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In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells
Published on: August 9, 2017
Stromal cell-derived factor-1 promotes bone marrow-derived cells differentiation to cardiomyocyte phenotypes in vitro
1Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Insights
Stromal cell-derived factor-1 (SDF-1) promotes bone marrow-derived cells (BMDC) to become heart cells in vitro. This suggests SDF-1 plays a role in cardiomyogenesis via the SDF-1/CXCR4/PI3K/Akt pathway.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Molecular Medicine
Background:
- Bone marrow-derived cells (BMDC) show potential for differentiating into cardiomyocytes.
- Stromal cell-derived factor-1 (SDF-1) is upregulated in infarcted myocardium and recruits BMDC.
- The role of SDF-1 in BMDC cardiomyogenesis is currently unknown.
Purpose of the Study:
- To investigate the role of SDF-1 in the differentiation of BMDC into cardiomyocytes.
- To explore the molecular mechanisms underlying SDF-1-induced cardiomyogenesis.
Main Methods:
- Adherent BMDC were cultured with SDF-1.
- Specific inhibitors for PI3K, CXCR4, or Akt were used in combination with SDF-1.
- Cardiac-specific gene and protein expression in BMDC was analyzed after 2 weeks.
Main Results:
- BMDC cultured with SDF-1 expressed cardiac-specific mRNAs (NKX2.5, atrial natriuretic factor, heavy chain beta-myosin) and proteins (troponin I, heavy chain cardiac myosin).
- Co-treatment with CXCR4, PI3K, or Akt inhibitors partially reduced the expression of these cardiac markers.
- These findings indicate SDF-1 can induce cardiomyogenic phenotypes in BMDC in vitro.
Conclusions:
- SDF-1 promotes BMDC differentiation into cardiomyocyte phenotypes in vitro, extending beyond its known roles in cell mobilization and homing.
- The SDF-1/CXCR4/PI3K/Akt signaling pathway is implicated as a key mechanism in regulating BMDC cardiomyogenesis.
- This study provides novel insights into the potential of SDF-1 in cardiac regenerative medicine.
Objective:
Recent studies have demonstrated the potential of bone marrow-derived cells (BMDC) to differentiate into cardiomyocytes. Up-regulation of stromal cell-derived factor-1 (SDF-1), a member of the chemokine CXC subfamily, mediating recruitment of BMDC has been documented in infarcted myocardium; however, it remains unknown whether SDF-1 plays a role in cardiomyogenesis of BMDC.
Materials And Methods:
Adherent BMDCs were cultured with SDF-1, or specific inhibitor for PI3K, CXCR4 or Akt with SDF-1, respectively. After 2 weeks, mRNAs and proteins from BMDCs were examined.
Results:
Two weeks after supplementation with SDF-1, either murine or human adherent BMDC cultured in vitro expressed cardiac specific mRNAs (NKX2.5, atrial natriuretic factor and heavy chain beta-myosin) and proteins (troponin I and heavy chain cardiac myosin), and expression levels were partly decreased by combined treatment of CXCR4, PI3K or Akt inhibitor, with SDF-1.
Conclusions:
The novel findings suggest that beyond its role in mobilization and homing of BMDC, SDF-1 can promote BMDC to give rise to cardiomyocyte phenotypes in vitro, and the SDF-1/CXCR4/PI3K/Akt pathway may be one of the molecular mechanisms regulating cardiomyogenesis.
