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GAPDH is critical for superior efficacy of female bone marrow-derived mesenchymal stem cells on pulmonary hypertension
Journal article   Open access   Peer reviewed

GAPDH is critical for superior efficacy of female bone marrow-derived mesenchymal stem cells on pulmonary hypertension

Rubin Tan, Jiansha Li, Xiaochun Peng, Liping Zhu, Lei Cai, Tao Wang, Yuan Su, Kaikobad Irani and Qinghua Hu
Cardiovascular research, Vol.100(1), pp.19-27
10/01/2013
DOI: 10.1093/cvr/cvt165
PMID: 23801767
url
https://doi.org/10.1093/cvr/cvt165View
Published (Version of record) Open Access

Abstract

Pulmonary arterial hypertension, a chronic lung disease, remains an unacceptable prognosis despite significant advances in conventional therapies. Stem cell therapy represents a novel and effective modality. This study was aimed to add new insight in gender differences of bone marrow-derived mesenchymal stem cells on therapy against pulmonary arterial hypertension and the underlying mechanism. By in vivo experiments, we showed for the first time female bone marrow-derived mesenchymal stem cells possessed a better therapeutic potential against monocrotaline-induced pulmonary arterial hypertension in C57BL/6J mice compared with male counterparts. In vitro experiments demonstrated superior function of female bone marrow-derived mesenchymal stem cells in cell proliferation, migration and [Ca(2+)]i kinetics. Moreover, we unexpectedly found that, compared with male ones, female bone marrow-derived mesenchymal stem cells had a higher expression level of glyceraldehyde-3-phosphate dehydrogenase and manipulations of its expression in female or male bone marrow-derived mesenchymal stem cells profoundly affected their cellular behaviours and therapeutic efficacies against pulmonary arterial hypertension. Our results suggest that glyceraldehyde-3-phosphate dehydrogenase plays a critical role in determining the superior functions of female bone marrow-derived mesenchymal stem cells in cell therapy against pulmonary arterial hypertension by regulating [Ca(2+)]i signal-associated cellular behaviours.
Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - physiology Bone Marrow Cells - enzymology Calcium - metabolism Mice, Inbred C57BL Cells, Cultured Familial Primary Pulmonary Hypertension Male Sex Characteristics Hypertension, Pulmonary - therapy Animals Female Mice Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells - physiology

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