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Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification
Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Acco...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533314/ https://www.ncbi.nlm.nih.gov/pubmed/34680525 http://dx.doi.org/10.3390/biomedicines9101408 |
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author | Horikoshi, Susumu Kajiya, Mikihito Motoike, Souta Yoshino, Mai Morimoto, Shin Yoshii, Hiroki Ogawa, Tomoya Sone, Hisakatsu Iwata, Tomoyuki Ouhara, Kazuhisa Matsuda, Shinji Mizuno, Noriyoshi Kurihara, Hidemi |
author_facet | Horikoshi, Susumu Kajiya, Mikihito Motoike, Souta Yoshino, Mai Morimoto, Shin Yoshii, Hiroki Ogawa, Tomoya Sone, Hisakatsu Iwata, Tomoyuki Ouhara, Kazuhisa Matsuda, Shinji Mizuno, Noriyoshi Kurihara, Hidemi |
author_sort | Horikoshi, Susumu |
collection | PubMed |
description | Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification. |
format | Online Article Text |
id | pubmed-8533314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85333142021-10-23 Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification Horikoshi, Susumu Kajiya, Mikihito Motoike, Souta Yoshino, Mai Morimoto, Shin Yoshii, Hiroki Ogawa, Tomoya Sone, Hisakatsu Iwata, Tomoyuki Ouhara, Kazuhisa Matsuda, Shinji Mizuno, Noriyoshi Kurihara, Hidemi Biomedicines Article Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification. MDPI 2021-10-07 /pmc/articles/PMC8533314/ /pubmed/34680525 http://dx.doi.org/10.3390/biomedicines9101408 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Horikoshi, Susumu Kajiya, Mikihito Motoike, Souta Yoshino, Mai Morimoto, Shin Yoshii, Hiroki Ogawa, Tomoya Sone, Hisakatsu Iwata, Tomoyuki Ouhara, Kazuhisa Matsuda, Shinji Mizuno, Noriyoshi Kurihara, Hidemi Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification |
title | Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification |
title_full | Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification |
title_fullStr | Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification |
title_full_unstemmed | Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification |
title_short | Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification |
title_sort | clumps of mesenchymal stem cells/extracellular matrix complexes generated with xeno-free chondro-inductive medium induce bone regeneration via endochondral ossification |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533314/ https://www.ncbi.nlm.nih.gov/pubmed/34680525 http://dx.doi.org/10.3390/biomedicines9101408 |
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