Background. Mesenchymal stem cells (MSC) may be of value in
regeneration of renal tissue after damage, however lack of biological knowledge and
variability of results in animal models limit their utilization.
Methods. We studied the effects of MSC on podocytes ‘in vitro’ and ‘in vivo’
utilizing adriamycin (ADR) as a model of renal toxicity. The ‘in vivo’ experimental
approach was carried out in male Sprague Dawley rats (overall 60 animals) treated
with different ADR schemes to induce acute and chronic nephrosis. MSC were
given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days
after ADR. Homing was assessed with PKH26-MSC.
Results. MSC rescued podocytes from apoptosis induced by ADR ‘in vitro’. The
maximal effect (80% rescue) was obtained with MSC/Podocytes co-culture ratio of
1:1 for 72 hours. All rats treated with ADR developed nephrosis. In no case MSC
modified the clinical parameters (i.e. proteinuria, serum creatinine, lipids) but
protected the kidney from severe glomerulosclerosis when given concomitantly to
ADR. Rats given MSC 60 days after ADR developed the same severe renal damage.
Only few MSC were found in renal tubule-interstitial areas after 1-24 hours from
injection and no MSC was detected in glomeruli.
Conclusions. MSC reduced apoptosis of podocytes treated with ADR ‘in vitro’.
Early and repeated MSC infusion blunted glomerular damage in chronic ADR
nephropathy. MSC did not modify proteinuria and progression to renal failure, that
implies lack of regenerative potential in this model.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:1085 |
| Date | 04 April 2008 |
| Creators | Magnasco, Alberto <1964> |
| Contributors | Gusmano, Rosanna |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | Italian |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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