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Int J Mol Sci ; 21(19)2020 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-33036225

RESUMEN

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-ß1 blocker with anti-fibrotic properties) could decrease TGF-ß1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-ß1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-ß1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (p = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (p = 0.03).


Asunto(s)
Fibroblastos/efectos de los fármacos , Fibrosis/prevención & control , Losartán/farmacología , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Cicatrización de Heridas/efectos de los fármacos , Administración Oral , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Células de la Médula Ósea , Transición Epitelial-Mesenquimal , Fibroblastos/metabolismo , Fibrosis/metabolismo , Antígenos Comunes de Leucocito/análisis , Losartán/administración & dosificación , Losartán/uso terapéutico , Plasma Rico en Plaquetas , Conejos , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo
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