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

Abstract

AIMS:

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.

METHODS AND RESULTS:

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.

CONCLUSION:

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.

• Authors: Rubin Tan, Jiansha Li, Xiaochun Peng, Liping Zhu, Lei Cai, Tao Wang, Yuan Su, Kaikobad Irani, Qinghua Hu
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 100 Issue 1 Pg. 19-27 (Oct 01 2013) ISSN: 1755-3245 [Electronic] England
• PMID: 23801767 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
• Calcium

Topics

• Animals
• Bone Marrow Cells (enzymology)
• Calcium (metabolism)
• Cells, Cultured
• Familial Primary Pulmonary Hypertension
• Female
• Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) (physiology)
• Hypertension, Pulmonary (therapy)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (physiology)
• Mice
• Mice, Inbred C57BL
• Sex Characteristics