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Title: Mesenchymal Stem Cell Therapy Prevents Interstitial Fibrosis and Tubular Atrophy in a Rat Kidney Allograft Model
Author: Franquesa, Marcella
Herrero, Esther
Torras Ambròs, Joan
Ripoll Llagostera, Èlia
Flaquer, Maria
Gomà, Montse
Lloberas Blanch, Núria
Anegon, Ignacio
Cruzado, Josep Ma.
Grinyó Boira, Josep M.
Herrero Fresneda, Immaculada
Keywords: Trasplantament d'òrgans
Malalties del ronyó
Transplantation of organs, tissues, etc.
Kidney diseases
Issue Date: 1-Nov-2012
Publisher: Mary Ann Liebert
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 +/- 26.5mg/24 h, MSC24w: 16.6 +/- 2.3mg/24 h, BMC24w: 24.1 +/- 5.3mg/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.
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It is part of: Stem Cells and Development, 2012, vol. 21, num. 17, p. 3125-3135
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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