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.

Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels

“…[26][27][28][29][30] Alternatively, broad potential for differentiation and high proliferation rates make AFSC well suited for use in regenerative medicine therapies such as engineered skeletal/cardiac muscles, tendons, heart valves, and blood vessels. 11,17,[31][32][33][34][35] This study confirms our previous work on the capacity for VEGF-mediated differentiation of c-kit + AFSC into endothelial-like cells, 14 as well as illustrates the vasculogenic and perivasculogenic potential of AFSC within a threedimensional fibrin/PEG scaffold in vitro.…”

Functional Human Podocytes Generated in Organoids from Amniotic Fluid Stem Cells

“…38 CD117-positive AFSCs were grown in modified a-MEM (Gibco BRL, Gaithersburg, MD) containing 15% embryonic stem cells FBS (ES-FBS, Gibco, Invitrogen Corporation, Grand Island,NY), 1% L-glutamine (Invitrogen Corporation, Carlsbad, CA), and 1% penicillin/streptomycin (Invitrogen), supplemented with 18% Chang B and 2% Chang C (Irvine Scientific, Santa Ana, CA), as previously described. 39,40 AFSCs were genetically modified to express GDNF by infection with the adenovirus AxCAh-GDNF, which was generated as previously described. 15 The cells were infected with 250 moi of AxCAh-GDNF in medium without antibiotics and serum for 3 hours.…”

Comparative study of immune regulatory properties of stem cells derived from different tissues

“…Each SC type was characterized in terms of phenotype and differentiation potential [22,44,50,53,54] following International Society for Cellular Therapy (ISCT)-minimal criteria [55].…”