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

• Published in: Regenerative therapy Vol. 25; pp. 331 - 343
• Main Authors: Huang, Kun, Wang, Qinqin, Qu, Huilong, Hu, Xinyu, Niu, Wenhao, Hultgårdh-Nilsson, Anna, Nilsson, Jan, Liang, Chun, Chen, Yihong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2024; Japanese Society for Regenerative Medicine; Elsevier
• Subjects: Acidosis; Adipose-derived stem cells; Angiogenesis; Basic Medicine; Cell and Molecular Biology; Cell- och molekylärbiologi; Ischemia; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Original; pH regulation; CLI; CDKN1A; SHC1; PPI; Adipose-derived stem cells; PIK3R1; pH regulation; CDC42; Angiogenesis; LDPI; DEGs; Ischemia; ABL1; KEGG; E2F7; Tomm20; MMP2; qRT-PCR; GO; MCC; VEGF-A; ADSC; ECM; IL-6; PAD; FUCCI; PI; STRING; KRAS; Acidosis; CRK; TP53; HUVECs
• ISSN: 2352-3204; 2352-3204
• DOI: 10.1016/j.reth.2024.01.010

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.
•Microdialysis reveals the raised lactate and reduced glucose level in hindlimb muscle during 72 hours of ischemia.•Cell cycle indicator FUCCI system together with time-lapse imaging confirm the G1 arrest in ADSCs with acidic exposures.•VEGF-A, ABL1, IL-6, CDC42, KRAS, SHC1, PIK3R1 and TP53 are identified as acidosis-mediated hub genes.