Cargando…
Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo
Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796421/ https://www.ncbi.nlm.nih.gov/pubmed/33406724 http://dx.doi.org/10.3390/ma14010208 |
_version_ | 1783634678092136448 |
---|---|
author | Pham, Hai Thanh Ono, Mitsuaki Hara, Emilio Satoshi Nguyen, Ha Thi Thu Dang, Anh Tuan Do, Hang Thuy Komori, Taishi Tosa, Ikue Hazehara-Kunitomo, Yuri Yoshioka, Yuya Oida, Yasutaka Akiyama, Kentaro Kuboki, Takuo |
author_facet | Pham, Hai Thanh Ono, Mitsuaki Hara, Emilio Satoshi Nguyen, Ha Thi Thu Dang, Anh Tuan Do, Hang Thuy Komori, Taishi Tosa, Ikue Hazehara-Kunitomo, Yuri Yoshioka, Yuya Oida, Yasutaka Akiyama, Kentaro Kuboki, Takuo |
author_sort | Pham, Hai Thanh |
collection | PubMed |
description | Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss. |
format | Online Article Text |
id | pubmed-7796421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77964212021-01-10 Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo Pham, Hai Thanh Ono, Mitsuaki Hara, Emilio Satoshi Nguyen, Ha Thi Thu Dang, Anh Tuan Do, Hang Thuy Komori, Taishi Tosa, Ikue Hazehara-Kunitomo, Yuri Yoshioka, Yuya Oida, Yasutaka Akiyama, Kentaro Kuboki, Takuo Materials (Basel) Article Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss. MDPI 2021-01-04 /pmc/articles/PMC7796421/ /pubmed/33406724 http://dx.doi.org/10.3390/ma14010208 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pham, Hai Thanh Ono, Mitsuaki Hara, Emilio Satoshi Nguyen, Ha Thi Thu Dang, Anh Tuan Do, Hang Thuy Komori, Taishi Tosa, Ikue Hazehara-Kunitomo, Yuri Yoshioka, Yuya Oida, Yasutaka Akiyama, Kentaro Kuboki, Takuo Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo |
title | Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo |
title_full | Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo |
title_fullStr | Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo |
title_full_unstemmed | Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo |
title_short | Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo |
title_sort | tryptophan and kynurenine enhances the stemness and osteogenic differentiation of bone marrow-derived mesenchymal stromal cells in vitro and in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796421/ https://www.ncbi.nlm.nih.gov/pubmed/33406724 http://dx.doi.org/10.3390/ma14010208 |
work_keys_str_mv | AT phamhaithanh tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT onomitsuaki tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT haraemiliosatoshi tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT nguyenhathithu tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT danganhtuan tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT dohangthuy tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT komoritaishi tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT tosaikue tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT hazeharakunitomoyuri tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT yoshiokayuya tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT oidayasutaka tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT akiyamakentaro tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo AT kubokitakuo tryptophanandkynurenineenhancesthestemnessandosteogenicdifferentiationofbonemarrowderivedmesenchymalstromalcellsinvitroandinvivo |