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Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis

Liu, Kehong ; Sakai, Kiyoshi ; Watanabe, Junna ; Dong, Jiao LU orcid ; Maruyama, Hiroshi ; Li, Xinheng and Hibi, Hideharu (2024) In Biochemical and Biophysical Research Communications 711.
Abstract

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine... (More)

Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cellular senescence, Conditioned medium, DNA damage response, Human mesenchymal stem cells, Postmenopausal osteoporosis
in
Biochemical and Biophysical Research Communications
volume
711
article number
149858
publisher
Elsevier
external identifiers
  • scopus:85190166840
  • pmid:38621345
ISSN
0006-291X
DOI
10.1016/j.bbrc.2024.149858
language
English
LU publication?
yes
id
23066c7a-ffcb-4a4c-87f7-06a948557960
date added to LUP
2024-04-24 14:07:30
date last changed
2024-06-19 19:15:38
@article{23066c7a-ffcb-4a4c-87f7-06a948557960,
  abstract     = {{<p>Systemic transplantation of mesenchymal stem cells (MSCs) and conditioned medium derived from MSCs have been reported to recover bone loss in animal models of osteoporosis; however, the underlying mechanisms remain unclear. We recently reported that extracellular vesicles released from human mesenchymal stem cells (hMSCs) prevent senescence of stem cells in bisphosphonate-related osteonecrosis of the jaw model. In this study, we aimed to compare the effects of conditioned medium (hMSCs-CM) from early and late passage hMSCs on cellular senescence and to verify the benefits of CM from early passage hMSCs in mitigating the progression of osteoporosis through the prevention of cellular senescence. We investigated the distinct endocrine effects of early (P5) and late (P17) passage hMSCs in vitro, as well as the preventive benefits of early passage hMSCs-CM in osteoporosis model triggered by ovariectomy. Our results indicate that long-term cultured hMSCs contributed to the progression of inflammatory transcriptional programs in P5 hMSCs, ultimately impairing their functionality and enhancing senescence-related characteristics. Conversely, early passage hMSCs reversed these alterations. Moreover, early passage hMSCs-CM infused intravenously in a postmenopausal osteoporosis mouse model suppressed bone degeneration and prevented osteoporosis by reducing ovariectomy-induced senescence in bone marrow MSCs and reducing the expression of senescence-associated secretory phenotype-related cytokines. Our findings highlight the high translational value of early passage hMSCs-CM in antiaging intervention and osteoporosis prevention.</p>}},
  author       = {{Liu, Kehong and Sakai, Kiyoshi and Watanabe, Junna and Dong, Jiao and Maruyama, Hiroshi and Li, Xinheng and Hibi, Hideharu}},
  issn         = {{0006-291X}},
  keywords     = {{Cellular senescence; Conditioned medium; DNA damage response; Human mesenchymal stem cells; Postmenopausal osteoporosis}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Conditioned medium of human mesenchymal stem cells affects stem cell senescence in osteoporosis}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2024.149858}},
  doi          = {{10.1016/j.bbrc.2024.149858}},
  volume       = {{711}},
  year         = {{2024}},
}