Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we comp...

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Main Authors: Hideki Agata, Yoshinori Sumita, Tatsuro Hidaka, Mayumi Iwatake, Hideaki Kagami, Izumi Asahina
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/4214281
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author Hideki Agata
Yoshinori Sumita
Tatsuro Hidaka
Mayumi Iwatake
Hideaki Kagami
Izumi Asahina
author_facet Hideki Agata
Yoshinori Sumita
Tatsuro Hidaka
Mayumi Iwatake
Hideaki Kagami
Izumi Asahina
author_sort Hideki Agata
collection DOAJ
description Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis.
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spelling doaj-art-cb22e8401fce40af8193568ad29a0b332025-02-03T05:58:43ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/42142814214281Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating OsteoporosisHideki Agata0Yoshinori Sumita1Tatsuro Hidaka2Mayumi Iwatake3Hideaki Kagami4Izumi Asahina5Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDivision of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanBasic and Translational Research Center for Hard Tissue Disease, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDivision of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, JapanDepartment of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanMesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis.http://dx.doi.org/10.1155/2019/4214281
spellingShingle Hideki Agata
Yoshinori Sumita
Tatsuro Hidaka
Mayumi Iwatake
Hideaki Kagami
Izumi Asahina
Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis
Stem Cells International
title Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis
title_full Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis
title_fullStr Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis
title_full_unstemmed Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis
title_short Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis
title_sort intra bone marrow administration of mesenchymal stem stromal cells is a promising approach for treating osteoporosis
url http://dx.doi.org/10.1155/2019/4214281
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