Proteomics reveals the potential mechanism of Tanshinone IIA in promoting the Ex Vivo expansion of human bone marrow mesenchymal stem cells

Pei Yuan; Hong-Yan Qin; Jia-Yun Wei; Geshuyi Chen; Xun Li

doi:10.1016/j.reth.2022.11.004

Proteomics reveals the potential mechanism of Tanshinone IIA in promoting the Ex Vivo expansion of human bone marrow mesenchymal stem cells

Regen Ther. 2022 Nov 24:21:560-573. doi: 10.1016/j.reth.2022.11.004. eCollection 2022 Dec.

Authors

Pei Yuan¹, Hong-Yan Qin², Jia-Yun Wei¹, Geshuyi Chen¹, Xun Li^{1

3

4

5}

Affiliations

¹ The First Clinical Medical College, Lanzhou University, Lanzhou, China.
² Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, China.
³ The Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.
⁴ Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, China.
⁵ Hepatopancreatobiliary Surgery Institute of Gansu Province, Lanzhou, China.

Abstract

Introduction: Bone marrow mesenchymal stem cells (BMSCs) are a promising cell type for tissue engineering, however, the application of BMSCs is largely hampered by the limited number harvested from bone marrow cells. The methods or strategies that focused on promoting the capacity of BMSCs expansion ex vivo become more and more important. Tanshinone IIA (Tan IIA), the main active components of Danshen, has been found to promote BMSCs proliferation, but the underlying mechanism is still unclear. The aim of this study is to explore the effect and underlying mechanism of Tan IIA on the expansion capacity of hBMSCs ex vivo.

Methods: In this present study, the effect of Tan IIA on the expansion capacity of BMSCs from human was investigated, and quantitative proteome analysis was applied furtherly to identify the differentially expressed proteins (DEPs) and the molecular signaling pathways in Tan IIA-treated hBMSCs. Finally, molecular biology skills were employed to verify the proposed mechanism of Tan IIA in promoting hBMSCs expansion.

Results: The results showed that a total of 84 DEPs were identified, of which 51 proteins were upregulated and 33 proteins were downregulated. Besides, Tan IIA could promote hBMSCs proliferation by regulating the progression of S phase via increasing the release of fibroblast growth factor 2 (FGF2), FGF-mediated PI3K/AKT signaling pathways may play an important role in Tan IIA's effect on hBMSCs expansion.

Conclusions: This study employed molecular biology skills combined with quantitative proteome analysis, to some extent, clarified the mechanism of Tan IIA's effect on promoting hBMSCs proliferation, and will give a hint that Tan IIA may have the potential to be used for BMSCs applications in cell therapies in the future.

Keywords: Autocrine; BMSCs, bone marrow mesenchymal stem cells; Bone marrow mesenchymal stem cells; CDK, cyclin-dependent kinase; COG, Clusters of Orthologous Groups of proteins; DEPs, differentially expressed proteins; DMSO, dimethyl sulfoxide; EdU, 5' Ethynyl 2' deoxyuridine; Expansion; FC, Fold Change; FDR, false discovery rate; FGF1/2, fibroblast growth factor 1/2; FGFR, FGF receptor; Fibroblast growth factor 2; GO, Gene Ontology; HPLC, high performance liquid chromatography; KEGG, Encyclopedia of Genes and Genomes; LC-MS, liquid chromatography-mass spectrometry; MTT, Three-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PCNA, proliferating cell nuclear antigen; PPI, protein–protein interactions; Proteomics; TEAB, triethylammonium bicarbonate; TMT, tendam mass tags; Tan IIA, Tanshinone IIA; Tanshinone IIA.