Human amniotic fluid stem cell preconditioning improves their regenerative potential

Cinzia Rota, Barbara Imberti, Michela Pozzobon, Martina Piccoli, Paolo De Coppi, Anthony Atala, Elena Gagliardini, Christodoulos Xinaris, Valentina Benedetti, Aline S C Fabricio, Elisa Squarcina, Mauro Abbate, Ariela Benigni, Giuseppe Remuzzi, Marina Morigi

Research output: Contribution to journalArticle

Abstract

Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning.

Original languageEnglish
Pages (from-to)1911-1923
Number of pages13
JournalStem Cells and Development
Volume21
Issue number11
DOIs
Publication statusPublished - Jul 20 2012

Fingerprint

Amniotic Fluid
Stem Cells
Glial Cell Line-Derived Neurotrophic Factor
Kidney
Acute Kidney Injury
Cisplatin
Multipotent Stem Cells
Chemokine CXCL12
Adult Stem Cells
Embryonic Stem Cells
Cell- and Tissue-Based Therapy
Vascular Endothelial Growth Factor A
Regeneration
Interleukin-6
Cell Survival
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Wounds and Injuries

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Human amniotic fluid stem cell preconditioning improves their regenerative potential. / Rota, Cinzia; Imberti, Barbara; Pozzobon, Michela; Piccoli, Martina; De Coppi, Paolo; Atala, Anthony; Gagliardini, Elena; Xinaris, Christodoulos; Benedetti, Valentina; Fabricio, Aline S C; Squarcina, Elisa; Abbate, Mauro; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina.

In: Stem Cells and Development, Vol. 21, No. 11, 20.07.2012, p. 1911-1923.

Research output: Contribution to journalArticle

Rota, C, Imberti, B, Pozzobon, M, Piccoli, M, De Coppi, P, Atala, A, Gagliardini, E, Xinaris, C, Benedetti, V, Fabricio, ASC, Squarcina, E, Abbate, M, Benigni, A, Remuzzi, G & Morigi, M 2012, 'Human amniotic fluid stem cell preconditioning improves their regenerative potential', Stem Cells and Development, vol. 21, no. 11, pp. 1911-1923. https://doi.org/10.1089/scd.2011.0333
Rota C, Imberti B, Pozzobon M, Piccoli M, De Coppi P, Atala A et al. Human amniotic fluid stem cell preconditioning improves their regenerative potential. Stem Cells and Development. 2012 Jul 20;21(11):1911-1923. https://doi.org/10.1089/scd.2011.0333
Rota, Cinzia ; Imberti, Barbara ; Pozzobon, Michela ; Piccoli, Martina ; De Coppi, Paolo ; Atala, Anthony ; Gagliardini, Elena ; Xinaris, Christodoulos ; Benedetti, Valentina ; Fabricio, Aline S C ; Squarcina, Elisa ; Abbate, Mauro ; Benigni, Ariela ; Remuzzi, Giuseppe ; Morigi, Marina. / Human amniotic fluid stem cell preconditioning improves their regenerative potential. In: Stem Cells and Development. 2012 ; Vol. 21, No. 11. pp. 1911-1923.
@article{f4942b0171fe40c6a568eee192423616,
title = "Human amniotic fluid stem cell preconditioning improves their regenerative potential",
abstract = "Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning.",
author = "Cinzia Rota and Barbara Imberti and Michela Pozzobon and Martina Piccoli and {De Coppi}, Paolo and Anthony Atala and Elena Gagliardini and Christodoulos Xinaris and Valentina Benedetti and Fabricio, {Aline S C} and Elisa Squarcina and Mauro Abbate and Ariela Benigni and Giuseppe Remuzzi and Marina Morigi",
year = "2012",
month = "7",
day = "20",
doi = "10.1089/scd.2011.0333",
language = "English",
volume = "21",
pages = "1911--1923",
journal = "Stem Cells and Development",
issn = "1547-3287",
publisher = "Mary Ann Liebert Inc.",
number = "11",

}

TY - JOUR

T1 - Human amniotic fluid stem cell preconditioning improves their regenerative potential

AU - Rota, Cinzia

AU - Imberti, Barbara

AU - Pozzobon, Michela

AU - Piccoli, Martina

AU - De Coppi, Paolo

AU - Atala, Anthony

AU - Gagliardini, Elena

AU - Xinaris, Christodoulos

AU - Benedetti, Valentina

AU - Fabricio, Aline S C

AU - Squarcina, Elisa

AU - Abbate, Mauro

AU - Benigni, Ariela

AU - Remuzzi, Giuseppe

AU - Morigi, Marina

PY - 2012/7/20

Y1 - 2012/7/20

N2 - Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning.

AB - Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning.

UR - http://www.scopus.com/inward/record.url?scp=84863936271&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863936271&partnerID=8YFLogxK

U2 - 10.1089/scd.2011.0333

DO - 10.1089/scd.2011.0333

M3 - Article

C2 - 22066606

AN - SCOPUS:84863936271

VL - 21

SP - 1911

EP - 1923

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 11

ER -