High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cells
Abstract Chronic hyperglycemia is recognized as an important contributor to chronic inflammation, oxidative stress, and organ dysfunction that causes serious complications in diabetes and aging. This study investigates the effects of elevated glucose levels on human placenta-derived mesenchymal stem...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-06454-3 |
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| author | Supawadee Duangprom Pakpoom Kheolamai Chairat Tantrawatpan Sirikul Manochantr |
| author_facet | Supawadee Duangprom Pakpoom Kheolamai Chairat Tantrawatpan Sirikul Manochantr |
| author_sort | Supawadee Duangprom |
| collection | DOAJ |
| description | Abstract Chronic hyperglycemia is recognized as an important contributor to chronic inflammation, oxidative stress, and organ dysfunction that causes serious complications in diabetes and aging. This study investigates the effects of elevated glucose levels on human placenta-derived mesenchymal stem cells (hP-MSCs), especially since these cells hold a promise for tissue engineering and regenerative medicine due to their multipotency and self-renewal capabilities. hP-MSCs were treated with 10–40 mM D-glucose to study the effects of high glucose on hP-MSCs functions. hP-MSCs viability and proliferation were determined by using thiazolyl blue tetrazolium bromide (MTT), cell cycle analysis, and senescence assays. The migration and osteogenic differentiation capacity were also determined by migration assay, alkaline phosphatase (ALP) activity assay, and Alizarin Red S staining. Quantitative real-time RT-PCR, Western blot, and Nanostring® nCounter assay were performed to study the effect of high glucose on the expression levels of genes involved in various aspects of hP-MSCs functions. The results demonstrated that high glucose significantly inhibited proliferation and cell cycle progression of hP-MSCs at the G1/S phase and induced replicative senescence in hP-MSCs possibly by decreasing the expression of proliferation-promoting genes, CCND1 and LMNB1, and increasing the expression of several senescence-associated proteins, p16, p21, and p53. Furthermore, high glucose also inhibited the migration and osteogenic differentiation of hP-MSCs, possibly by suppressing the expression of SDF1, CXCR4, RUNX2, OSX, OCN, and COL1A. The additional Nanostring analysis also showed that high glucose significantly affects multiple genes involved in inflammation, DNA repair, autophagy, and oxidative stress response in hP-MSCs. This study provides significant insights into the wide-ranging effects of high glucose on the expression of the hP-MSCs genes that affect various aspects of its function, including proliferation, viability, senescence, oxidative stress response, and DNA repair, highlighting its implications for regenerative medicine in the context of diabetes and metabolic disorders. |
| format | Article |
| id | doaj-art-b4d49f7de92949a3b50c801ce8966f2f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b4d49f7de92949a3b50c801ce8966f2f2025-08-20T03:37:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-06454-3High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cellsSupawadee Duangprom0Pakpoom Kheolamai1Chairat Tantrawatpan2Sirikul Manochantr3Division of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityDivision of Cell Biology, Department of Preclinical Sciences, Faculty of Medicine, Thammasat UniversityAbstract Chronic hyperglycemia is recognized as an important contributor to chronic inflammation, oxidative stress, and organ dysfunction that causes serious complications in diabetes and aging. This study investigates the effects of elevated glucose levels on human placenta-derived mesenchymal stem cells (hP-MSCs), especially since these cells hold a promise for tissue engineering and regenerative medicine due to their multipotency and self-renewal capabilities. hP-MSCs were treated with 10–40 mM D-glucose to study the effects of high glucose on hP-MSCs functions. hP-MSCs viability and proliferation were determined by using thiazolyl blue tetrazolium bromide (MTT), cell cycle analysis, and senescence assays. The migration and osteogenic differentiation capacity were also determined by migration assay, alkaline phosphatase (ALP) activity assay, and Alizarin Red S staining. Quantitative real-time RT-PCR, Western blot, and Nanostring® nCounter assay were performed to study the effect of high glucose on the expression levels of genes involved in various aspects of hP-MSCs functions. The results demonstrated that high glucose significantly inhibited proliferation and cell cycle progression of hP-MSCs at the G1/S phase and induced replicative senescence in hP-MSCs possibly by decreasing the expression of proliferation-promoting genes, CCND1 and LMNB1, and increasing the expression of several senescence-associated proteins, p16, p21, and p53. Furthermore, high glucose also inhibited the migration and osteogenic differentiation of hP-MSCs, possibly by suppressing the expression of SDF1, CXCR4, RUNX2, OSX, OCN, and COL1A. The additional Nanostring analysis also showed that high glucose significantly affects multiple genes involved in inflammation, DNA repair, autophagy, and oxidative stress response in hP-MSCs. This study provides significant insights into the wide-ranging effects of high glucose on the expression of the hP-MSCs genes that affect various aspects of its function, including proliferation, viability, senescence, oxidative stress response, and DNA repair, highlighting its implications for regenerative medicine in the context of diabetes and metabolic disorders.https://doi.org/10.1038/s41598-025-06454-3Mesenchymal stem cellsDiabetesOsteogenic differentiationPlacentaSenescence |
| spellingShingle | Supawadee Duangprom Pakpoom Kheolamai Chairat Tantrawatpan Sirikul Manochantr High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cells Scientific Reports Mesenchymal stem cells Diabetes Osteogenic differentiation Placenta Senescence |
| title | High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cells |
| title_full | High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cells |
| title_fullStr | High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cells |
| title_full_unstemmed | High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cells |
| title_short | High glucose inhibits proliferation, migration, and osteogenic differentiation of human placenta-derived mesenchymal stem cells |
| title_sort | high glucose inhibits proliferation migration and osteogenic differentiation of human placenta derived mesenchymal stem cells |
| topic | Mesenchymal stem cells Diabetes Osteogenic differentiation Placenta Senescence |
| url | https://doi.org/10.1038/s41598-025-06454-3 |
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