From hair to heart: nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells differentiate to beating cardiac muscle cells

Abstract

We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and CD34-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and spinal cord regeneration in mouse models. In the present study, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We separated the mouse vibrissa hair follicle into 3 parts (upper, middle, and lower), and suspended each part separately in DMEM containing 10% FBS. All three parts of hair follicle differentiated to beating cardiac muscle cells as well as neurons, glial cells, keratinocytes and smooth muscle cells. The differentiation potential to cardiac muscle is greatest in the upper part of the follicle. The beat rate of the cardiac muscle cells was stimulated by isoproterenol and inhibited by propanolol. HAP stem cells have potential for regenerative medicine for heart disease as well as nerve and spinal cord repair.

Human hair-follicle associated pluripotent (hHAP) stem cells differentiate to cardiac-muscle cells

“…The present study, along with our previous studies of HAP stem cells, [5][6][7][8][9][10][11][12][13]16,17 demonstrate their superiority over ES and iPS cells for regenerative medicine due to HAP stem cells facile accessibility from any patient, their lack of tumorigenicity, lack of the need to insert foreign genes and lack of ethical problems. It is expected in the near future that hHAP stem cells will be the predominant stem cells used for regenerative medicine.…”

“…We then demonstrated that mouse HAP stem cells differentiate to beating cardiac-muscle cells. 11 Isoproterenol stimulated mouse HAP stem cells to differentiate to cardiac-muscle cells in large numbers in culture. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, stimulated the cardiac-muscle cells to form tissue sheets of beating heart muscle cells.…”

Aging hair follicles rejuvenated by transplantation to a young subcutaneous environment

“…5 The hair follicle, which cycles through telogen (resting), anagen (growing), and catagen (regression) throughout the life of mammals, undergoes obvious age-related changes including hair loss. 6 The hair follicle contains hair-follicle-associated pluripotent (HAP) stem cells, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] which may also deteriorate during aging.…”

Cardiac Nestin⁺ Cells Derived from Early Stage of Dilated Cardiomyopathy Enhanced the Survival of the Doxorubicin-Injured Cardiac Muscle HL-1 Cells

“…Nestin expression in animal models of DCM: It has been reported that Nestin is expressed in adult hearts and up-regulated in the damaged hearts. 30) To systemically assess the expression of Nestin during DCM process, we used Nestin-GFP transgenic mice; cells containing with GFP immunoreactivity were expressed Nestin; thus, we could analyze Nestin expression during DCM pathogenesis by detecting GFP under fluorescence microscope. The result of immunofluorescence staining showed that myocardial Nestin-GFP + cells were markedly up-regulated early in the animal model of DCM (from day 0 to day 6) and then significantly decreased lately (from day 6 to day 30) (Figure 2A), and the statistics data showed that Nestin-GFP cells in a field size of mm 2 on day 6 (126.4 ± 6.635) increased to a large extent compared with day 0 (11.49 ± 6.634) and then reduced gradually (day 30 data show 3.83 ± 3.83) ( Figure 2B).…”