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Mesenchymal stem cell therapy promotes renal repair by limiting glomerular podocyte and progenitor cell dysfunction in adriamycin-induced nephropathy.
Zoja, Carla; Garcia, Pablo Bautista; Rota, Cinzia; Conti, Sara; Gagliardini, Elena; Corna, Daniela; Zanchi, Cristina; Bigini, Paolo; Benigni, Ariela; Remuzzi, Giuseppe; Morigi, Marina.
Afiliación
  • Zoja C; Mario Negri Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Km Rosso, Via Stezzano, 87-24126 Bergamo, Italy. carlamaria.zoja@marionegri.it
Am J Physiol Renal Physiol ; 303(9): F1370-81, 2012 Nov 01.
Article en En | MEDLINE | ID: mdl-22952284
We previously reported that in a model of spontaneously progressive glomerular injury with early podocyte loss, abnormal migration, and proliferation of glomerular parietal epithelial progenitor cells contributed to the formation of synechiae and crescentic lesions. Here we first investigated whether a similar sequence of events could be extended to rats with adriamycin (ADR)-induced nephropathy. As a second aim, the regenerative potential of therapy with bone marrow-derived mesenchymal stem cells (MSCs) on glomerular resident cells was evaluated. In ADR-treated rats, decrease of WT1(+) podocyte number due to apoptosis was associated with reduced glomerular expression of nephrin and CD2AP. As a consequence of podocyte injury, glomerular adhesions of the capillary tuft to the Bowman's capsule were observed, followed by crescent-like lesions and glomerulosclerosis. Cellular components of synechiae were either NCAM(+) parietal progenitor cells or nestin(+) podocytes. In ADR rats, repeated injections of MSCs limited podocyte loss and apoptosis and partially preserved nephrin and CD2AP. MSCs attenuated the formation of glomerular podocyte-parietal epithelial cell bridges and normalized the distribution of NCAM(+) progenitor cells along the Bowman's capsule, thereby reducing glomerulosclerosis. Finding that MSCs increased glomerular VEGF expression and limited microvascular rarefaction may explain the prosurvival effect by stem cell therapy. MSCs also displayed anti-inflammatory activity. Coculture of MSCs with ADR-damaged podocytes showed a functional role of stem cell-derived VEGF on prosurvival pathways. These data suggest that MSCs by virtue of their tropism for damaged kidney and ability to provide a local prosurvival environment may represent a useful strategy to preserve podocyte viability and reduce glomerular inflammation and sclerosis.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Células Madre / Trasplante de Células Madre Mesenquimatosas / Podocitos / Riñón / Enfermedades Renales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Células Madre / Trasplante de Células Madre Mesenquimatosas / Podocitos / Riñón / Enfermedades Renales Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Renal Physiol Asunto de la revista: FISIOLOGIA / NEFROLOGIA Año: 2012 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos