title: Mesenchymal stem cell therapy prevents interstitial fibrosis and tubular atrophy in a rat kidney allograft model.
abstract: In solid organ transplantation, mesenchymal stem cell (MSC) therapy is strongly emerging among other cell therapies due to the positive results obtained in vitro and in vivo as an immunomodulatory agent and their potential regenerative role. We aimed at testing whether a single dose of MSCs, injected at 11 weeks after kidney transplantation for the prevention of chronic mechanisms, enhanced regeneration and provided protection against the inflammatory and fibrotic processes that finally lead to the characteristic features of chronic allograft nephropathy (CAN). Either bone marrow mononuclear cells (BMCs) injection or no-therapy (NT) were used as control treatments. A rat kidney transplantation model of CAN with 2.5 h of cold ischemia was used, and functional, histological, and molecular parameters were assessed at 12 and 24 weeks after transplantation. MSC and BMC cell therapy preserves renal function at 24 weeks and abrogates proteinuria, which is typical of this model (NT24w: 68.9 ± 26.5 mg/24 h, MSC24w: 16.6 ± 2.3 mg/24 h, BMC24w: 24.1 ± 5.3 mg/24 h, P<0.03). Only MSC-treated animals showed a reduction in interstitial fibrosis and tubular atrophy (NT24w: 2.3 ± 0.29, MSC24w: 0.4 ± 0.2, P<0.03), less T cells (NT: 39.6 ± 9.5, MSC: 8.1 ± 0.9, P<0.03) and macrophages (NT: 20.9 ± 4.7, MSC: 5.9 ± 1.7, P<0.05) infiltrating the parenchyma and lowered expression of inflammatory cytokines while increasing the expression of anti-inflammatory factors. MSCs appear to serve as a protection from injury development rather than regenerate the damaged tissue, as no differences were observed in Ki67 expression, and kidney injury molecule-1, Clusterin, NGAL, and hepatocyte growth factor expression were only up-regulated in nontreated animals. Considering the results, a single delayed MSC injection is effective for the long-term protection of kidney allografts.
authors.affiliation: Experimental Renal Transplantation, Laboratory of Experimental Nephrology, Bellvitge Biomedical Research Institute (IDIBELL)- Universitat de Barcelona (UB), Barcelona, Spain. mfranquesa@ub.edu
authors.forename: Marcella
authors.initials: M
authors.lastname: Franquesa
authors.forename: Esther
authors.initials: E
authors.lastname: Herrero
authors.forename: Joan
authors.initials: J
authors.lastname: Torras
authors.forename: Elia
authors.initials: E
authors.lastname: Ripoll
authors.forename: Maria
authors.initials: M
authors.lastname: Flaquer
authors.forename: Montse
authors.initials: M
authors.lastname: Gomà
authors.forename: Nuria
authors.initials: N
authors.lastname: Lloberas
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Immaculada
authors.initials: I
authors.lastname: Herrero-Fresneda
mesh_terms: D000818:Animals; D001284:Atrophy / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D005355:Fibrosis; D005805:Genes, MHC Class I; D007150:Immunohistochemistry; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D007668:Kidney / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011507:Proteinuria / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012038:Regeneration; D051437:Renal Insufficiency / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D014184:Transplantation, Homologous
chemical_list: D018836:Inflammation Mediators; D007378:Interleukins