Skip to main content
SpringerLink
Log in
Book cover

Stem Cells Heterogeneity - Novel Concepts pp 195–216Cite as

The Heterogeneity of Renal Stem Cells and Their Interaction with Bio- and Nano-materials

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1123))

Abstract

For a long time, the kidney has been considered incapable of regeneration. Instead, in recent years, studies have supported the existence of heterogeneity of renal stem/progenitor cells with the ability to regenerate both glomerular and tubular epithelial cells. Indeed, several studies evidence that renal progenitor cells, releasing chemokines, growth factors, microvesicles, and transcription factors through paracrine mechanisms, can induce tissue regeneration and block pathological processes of the kidney. In this chapter the potentiality of the kidney regenerative processes is considered and reviewed, and the main classes of stem/progenitor cells that might contribute to the renal tissue renewal is analyzed. Moreover, we evaluate the role of biomaterials in the regulation of cellular functions, specifically addressing renal stem/progenitor cells. Materials can be synthesized and tailored in order to recreate a finely structured microenvironment (by nanostructures, nanofibers, bioactive compounds, etc.) with which the cells can interact actively. For instance, by patterning substrates in regions that alternately promote or prevent protein adsorption, cell adhesion and spreading processes can be controlled in space. We illustrate the potentiality of nanotechnologies and engineered biomaterials in affecting and enhancing the behavior of renal stem/progenitor cells. Although there are still many challenges for the translation of novel therapeutics, advances in biomaterials and nanomedicine have the potential to drastically change the clinical and therapeutic landscape, even in combination with stem cell biology.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Remuzzi G, Benigni A, Remuzzi A (2006) Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest, 116:288-96. doi: https://doi.org/10.1172/JCI27699

  2. Wiggins R-C (2007) The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 71:1205–1214

    Article  CAS  Google Scholar 

  3. Reimschuessel R (2001) A fish model of renal regeneration and development. ILAR J 42:285–291

    Article  CAS  Google Scholar 

  4. Elger M, Hentschel H, Litteral J, Wellner M, Kirsch T, Luft FC, Haller H (2003) Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea. J Am Soc Nephrol 14:1506–1518

    Article  Google Scholar 

  5. Reimschuessel R, Bennett RO, May EB, Lipsky MM (1990) Development of newly formed nephrons in the goldfish kidney following hexachlorobutadiene-induced nephrotoxicity. Toxicol Pathol 18:32–38

    Article  CAS  Google Scholar 

  6. Lazzeri E, Angelotti ML, Peired A et al (2018) Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury. Nat Commun 9:1344

    Article  Google Scholar 

  7. Rinkevich Y, Montoro DT, Contreras-Trujillo H et al (2014) In vivo clonal analysis reveals lineage-restricted progenitor characteristics in mammalian kidney development, maintenance, and regeneration. Cell Rep 7:1270–1283

    Article  CAS  Google Scholar 

  8. Schedl A (2007) Renal abnormalities and their developmental origin. Nat Rev Genet 8:791–802

    Article  CAS  Google Scholar 

  9. Dressler GR (2006) The cellular basis of kidney development. Annu Rev Cell Dev Biol 22:509–529

    Article  CAS  Google Scholar 

  10. Romagnani P, Lasagni L, Remuzzi G (2013) Renal progenitors: an evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol. https://doi.org/10.1038/nrneph.2012.290

  11. Kobayashi A, Valerius MT, Mugford JW, Carroll TJ, Self M, Oliver G, McMahon AP (2008) Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3:169–181

    Article  CAS  Google Scholar 

  12. Kubota H, Avarbock MR, Brinster RL (2003) Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci 100:6487–6492

    Article  CAS  Google Scholar 

  13. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat M-L, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88

    Article  CAS  Google Scholar 

  14. Kozakowski N, Soleiman A, Pammer J (2008) BMI-1 expression is inversely correlated with the grading of renal clear cell carcinoma. Pathol Oncol Res 14:9–13

    Article  CAS  Google Scholar 

  15. Rajasekhar VK, Begemann M (2007) Concise review: roles of polycomb group proteins in development and disease: a stem cell perspective. Stem Cells 25:2498–2510

    Article  CAS  Google Scholar 

  16. Pesce M, Schöler HR (2001) Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells 19:271–278

    Article  CAS  Google Scholar 

  17. Imgrund M, Gröne E, Gröne HJ, Kretzler M, Holzman L, Schlöndorff D, Rothenpieler UW (1999) Re-expression of the developmental gene Pax-2 during experimental acute tubular necrosis in mice. Kidney Int 56:1423–1431. https://doi.org/10.1046/j.1523-1755.1999.00663.x

    Article  CAS  PubMed  Google Scholar 

  18. Lazzeri E, Crescioli C, Ronconi E et al (2007) Regenerative potential of embryonic renal multipotent progenitors in acute renal failure. J Am Soc Nephrol 18:3128–3138

    Article  CAS  Google Scholar 

  19. Sallustio F, De Benedictis L, Castellano G, Zaza G, Loverre A, Costantino V, Grandaliano G, Schena FP (2010) TLR2 plays a role in the activation of human resident renal stem/progenitor cells. FASEB J 24:514–525. https://doi.org/10.1096/fj.09-136481

    Article  CAS  PubMed  Google Scholar 

  20. Bussolati B, Bruno S, Grange C, Buttiglieri S, Deregibus MC, Cantino D, Camussi G (2005) Isolation of renal progenitor cells from adult human kidney. Am J Pathol 166:545–555

    Article  CAS  Google Scholar 

  21. Baud L, Haymann JP, Bellocq A, Fouqueray B (2005) Contribution of stem cells to renal repair after ischemia/reperfusion. Bull Acad Natl Med 189:634–635

    Google Scholar 

  22. Brenner BM, Cooper ME, de Zeeuw D et al (2001) Effects of losartan on renal and cardiovascular outcomes in patients with Type 2 diabetes and nephropathy. N Engl J Med 345:861–869

    Article  CAS  Google Scholar 

  23. Adamczak M, Gross M-L, Krtil J, Koch A, Tyralla K, Amann K, Ritz E (2003) Reversal of glomerulosclerosis after high-dose enalapril treatment in subtotally nephrectomized rats. J Am Soc Nephrol 14:2833–2842

    Article  CAS  Google Scholar 

  24. Remuzzi A, Gagliardini E, Sangalli F, Bonomelli M, Piccinelli M, Benigni A, Remuzzi G (2006) ACE inhibition reduces glomerulosclerosis and regenerates glomerular tissue in a model of progressive renal disease. Kidney Int 69:1124–1130

    Article  CAS  Google Scholar 

  25. Gagliardini E, Corna D, Zoja C et al (2009) Unlike each drug alone, lisinopril if combined with avosentan promotes regression of renal lesions in experimental diabetes. Am J Physiol 297:F1448–F1456

    CAS  Google Scholar 

  26. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 329:1456–1462

    Article  CAS  Google Scholar 

  27. Fioretto P, Steffes MW, Sutherland DER, Goetz FC, Mauer M (1998) Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 339:69–75

    Article  CAS  Google Scholar 

  28. HISHIKAWA K, FUJITA T (2006) Stem cells and kidney disease. Hypertens Res 29:745–749

    Article  CAS  Google Scholar 

  29. Hopkins C, Li J, Rae F, Little MH (2009) Stem cell options for kidney disease. J Pathol. https://doi.org/10.1002/path.2477

  30. Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q (2004) The renal papilla is a niche for adult kidney stem cells. J Clin Invest. https://doi.org/10.1172/JCI20921

  31. Little MH (2006) Regrow or repair: potential regenerative therapies for the kidney. J Am Soc Nephrol 17:2390–2401

    Article  Google Scholar 

  32. Sagrinati C, Netti GS, Mazzinghi B et al (2006) Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J Am Soc Nephrol 17:2443–2456

    Article  CAS  Google Scholar 

  33. Loverre A, Capobianco C, Ditonno P, Battaglia M, Grandaliano G, Schena FP (2008) Increase of proliferating renal progenitor cells in acute tubular necrosis underlying delayed graft function. Transplantation 85:1112–1119

    Article  Google Scholar 

  34. Romagnani P (2009) Toward the identification of a “renopoietic system”? Stem Cells 27:2247–2253

    Article  Google Scholar 

  35. Ronconi E, Sagrinati C, Angelotti ML et al (2009) Regeneration of glomerular podocytes by human renal progenitors. J Am Soc Nephrol 20:322–332

    Article  CAS  Google Scholar 

  36. Sallustio F, Serino G, Schena FP (2015) Potential reparative role of resident adult renal stem/progenitor cells in acute kidney injury. Biores Open Access 4:326–333

    Article  CAS  Google Scholar 

  37. Sallustio F, Serino G, Costantino V, Curci C, Cox SN, De Palma G, Schena FP (2013) miR-1915 and miR-1225-5p regulate the expression of CD133, PAX2 and TLR2 in adult renal progenitor cells. PLoS One 10:e0128258. https://doi.org/10.1371/journal.pone.0068296

    Article  CAS  Google Scholar 

  38. Procino G, Mastrofrancesco L, Sallustio F, Costantino V, Barbieri C, Pisani F, Schena FP, Svelto M, Valenti G (2011) AQP5 is expressed in type-B intercalated cells in the collecting duct system of the rat, mouse and human kidney. Cell Physiol Biochem 28:683–692. https://doi.org/10.1159/000335762

    Article  CAS  PubMed  Google Scholar 

  39. Benigni A, Morigi M, Rizzo P, Gagliardini E, Rota C, Abbate M, Ghezzi S, Remuzzi A, Remuzzi G (2011) Inhibiting angiotensin-converting enzyme promotes renal repair by limiting progenitor cell proliferation and restoring the glomerular architecture. Am J Pathol 179:628–638

    Article  Google Scholar 

  40. Angelotti ML, Ronconi E, Ballerini L et al (2012) Characterization of renal progenitors committed toward tubular lineage and their regenerative potential in renal tubular injury. Stem Cells 30:1714–1725

    Article  CAS  Google Scholar 

  41. Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, McMahon AP, Bonventre JV (2008) Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell 2:284–291

    Article  CAS  Google Scholar 

  42. Sallustio F, Curci C, Aloisi A et al (2017) Inhibin-A and decorin secreted by human adult renal stem/progenitor cells through the TLR2 engagement induce renal tubular cell regeneration. Sci Rep 7:8225. https://doi.org/10.1038/s41598-017-08474-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Castelletto L, Goya RG (1990) Sex-related incidence of tubular metaplasia in Bowman’s capsule of aging rats. Virchows Arch B Cell Pathol Incl Mol Pathol 59:79–82

    Article  CAS  Google Scholar 

  44. Andrews PM (1981) The presence of proximal tubulelike cells in the kidney parietal epithelium in response to unilateral nephrectomy. Anat Rec 200:61–65

    Article  CAS  Google Scholar 

  45. Langworthy M, Zhou B, de Caestecker M, Moeckel G, Baldwin HS (2009) NFATc1 identifies a population of proximal tubule cell progenitors. J Am Soc Nephrol 20:311–321

    Article  CAS  Google Scholar 

  46. Walker B, Mouton CP (2006) Nanotechnology and nanomedicine: a primer. J Natl Med Assoc 98:1985–1988

    PubMed  PubMed Central  Google Scholar 

  47. Wagner V, Dullaart A, Bock AK, Zweck A (2006) The emerging nanomedicine landscape. Nat Biotechnol 24:1211–1217. https://doi.org/10.1038/nbt1006-1211

    Article  CAS  PubMed  Google Scholar 

  48. Caruthers SD, Wickline SA, Lanza GM (2007) Nanotechnological applications in medicine. Curr Opin Biotechnol 18:26–30. https://doi.org/10.1016/j.copbio.2007.01.006

    Article  CAS  PubMed  Google Scholar 

  49. Svenson S (2013) Theranostics: are we there yet? Mol Pharm 10:848–856

    Article  CAS  Google Scholar 

  50. Lee DY, Li KCP (2011) Molecular theranostics: a primer for the imaging professional. Am J Roentgenol 197:318–324. https://doi.org/10.2214/AJR.11.6797

    Article  Google Scholar 

  51. De Jong WH, Borm PJ a (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine, 3:133-149. doi: https://doi.org/10.2147/IJN.S596

  52. Cho K, Wang X, Nie S, Chen ZG, Shin DM (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14:1310–1316. https://doi.org/10.1158/1078-0432.CCR-07-1441

    Article  CAS  PubMed  Google Scholar 

  53. Huang Y, Fan C-Q, Dong H, Wang S-M, Yang X-C, Yang S-M (2017) Current applications and future prospects of nanomaterials in tumor therapy. Int J Nanomed 12:1815–1825

    Article  CAS  Google Scholar 

  54. Min Y, Caster JM, Eblan MJ, Wang AZ (2015) Clinical translation of nanomedicine. Chem Rev 115:11,147–11,190. https://doi.org/10.1021/acs.chemrev.5b00116

    Article  CAS  Google Scholar 

  55. Caster JM, Patel AN, Zhang T, Wang A (2017) Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials. Wiley Interdiscip Rev Nanomed Nanobiotechnol. https://doi.org/10.1002/wnan.1416

  56. Li J, Mooney DJ (2016) Designing hydrogels for controlled drug delivery. Nat Rev Mater. https://doi.org/10.1038/natrevmats.2016.71

  57. Peng E, Wang F, Xue JM (2015) Nanostructured magnetic nanocomposites as MRI contrast agents. J Mater Chem B 3:2241–2276. https://doi.org/10.1039/C4TB02023E

    Article  CAS  Google Scholar 

  58. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J (2015) Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J Control Release 200:138–157. https://doi.org/10.1016/j.jconrel.2014.12.030

    Article  CAS  PubMed  Google Scholar 

  59. Giancotti FG (1999) Integrin Signaling. Science. 285:1028–1032. https://doi.org/10.1126/science.285.5430.1028

  60. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–687. https://doi.org/10.1016/S0092-8674(02)00971-6

    Article  CAS  PubMed  Google Scholar 

  61. Beningo KA, Dembo M, Wang Y -l. (2004) Responses of fibroblasts to anchorage of dorsal extracellular matrix receptors. Proc Natl Acad Sci 101:18,024–18,029. https://doi.org/10.1073/pnas.0405747102

    Article  CAS  Google Scholar 

  62. Ramakrishna S, Mayer J, Wintermantel E, Leong KW (2001) Biomedical applications of polymer-composite materials: a review. Compos Sci Technol 61:1189–1224. https://doi.org/10.1016/S0266-3538(00)00241-4

    Article  CAS  Google Scholar 

  63. Daglar B, Ozgur E, Corman ME, Uzun L, Demirel GB (2014) Polymeric nanocarriers for expected nanomedicine: current challenges and future prospects. RSC Adv 4:48,639–48,659. https://doi.org/10.1039/c4ra06406b

    Article  CAS  Google Scholar 

  64. de Las Heras Alarcon C, Pennadam S, Alexander C (2005) Stimuli responsive polymers for biomedical applications. Chem Soc Rev 34:276–285. https://doi.org/10.1039/b406727d

    Article  CAS  PubMed  Google Scholar 

  65. Gentile P, Chiono V, Carmagnola I, Hatton PV (2014) An overview of poly(lactic-co-glycolic) Acid (PLGA)-based biomaterials for bone tissue engineering. Int J Mol Sci 15:3640–3659. https://doi.org/10.3390/ijms15033640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tibbitt MW, Rodell CB, Burdick JA, Anseth KS (2015) Progress in material design for biomedical applications. Proc Natl Acad Sci 112:14,444–14,451. https://doi.org/10.1073/pnas.1516247112

    Article  CAS  Google Scholar 

  67. Mahmoud Abbas AO (2010) Chitosan for biomedical applications. Univ Iowa. https://doi.org/10.3390/ma2020374

  68. Mano JF (2008) Stimuli-responsive polymeric systems for biomedical applications. Adv Eng Mater 10:515–527. https://doi.org/10.1002/adem.200700355

    Article  CAS  Google Scholar 

  69. Pařzek M, Novotná K, Bačáková L (2011) The role of smooth muscle cells in vessel wall pathophysiology and reconstruction using bioactive synthetic polymers. Physiol Res 60:419–437

    Google Scholar 

  70. Neyra MP. Interactions between titanium surfaces and biological components. PhD Thesis Dissertation 2009

    Google Scholar 

  71. Maheshwari G, Brown G, Lauffenburger DA, Wells A, Griffith LG (2000) Cell adhesion and motility depend on nanoscale RGD clustering. J Cell Sci 113:1677–1686. https://doi.org/10.1083/jcb.144.5.1019

    Article  CAS  Google Scholar 

  72. DeLong SA, Gobin AS, West JL (2005) Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration. J Control Release 109:139–148. https://doi.org/10.1016/j.jconrel.2005.09.020

    Article  CAS  PubMed  Google Scholar 

  73. Sciancalepore AG, Portone A, Moffa M, Persano L, De Luca M, Paiano A, Sallustio F, Schena FP, Bucci C, Pisignano D (2016) Micropatterning control of tubular commitment in human adult renal stem cells. Biomaterials 94:57–69. https://doi.org/10.1016/j.biomaterials.2016.03.042

    Article  CAS  PubMed  Google Scholar 

  74. Sciancalepore AG, Sallustio F, Girardo S, Passione LG, Camposeo A, Mele E, Lorenzo MD, Costantino V, Schena FP, Pisignano D (2014) A bioartificial renal tubule device embedding human renal stem/progenitor cells. PLoS One 10:e0128261. https://doi.org/10.1371/journal.pone.0087496

    Article  CAS  Google Scholar 

  75. Khong TT, Aarstad OA, Skjåk-Bræk G, Draget KI, Vårum KM (2013) Gelling concept combining chitosan and alginate—proof of principle. Biomacromolecules 14:2765–2771

    Article  CAS  Google Scholar 

  76. Sciancalepore AG, Moffa M, Iandolo D, Netti GS, Prattichizzo C, Grandaliano G, Lucarelli G, Cormio L, Gesualdo L, Pisignano D Aligned nanofiber topographies enhance the differentiation of adult renal stem cells into glomerular podocytes. Adv Eng Mater 20:1800003

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, Bari, Italy

    Fabio Sallustio

  2. Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, Bari, Italy

    Fabio Sallustio & Loreto Gesualdo

  3. Dipartimento di Fisica ‘E. Fermi’, University of Pisa, Pisa, Italy

    Dario Pisignano

  4. NEST CNR-Istituto Nanoscienze Piazza S. Silvestro 12, Pisa, Italy

    Dario Pisignano

Authors
  1. Fabio Sallustio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Loreto Gesualdo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dario Pisignano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabio Sallustio .

Editor information

Editors and Affiliations

  1. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Alexander Birbrair

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sallustio, F., Gesualdo, L., Pisignano, D. (2019). The Heterogeneity of Renal Stem Cells and Their Interaction with Bio- and Nano-materials. In: Birbrair, A. (eds) Stem Cells Heterogeneity - Novel Concepts. Advances in Experimental Medicine and Biology, vol 1123. Springer, Cham. https://doi.org/10.1007/978-3-030-11096-3_12

Download citation

Publish with us

Policies and ethics

Search

Navigation