Proliferation of rat cardiac stem cells is induced by 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside in vitro.
OBJECTIVE
To study the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG) on proliferation of rat cardiac stem cells (CSCs) in vitro.


METHODS
C-kit(+) cells were isolated from neonatal (1 day old) Sprague-Dawley rats by using flow cytometry. Optimal THSG treatment times and doses for growth of CSCs were analyzed. CSCs were treated with various THSG doses (0, 1, 10, and 100 μM) for 12h.


RESULTS
Sorted c-kit(+) cells exhibited self-renewing and clonogenic capabilities. Cell Counting Kit (CCK-8) and Proliferating Cell Nuclear Antigen (PCNA) ELISA test positive cells were significantly increased in THSG-treated groups compared with untreated controls. The percentage of S-phase cells also increased after THSG treatment. Moreover, we show that some c-kit(+) cells spontaneously express vascular endothelial growth factor (VEGF), T-box transcription factor (Tbx5), hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2), hyperpolarization-activated cyclic nucleotide gated 4 (HCN4), alpha myosin heavy chain (αMHC), and beta myosin heavy chain (βMHC) mRNA, and stem cell antigen 1 (Sca-1), cardiac troponin-I, GATA-4, Nkx2.5, and connexin 43 protein were also assessed in CSCs. However, their expression was significantly increased with THSG treatment when compared to untreated controls.


CONCLUSIONS
THSG can increase proliferation of rat CSCs in vitro and thus, shows promise as a potential treatment strategy for stimulating endogenous stem cells to help repair the injured heart after myocardial infarction in patients.
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Fan
F
Song
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Jing
J
Zhao
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Fei
F
Hua
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Lun
L
Nian
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Xuan-Xuan
XX
Zhou
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Qian
Q
Yang
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Yan-Hua
YH
Xie
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China.
Hai-Feng
HF
Tang
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China. Electronic address: sunjiy@fmmu.edu.cn.
Ji-Yuan
JY
Sun
Institute of Material Medical, School of Pharmacy, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China; Collaborative Innovation Center for Chinese Medicine in Qinba Moutains, The Fourth Military Medical University, No. 169, Changle West Road, Xi'an 710032, China. Electronic address: wangsiw@fmmu.edu.cn.
Si-Wang
SW
Wang
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005960:Glucosides / Q000494:pharmacology*; D066298:In Vitro Techniques; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019089:Stem Cell Factor / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017931:DNA Primers; D005960:Glucosides; D018809:Proliferating Cell Nuclear Antigen; D019089:Stem Cell Factor; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
2, 3, 5, 4′-Tetrahydroxystilbene-2-O-β-d-glucoside proliferation; Cardiac stem cells; Myocardial infarction