endothelial cells form the glomerular tuft? J.Am.Soc.Nephrol.2008. 19:24-33Vogelmann S.U., Nelson W.J., Myers B.D. et al. Urinary excretion of viable podocytes in health and renal disease. Am. J. Physiol. Renal Phesiol. 2003. 285: F40-F48.Vogelmann S.U., Nelson W.J., Myers B.D. et al. Urinary excretion of viable podocytes in health and renal disease. Am. J. Physiol. Renal Phesiol. 2003. 285: F40-F48.Vogetseder A., Picard N., Gaspert A. et al. Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells. Am. J. Physiol. Cell Physiol. 2008. 294: C22-C28.Vogetseder A., Picard N., Gaspert A. et al. Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells. Am. J. Physiol. Cell Physiol. 2008. 294: C22-C28.Wiggins R.C. The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int. 2007. 71: 1205-1214.Wiggins R.C. The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int. 2007. 71: 1205-1214.Zubko R., Ftishman W. Stem cell therapy for the kidney? Am. J. Ther. 2009. 16: 247-256.Zubko R., Ftishman W. Stem cell therapy for the kidney? Am. J. Ther. 2009. 16: 247-256.

The authors declare that there are no conflicts of interest present.