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Effect of acidosis on adipose-derived stem cell impairment and gene expression

Huang, Kun ; Wang, Qinqin ; Qu, Huilong ; Hu, Xinyu ; Niu, Wenhao ; Hultgårdh-Nilsson, Anna LU ; Nilsson, Jan LU ; Liang, Chun LU and Chen, Yihong LU (2024) In Regenerative Therapy 25. p.331-343
Abstract

Based on disappointing results of stem cell-based application in clinical trials for patients with critical limb ischemia, we hypothesized that the acidic environment might be the key factor limiting cell survival and function. In the present study, we used microdialysis to determine presence of acidosis and metabolic imbalance in critical ischemia. Moreover, we explored the effect of extracellular acidosis on adipose-derived stem cells (ADSCs) at molecular and transcriptional level. Our data demonstrate that low pH negatively regulates cell proliferation and survival, also, it results in cell cycle arrest, mitochondrial dynamics disorder, DNA damage as well as the impairment of proangiogenic function in a pH-dependent manner. Further... (More)

Based on disappointing results of stem cell-based application in clinical trials for patients with critical limb ischemia, we hypothesized that the acidic environment might be the key factor limiting cell survival and function. In the present study, we used microdialysis to determine presence of acidosis and metabolic imbalance in critical ischemia. Moreover, we explored the effect of extracellular acidosis on adipose-derived stem cells (ADSCs) at molecular and transcriptional level. Our data demonstrate that low pH negatively regulates cell proliferation and survival, also, it results in cell cycle arrest, mitochondrial dynamics disorder, DNA damage as well as the impairment of proangiogenic function in a pH-dependent manner. Further transcriptome profiling identified the pivotal signaling pathways and hub genes in response to acidosis. Collectively, these findings provide strong evidences for a critical role of acidosis in ADSCs impairment with ischemic condition and suggest treatments focus on tissue pH balance and acidosis-mediated hub genes may have therapeutic potential in stem cell-based application.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acidosis, Adipose-derived stem cells, Angiogenesis, Ischemia, pH regulation
in
Regenerative Therapy
volume
25
pages
13 pages
publisher
Japanese Society of Regenerative Medicine
external identifiers
  • pmid:38333090
  • scopus:85183965088
ISSN
2352-3204
DOI
10.1016/j.reth.2024.01.010
language
English
LU publication?
yes
id
e4952622-4337-4661-9286-b3c8dcc38777
date added to LUP
2024-03-06 13:29:37
date last changed
2024-04-18 14:19:18
@article{e4952622-4337-4661-9286-b3c8dcc38777,
  abstract     = {{<p>Based on disappointing results of stem cell-based application in clinical trials for patients with critical limb ischemia, we hypothesized that the acidic environment might be the key factor limiting cell survival and function. In the present study, we used microdialysis to determine presence of acidosis and metabolic imbalance in critical ischemia. Moreover, we explored the effect of extracellular acidosis on adipose-derived stem cells (ADSCs) at molecular and transcriptional level. Our data demonstrate that low pH negatively regulates cell proliferation and survival, also, it results in cell cycle arrest, mitochondrial dynamics disorder, DNA damage as well as the impairment of proangiogenic function in a pH-dependent manner. Further transcriptome profiling identified the pivotal signaling pathways and hub genes in response to acidosis. Collectively, these findings provide strong evidences for a critical role of acidosis in ADSCs impairment with ischemic condition and suggest treatments focus on tissue pH balance and acidosis-mediated hub genes may have therapeutic potential in stem cell-based application.</p>}},
  author       = {{Huang, Kun and Wang, Qinqin and Qu, Huilong and Hu, Xinyu and Niu, Wenhao and Hultgårdh-Nilsson, Anna and Nilsson, Jan and Liang, Chun and Chen, Yihong}},
  issn         = {{2352-3204}},
  keywords     = {{Acidosis; Adipose-derived stem cells; Angiogenesis; Ischemia; pH regulation}},
  language     = {{eng}},
  pages        = {{331--343}},
  publisher    = {{Japanese Society of Regenerative Medicine}},
  series       = {{Regenerative Therapy}},
  title        = {{Effect of acidosis on adipose-derived stem cell impairment and gene expression}},
  url          = {{http://dx.doi.org/10.1016/j.reth.2024.01.010}},
  doi          = {{10.1016/j.reth.2024.01.010}},
  volume       = {{25}},
  year         = {{2024}},
}