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

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.

Wang, QinqinSecond Affiliated Hospital of Naval Medical University (författare)
Qu, HuilongSecond Affiliated Hospital of Naval Medical University (författare)
Hu, XinyuRadboud University Nijmegen (författare)
Niu, WenhaoSecond Affiliated Hospital of Naval Medical University (författare)
Hultgårdh-Nilsson, AnnaLund University,Lunds universitet,Kärlväggsbiologi,Forskargrupper vid Lunds universitet,Vessel Wall Biology,Lund University Research Groups(Swepub:lu)medk-ahu (författare)
Nilsson, JanLund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups(Swepub:lu)medf-jni (författare)
Liang, ChunSecond Affiliated Hospital of Naval Medical University(Swepub:lu)ch6727li (författare)
Chen, YihongLund University,Lunds universitet,Kärlväggsbiologi,Forskargrupper vid Lunds universitet,Vessel Wall Biology,Lund University Research Groups,Second Affiliated Hospital of Naval Medical University(Swepub:lu)yi3845ch (författare)
Second Affiliated Hospital of Naval Medical UniversityRadboud University Nijmegen (creator_code:org_t)

Av författaren/redakt...: Huang, Kun; Wang, Qinqin; Qu, Huilong; Hu, Xinyu; Niu, Wenhao; Hultgårdh-Nilsso ...; visa fler...; Nilsson, Jan; Liang, Chun; Chen, Yihong; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

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