Bone marrow mononuclear cells attenuate interstitial fibrosis and stimulate the repair of tubular epithelial cells after unilateral ureteral obstruction.
The growing number of patients suffering from chronic renal disease is a challenge for the development of innovative therapies. Benefits of cell therapy in acute renal diseases in animal models have been reported but seldom for chronic lesions. We present evidence for the improvement of renal morphology in a model of tubulointerstitial fibrosis. Wistar rats were submitted to unilateral ureteral obstruction (UUO), treated with bone-marrow mononuclear cells (UUO+BMMC) infused via the cava vein, and killed on day 14. Labeled BMMC were seen in renal tissue after 7 days in the group UUO+BMMC. UUO+BMMC also showed a reduction in ED1(+) cells and tubular apoptotic cells together with enhanced tubular proliferation. Myofibroblasts were also reduced after BMMC which is consistent with a decrease in collagen deposition (picro Sirius staining) and RT-PCR data showing lower levels of procollagen-I mRNA. Simultaneously, nestin+ cells increased in the interstitium and decreased in the tubules. Double stained nestin(+)/alpha-SMA(+) cells were present only in the interstitium, and their levels did not change after BMMC infusion. These data indicate a renoprotective effect of BMMC through increased tubular cell regeneration, inhibition of tubular cell apoptosis and partially blocking of the inflammatory and fibrotic events that occur after unilateral ureteral obstruction.
Barreira
André L
AL
Hospital Universitário "Clementino Fraga Filho", Universidade Federal do Rio de Janeiro, Brazil.
Takiya
Christina M
CM
Castiglione
Raquel C
RC
Maron-Gutierrez
Tatiana
T
Barbosa
Carolina M L
CM
Ornellas
Débora S
DS
Verdoorn
Karine S
KS
Pascarelli
Bernardo M
BM
Borojevic
Radovan
R
Einicker-Lamas
Marcelo
M
Leite
Maurilo
M
Morales
Marcelo M
MM
Vieyra
Adalberto
A
D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D005355:Fibrosis; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014517:Ureteral Obstruction / Q000473:pathology / Q000628:therapy*
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D011347:Procollagen