Isoproterenol directs hair follicle-associated pluripotent (HAP) stem cells to differentiate in vitro to cardiac muscle cells which can be induced to form beating heart-muscle tissue sheets

CELL CYCLE, 2016 · DOI: 10.1080/15384101.2016.1146837 · Published: March 3, 2016

Cardiovascular Science Regenerative Medicine & Stem Cells

Simple Explanation

Hair follicle-associated pluripotent (HAP) stem cells, found in hair follicles, can transform into various cell types. This study explores their potential to become heart muscle cells. The research demonstrates that isoproterenol, a medication, significantly boosts the transformation of HAP stem cells into heart muscle cells in a lab setting. Furthermore, the addition of specific growth factors (activin A, BMP4, and bFGF) alongside isoproterenol encourages these heart muscle cells to form functional, beating tissue sheets, mimicking heart muscle.

Study Duration

14 days

Participants

GFP transgenic mice

Evidence Level

Not specified

Key Findings

1
Isoproterenol significantly enhances the differentiation of HAP stem cells into cardiac muscle cells in vitro compared to non-supplemented conditions.
2
The combination of isoproterenol, activin A, BMP4, and bFGF induces HAP stem cells to form beating cardiac-muscle tissue sheets.
3
Cardiac-muscle tissue sheets contain cardiac muscle cells, vascular endothelial cells, and smooth muscle actin-positive cells.

Research Summary

This study investigates the potential of hair follicle-associated pluripotent (HAP) stem cells to differentiate into cardiac muscle cells and form beating heart-muscle tissue sheets in vitro. The findings demonstrate that isoproterenol directs HAP stem cells to differentiate into cardiac muscle cells, and the addition of activin A, BMP4, and bFGF further induces the formation of beating cardiac-muscle tissue sheets. The resulting cardiac-muscle tissue sheets contain cardiac muscle cells, vascular endothelial cells, and smooth muscle actin-positive cells, suggesting their potential for use in heart muscle regeneration.

Practical Implications

Cardiac Regeneration Therapy

HAP stem cells can be used to grow nestin-expressing HAP stem cells in sufficient quantities to differentiate into heart muscle sheets to be used for heart muscle regeneration in the clinic.

Drug Development

Isoproterenol and other growth factors can be used to direct differentiation of HAP stem cells into cardiac muscle cells.

Tissue Engineering

The method described here is appropriate for future use of human hair follicles to grow nestin-expressing HAP stem cells in sufficient quantities to differentiate into heart muscle sheets.

Study Limitations

1
The study was performed in vitro, and further research is needed to assess the efficacy and safety of HAP stem cell-derived cardiac muscle sheets in vivo.
2
The study used mouse vibrissa hair follicles, and further research is needed to determine if human hair follicles can be used to obtain HAP stem cells with similar differentiation potential.
3
The mechanism by which isoproterenol and growth factors induce HAP stem cell differentiation into cardiac muscle cells is not fully understood and warrants further investigation.

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