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.
authors: Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.
authors: Cinzia
authors: C
authors: Rota
authors: Barbara
authors: B
authors: Imberti
authors: Michela
authors: M
authors: Pozzobon
authors: Martina
authors: M
authors: Piccoli
authors: Paolo
authors: P
authors: De Coppi
authors: Anthony
authors: A
authors: Atala
authors: Elena
authors: E
authors: Gagliardini
authors: Christodoulos
authors: C
authors: Xinaris
authors: Valentina
authors: V
authors: Benedetti
authors: Aline S C
authors: AS
authors: Fabricio
authors: Elisa
authors: E
authors: Squarcina
authors: Mauro
authors: M
authors: Abbate
authors: Ariela
authors: A
authors: Benigni
authors: Giuseppe
authors: G
authors: Remuzzi
authors: Marina
authors: M
authors: Morigi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002945:Cisplatin / Q000009:adverse effects*; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D017077:Culture Media, Conditioned; D051100:Glial Cell Line-Derived Neurotrophic Factor; D002945:Cisplatin