Diabetes and the Kidney

Editor(s): Lai K.N. (Hong Kong) 
Tang S.C.W. (Hong Kong) 
Table of Contents
Vol. 170, 2011
Section title: Therapeutic Approach of Diabetic Nephropathy
Lai KN, Tang SCW (eds): Diabetes and the Kidney. Contrib Nephrol. Basel, Karger, 2011, vol 170, pp 228–236

Kidney Regeneration: Any Prospects?

Romagnani P.
Excellence Centre for Research, Transfer and High Education for the Development of de novo Therapies, and Meyer Children’s Hospital, Nephrology Unit, Department of Clinical Pathophysiology, University of Florence, Florence, Italy

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Chronic kidney disease is a leading cause of mortality and morbidity in western countries which affects about 11% of the adult population. With the increasing rate of chronic kidney disease and limited alternatives for its treatment, potential regenerative approaches for kidney damage are urgently needed, but are limited by the complexity of this organ. Bone marrow-derived stem cells as well as mesenchymal stem cells were envisioned for the development of this type of treatment. However, most studies suggested that these cells cannot differentiate into renal epithelial cells, and concluded that their beneficial effects are probably related to secretion of growth factors. In addition, a long-term partial maldifferentiation of injected mesenchymal stem cells into adipocytes accompanied by glomerular sclerosis was reported. The incapacity of bone marrow-derived stem cells to differentiate into renal cells suggested that turnover of resident renal epithelial cells may be related to the existence of potential stem/progenitor cells within the adult human kidney. Consistently, renal progenitors with the potential to differentiate into podocytes as well as tubular cells were recently identified at the urinary pole of the Bowman’s capsule in adult kidneys. The discovery of renal progenitors that encourage regeneration and promote functional repair of glomerular injury demonstrates that prevention and treatment of glomerulosclerosis may be possible. In addition, converging evidence suggests that the outcome of glomerular disorders depends on a balance between injury and regeneration provided by renal progenitors. In summary, understanding how self-renewal and fate decision of renal progenitors may be perturbed or modulated will be of crucial importance to obtain novel pharmacological tools for prevention and treatment of diabetic nephropathy, as well as other causes of glomerulosclerosis.

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  1. Meguid El Nahas A, Bello AK: Chronic kidney disease: The global challenge. Lancet 2005;365:331-340
  2. Tang SC: Diabetic nephropathy: a global and growing threat. Hong Kong Med J 2010;16:244-245
  3. Wiggins RC: The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 2007;71:1205-1214
  4. Kriz W, LeHir M: Pathways to nephron loss starting from glomerular diseases-insights from animal models. Kidney Int 2005;67:404-419
  5. Pagtalunan ME, Miller PL, Jumping-Eagle S, Nelson RG, Myers BD, Rennke HG, Coplon NS, Sun L, Meyer TW: Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest 1997;99:342-348
  6. White KE, Bilous RW, Marshall SM, El Nahas M, Remuzzi G, Piras G, De Cosmo S, Viberti G: The European Study for the Prevention of Renal Disease in Type I diabetes (ESPRIT): podocyte number in normotensive type I diabetic patients with albuminuria. Diabetes 2002;51:3083-3089
  7. Dalla Vestra M, Masiero A, Roiter AM, Saller A, Crepaldi G, Fioretto P: Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes 2003;52:1031-1035
  8. Lemley KV, Lafayette RA, Safai M, Derby G, Blouch K, Squarer A, Myers BD: Podocytopenia and disease severity in IgA nephropathy. Kidney Int 2002;61:1475-1485
  9. Fioretto P, Steffes MW, Sutherland DE, Goetz FC, Mauer M: Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998;339:69-75
  10. Remuzzi G, Benigni A, Remuzzi A: Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest 2006;116:288-296
  11. Blanpain C, Horsley V, Fuchs E: Epithelial stem cells: turning over new leaves. Cell 2007;128:445-458
  12. Sagrinati C, Ronconi E, Lazzeri E, Lasagni L, Romagnani P: Stem-cell approaches for kidney repair: choosing the right cells. Trends Mol Med 2008;14:277-285
  13. Kale S, Karihaloo A, Clark PR, Kashgarian M, Krause DS, Cantley LG: Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J Clin Invest 2003;112:42-49
  14. Lin F, Moran A, Igarashi P: Intrarenal cells, not bone marrow-derived cells, are the major source for regeneration in post ischemic kidney. J Clin Invest 2005;115:1756-1764
  15. Duffield JS, Park KM, Hsiao LL, Kelley VR, Scadden DT, Ichimura T, Bonventre JV: Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells. J Clin Invest 2005;115:1743-1755
  16. Sugimoto H, Mundel TM, Sund M, Xie L, Cosgrove D, Kalluri R: Bone-marrowderived stem cells repair basement membrane collagen defects and reverse genetic kidney disease. Proc Natl Acad Sci USA 2006;103:7321-7326
  17. Imberti B, Morigi M, Tomasoni S, Rota C, Corna D, Longaretti L, Rottoli D, Valsecchi F, Benigni A, Wang J, Abbate M, Zoja C, Remuzzi G: Insulin-like growth factor-1 sustains stem cell mediated renal repair. J Am Soc Nephrol 2007;18:2921-2928
  18. Tögel F, Weiss K, Yang Y, Hu Z, Zhang P, Westenfelder C: Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am J Physiol Renal Physiol 2007;292:F1626-F1635
  19. Kunter U, Rong S, Boor P, Eitner F, Müller-Newen G, Djuric Z, van Roeyen CR, Konieczny A, Ostendorf T, Villa L, Milovanceva-Popovska M, Kerjaschki D, Floege J: Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes. J Am Soc Nephrol 2007;18:1754-1764
  20. Prodromidi EI, Poulsom R, Jeffery R, Roufosse CA, Pollard PJ, Pusey CD, Cook HT: Bone marrow-derived cells contribute to podocyte regeneration and amelioration of renal disease in a mouse model of Alport syndrome. Stem Cells 2006;24:2448-2455
  21. Ninichuk V, Gross O, Segerer S, Hoffmann R, Radomska E, Buchstaller A, Huss R, Akis N, Schlöndorff D, Anders HJ: Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice. Biol Blood Marrow Transplant 2008;14:631-640
  22. Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, Prockop DJ: Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci USA 2006;103:17438-17443
  23. Amin AH, Abd Elmageed ZY, Nair D, Partyka MI, Kadowitz PJ, Belmadani S, Matrougui K: Modified multipotent stromal cells with epidermal growth factor restore vasculogenesis and blood flow in ischemic hind-limb of type II diabetic mice. Lab Invest 2010;90:985-996
  24. Volarevic V, Arsenijevic N, Lukic ML, Stojkovic M: Mesenchymal stem cell treatment of complications of diabetes mellitus. Stem Cells 2010;Epub ahead of print
  25. Sagrinati C, Netti GS, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, Ronconi E, Meini C, Gacci M, Squecco R, Carini M, Gesualdo L, Francini F, Maggi E, Annunziato F, Lasagni L, Serio M, Romagnani S, Romagnani P: Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys. J Am Soc Nephrol 2006;17:2443-2456
  26. Romagnani P: Toward the identification of a ‘renopoietic system ?. Stem Cells 2009;27:2247-2253
  27. Ronconi E, Sagrinati C, Angelotti ML, Lazzeri E, Mazzinghi B, Ballerini L, Parente E, Becherucci F, Gacci M, Carini M, Maggi E, Serio M, Vannelli GB, Lasagni L, Romagnani S, Romagnani P: Regeneration of glomerular podocytes by human renal progenitors. J Am Soc Nephrol 2009;20:322-332
  28. Appel D, Kershaw D, Smeets B, Yuan G, Fuss A, Frye B, Elger M, Kriz W, Floege J: Moeller MJ: Recruitment of podocytes from glomerular parietal epithelial cells. J Am Soc Nephrol 2009;20:333-343
  29. Lasagni L, Romagnani P: Glomerular epithelial stem cells: the good, the bad and the ugly. J Am Soc Nephrol 2010;21:1612-1619
  30. Najafian B, Kim Y, Crosson JT, Mauer M: Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy. J Am Soc Nephrol 2003;14:908-917

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