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Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence

Dong, Jiao LU orcid ; Sakai, Kiyoshi ; Koma, Yoshiro ; Watanabe, Junna ; Liu, Kehong ; Maruyama, Hiroshi ; Sakaguchi, Kohei and Hibi, Hideharu (2021) In Biochemical and Biophysical Research Communications 575. p.28-35
Abstract

Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular... (More)

Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy + PBS group showed a high senescence-associated-β-galactosidase-positive cell number and upregulated senescence-related gene (p16INK4a, p19Arf, p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-κB, and TGF-β) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cellular senescence, DNA damage Response, Human dental pulp stem cell, Oxidative stress, Salivary gland hypofunction, Small extracellular vesicle
in
Biochemical and Biophysical Research Communications
volume
575
pages
8 pages
publisher
Elsevier
external identifiers
  • scopus:85113452863
  • pmid:34454177
ISSN
0006-291X
DOI
10.1016/j.bbrc.2021.08.046
language
English
LU publication?
yes
id
25f3bf21-ef87-4bc3-a15b-dfa2db0a5224
date added to LUP
2021-09-17 13:24:53
date last changed
2024-06-15 16:30:37
@article{25f3bf21-ef87-4bc3-a15b-dfa2db0a5224,
  abstract     = {{<p>Small extracellular vesicles (sEV) facilitate signaling molecule transfer among cells. We examined the therapeutic efficacy of human dental pulp stem cell-derived sEV (hDPSC-sEV) against cellular senescence in an irradiated-submandibular gland mouse model. Seven-week-old mice were exposed to 25 Gy radiation and randomly assigned to control, phosphate-buffered saline (PBS), or hDPSC-sEV groups. At 18 days post-irradiation, saliva production was measured; histological and reverse transcription-quantitative PCR analyses of the submandibular glands were performed. The salivary flow rate did not differ significantly between the PBS and hDPSC-sEV groups. AQP5-expressing acinar cell numbers and AQP5 expression levels in the submandibular glands were higher in the hDPSC-sEV group than in the other groups. Furthermore, compared with non-irradiated mice, mice in the 25 Gy + PBS group showed a high senescence-associated-β-galactosidase-positive cell number and upregulated senescence-related gene (p16<sup>INK4a</sup>, p19<sup>Arf</sup>, p21) and senescence-associated secretory phenotypic factor (MMP3, IL-6, PAI-1, NF-κB, and TGF-β) expression, all of which were downregulated in the hDPSC-sEV group. Superoxide dismutase levels were lower in the PBS group than in the hDPSC-sEV group. In summary, hDPSC-sEV reduced inflammatory cytokine and senescence-related gene expression and reversed oxidative stress in submandibular cells, thereby preventing irradiation-induced cellular senescence. Based on these results, we hope to contribute to the development of innovative treatment methods for salivary gland dysfunction that develops after radiotherapy for head and neck cancer.</p>}},
  author       = {{Dong, Jiao and Sakai, Kiyoshi and Koma, Yoshiro and Watanabe, Junna and Liu, Kehong and Maruyama, Hiroshi and Sakaguchi, Kohei and Hibi, Hideharu}},
  issn         = {{0006-291X}},
  keywords     = {{Cellular senescence; DNA damage Response; Human dental pulp stem cell; Oxidative stress; Salivary gland hypofunction; Small extracellular vesicle}},
  language     = {{eng}},
  pages        = {{28--35}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Dental pulp stem cell-derived small extracellular vesicle in irradiation-induced senescence}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2021.08.046}},
  doi          = {{10.1016/j.bbrc.2021.08.046}},
  volume       = {{575}},
  year         = {{2021}},
}