Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation
Mesenchymal stem cells (MSCs) are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report th...
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| Format: | Online |
| Language: | English |
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Elsevier
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375944/ |
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pubmed-43759442015-04-03 Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation Narcisi, Roberto Cleary, Mairéad A. Brama, Pieter A.J. Hoogduijn, Martin J. Tüysüz, Nesrin ten Berge, Derk van Osch, Gerjo J.V.M. Article Mesenchymal stem cells (MSCs) are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair. Elsevier 2015-02-26 /pmc/articles/PMC4375944/ /pubmed/25733021 http://dx.doi.org/10.1016/j.stemcr.2015.01.017 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Narcisi, Roberto Cleary, Mairéad A. Brama, Pieter A.J. Hoogduijn, Martin J. Tüysüz, Nesrin ten Berge, Derk van Osch, Gerjo J.V.M. |
| spellingShingle |
Narcisi, Roberto Cleary, Mairéad A. Brama, Pieter A.J. Hoogduijn, Martin J. Tüysüz, Nesrin ten Berge, Derk van Osch, Gerjo J.V.M. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation |
| author_facet |
Narcisi, Roberto Cleary, Mairéad A. Brama, Pieter A.J. Hoogduijn, Martin J. Tüysüz, Nesrin ten Berge, Derk van Osch, Gerjo J.V.M. |
| author_sort |
Narcisi, Roberto |
| title |
Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation |
| title_short |
Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation |
| title_full |
Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation |
| title_fullStr |
Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation |
| title_full_unstemmed |
Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation |
| title_sort |
long-term expansion, enhanced chondrogenic potential, and suppression of endochondral ossification of adult human mscs via wnt signaling modulation |
| description |
Mesenchymal stem cells (MSCs) are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair. |
| publisher |
Elsevier |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375944/ |
| _version_ |
1613204215251861504 |