Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats

Medication-related osteonecrosis of the jaw (MRONJ) is defined as the exposed necrotic bone involving the maxillofacial structures in bisphosphonate treated patients, and the pathophysiology of this disease remains unclear. The aim of this study was to assess the effects of the allogeneic transplant...

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Main Authors: Francisco Javier Rodríguez-Lozano, Ricardo Oñate-Sánchez, Mar Gonzálvez-García, Marta Vallés-Bergadá, Carlos M. Martínez, Beatriz Revilla-Nuin, Julia Guerrero-Gironés, Jose M. Moraleda, David García-Bernal
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:Journal of Clinical Medicine
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Online Access:https://www.mdpi.com/2077-0383/9/6/1649
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author Francisco Javier Rodríguez-Lozano
Ricardo Oñate-Sánchez
Mar Gonzálvez-García
Marta Vallés-Bergadá
Carlos M. Martínez
Beatriz Revilla-Nuin
Julia Guerrero-Gironés
Jose M. Moraleda
David García-Bernal
author_facet Francisco Javier Rodríguez-Lozano
Ricardo Oñate-Sánchez
Mar Gonzálvez-García
Marta Vallés-Bergadá
Carlos M. Martínez
Beatriz Revilla-Nuin
Julia Guerrero-Gironés
Jose M. Moraleda
David García-Bernal
author_sort Francisco Javier Rodríguez-Lozano
collection DOAJ
description Medication-related osteonecrosis of the jaw (MRONJ) is defined as the exposed necrotic bone involving the maxillofacial structures in bisphosphonate treated patients, and the pathophysiology of this disease remains unclear. The aim of this study was to assess the effects of the allogeneic transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a model of Wistar mice with induced MRONJ disease. BM-MSCs from five male Wistar rats were characterized and cultured on β-tricalcium phosphate (β-TCP) granules. Thirty female Wistar rats were injected intraperitoneally with zoledronic acid and afterwards upper jaw molars were extracted. The animals were randomized to receive: Group 1: 1 × 10<sup>6</sup> BM-MSCs/β-TCP construct in the alveolar socket; and Group 2: Saline solution/β-TCP construct. A clinical and histological analysis was performed. Nested polymerase chain reaction (PCR) was assessed to verify the presence of transplanted male rat cells in the female recipient jaws. Clinical and histological findings evidenced that none of the animals in Group 1 exhibited uncovered sockets or bone exposure associated to MRONJ, whereas we detected 33% of MRONJ cases in Group 2. In addition, male rat cells were detected in the maxillae site four weeks after transplantation in the BM-MSCs-group. Allogeneic BM-MSCs in extractions sites ameliorates MRONJ incidence in zoledronic acid-treated rats compared to non-MSC treatments.
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spelling doaj.art-f80f795678d14e2cb13f8dfeaa14290a2023-11-20T02:22:05ZengMDPI AGJournal of Clinical Medicine2077-03832020-05-0196164910.3390/jcm9061649Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated RatsFrancisco Javier Rodríguez-Lozano0Ricardo Oñate-Sánchez1Mar Gonzálvez-García2Marta Vallés-Bergadá3Carlos M. Martínez4Beatriz Revilla-Nuin5Julia Guerrero-Gironés6Jose M. Moraleda7David García-Bernal8Special Care in Dentistry-Gerodontology Unit, Department of Dermatology, Stomatology, Radiology and Physical Medicine, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, SpainSpecial Care in Dentistry-Gerodontology Unit, Department of Dermatology, Stomatology, Radiology and Physical Medicine, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, SpainFaculty of Health Sciences, Catholic University of Murcia, 30107 Murcia, SpainDental and Maxillofacial Surgery Unit, Quirónsalud Torrevieja, Partida de la Loma, s/n, 03184 Torrevieja, Alicante, SpainExperimental Pathology Unit, Biomedical Research Institute of Murcia-Arrixaca, IMIB-Arrixaca, 30120 Murcia, SpainGenomics Unit, Biomedical Research Institute of Murcia-Arrixaca, IMIB-Arrixaca, 30120 Murcia, SpainSpecial Care in Dentistry-Gerodontology Unit, Department of Dermatology, Stomatology, Radiology and Physical Medicine, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, SpainResearch Group Cellular Therapy and Hematopoietic Transplant, Biomedical Research Institute, Virgen de la Arrixaca Clinical University Hospital, IMIB-Arrixaca, University of Murcia, Avenida Buenavista s/n, 30120 Murcia, SpainResearch Group Cellular Therapy and Hematopoietic Transplant, Biomedical Research Institute, Virgen de la Arrixaca Clinical University Hospital, IMIB-Arrixaca, University of Murcia, Avenida Buenavista s/n, 30120 Murcia, SpainMedication-related osteonecrosis of the jaw (MRONJ) is defined as the exposed necrotic bone involving the maxillofacial structures in bisphosphonate treated patients, and the pathophysiology of this disease remains unclear. The aim of this study was to assess the effects of the allogeneic transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) in a model of Wistar mice with induced MRONJ disease. BM-MSCs from five male Wistar rats were characterized and cultured on β-tricalcium phosphate (β-TCP) granules. Thirty female Wistar rats were injected intraperitoneally with zoledronic acid and afterwards upper jaw molars were extracted. The animals were randomized to receive: Group 1: 1 × 10<sup>6</sup> BM-MSCs/β-TCP construct in the alveolar socket; and Group 2: Saline solution/β-TCP construct. A clinical and histological analysis was performed. Nested polymerase chain reaction (PCR) was assessed to verify the presence of transplanted male rat cells in the female recipient jaws. Clinical and histological findings evidenced that none of the animals in Group 1 exhibited uncovered sockets or bone exposure associated to MRONJ, whereas we detected 33% of MRONJ cases in Group 2. In addition, male rat cells were detected in the maxillae site four weeks after transplantation in the BM-MSCs-group. Allogeneic BM-MSCs in extractions sites ameliorates MRONJ incidence in zoledronic acid-treated rats compared to non-MSC treatments.https://www.mdpi.com/2077-0383/9/6/1649bone marrow mesenchymal stem cellszoledronic acidosteonecrosisjawMRONJ
spellingShingle Francisco Javier Rodríguez-Lozano
Ricardo Oñate-Sánchez
Mar Gonzálvez-García
Marta Vallés-Bergadá
Carlos M. Martínez
Beatriz Revilla-Nuin
Julia Guerrero-Gironés
Jose M. Moraleda
David García-Bernal
Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats
Journal of Clinical Medicine
bone marrow mesenchymal stem cells
zoledronic acid
osteonecrosis
jaw
MRONJ
title Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats
title_full Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats
title_fullStr Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats
title_full_unstemmed Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats
title_short Allogeneic Bone Marrow Mesenchymal Stem Cell Transplantation in Tooth Extractions Sites Ameliorates the Incidence of Osteonecrotic Jaw-Like Lesions in Zoledronic Acid-Treated Rats
title_sort allogeneic bone marrow mesenchymal stem cell transplantation in tooth extractions sites ameliorates the incidence of osteonecrotic jaw like lesions in zoledronic acid treated rats
topic bone marrow mesenchymal stem cells
zoledronic acid
osteonecrosis
jaw
MRONJ
url https://www.mdpi.com/2077-0383/9/6/1649
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