Telocytes in human heart valves

Abstract

Valve interstitial cells (VICs) are responsible for maintaining the structural integrity and dynamic behaviour of the valve. Telocytes (TCs), a peculiar type of interstitial cells, have been recently identified by Popescu's group in epicardium, myocardium and endocardium (visit www.telocytes.com). The presence of TCs has been identified in atria, ventricles and many other tissues and organ, but not yet in heart valves. We used transmission electron microscopy and immunofluorescence methods (double labelling for CD34 and c-kit, or vimentin, or PDGF Receptor-β) to provide evidence for the existence of TCs in human heart valves, including mitral valve, tricuspid valve and aortic valve. TCs are found in both apex and base of heart valves, with a similar density of 27-28 cells/mm(2) in mitral valve, tricuspid valve and aortic valve. Since TCs are known for the participation in regeneration or repair biological processes, it remains to be determined how TCs contributes to the valve attempts to re-establish normal structure and function following injury, especially a complex junction was found between TCs and a putative stem (progenitor) cell.

Keywords: C-kit; CD34; PDGF-β; heart valves; telocytes; telopodes; vimentin.

Fig. 1

Electron microscope images show the existence of telocytes (TCs) in human heart valves. (A) TCs with telopodes (Tps) in the interstitial layer of aortic valve. (B) A TC with Tps in mitral valve. (C) TCs with Tps in tricuspid valve. Note the upper Tp which is more than 30 μm long. (D) A typical TC with Tps in tricuspid valve. ECM: extracellular matrix.

Fig. 2

Electron microscope images show a telocyte (TC) in human mitral valve in close contact with a putative stem cell (SC). (A) A TC with telopodes (Tps) is feeding a SC. (B) Higher magnification of the TC with Tps. m: mitochondrion. (C) Higher magnification of Tps and a putative SC. (D) Higher magnification showing the junction between Tps and a putative SC. N: nucleus; c: centriole; ER: Endoplasmic reticulum; fR: free ribosomes; ECM: extracellular matrix.

Fig. 3

Human aortic valve: immunofluorescence labelling shows telocytes (TCs). Laser scanning confocol microscopy: CD34 and c-kit double immunofluorescence labelling showing (A) CD34 (green), (B) c-kit (red) and (C) co-localization (yellow) in a telocyte. CD34 and vimentin double immunofluorescence labelling showing (D) CD34 (green), (E) vimentin (red) and (F) co-localization (yellow) in a telocyte. CD34 and PDGF Receptor-β double immunofluorescence labelling showing (G) CD34 (green), (H) PDGFR-β (red) and (I) co-localization (yellow) in a telocyte. Nuclei are counterstained with DAPI (blue). Original magnification 400×; scale bar = 20 μm.

Fig. 4

Human mitral valve: immunofluorescence labelling shows telocytes (TCs). Laser scanning confocol microscopy: CD34 and c-kit double immunofluorescence labelling showing (A) CD34 (green), (B) c-kit (red) and (C) co-localization (yellow) in a telocyte. CD34 and vimentin double immunofluorescence labelling showing (D) CD34 (green), (E) vimentin (red) and (F) co-localization (yellow) in a telocyte. CD34 and PDGF Receptor-β double immunofluorescence labelling showing (G) CD34 (green), (H) PDGFR-β (red) and (I) co-localization (yellow) in a telocyte. Nuclei are counterstained with DAPI (blue). Original magnification 400×; scale bar = 20 μm.

Fig. 5

Human tricuspid valve: immunofluorescence labelling shows telocytes (TCs). Laser scanning confocol microscopy: CD34 and c-kit double immunofluorescence labelling showing (A) CD34 (green), (B) c-kit (red) and (C) co-localization (yellow) in a telocyte. CD34 and vimentin double immunofluorescence labelling showing (D) CD34 (green), (E) vimentin (red) and (F) co-localization (yellow) in a telocyte. CD34 and PDGF Receptor-β double immunofluorescence labelling showing (G) CD34 (green), (H) PDGFR-β (red) and (I) co-localization (yellow) in a telocyte. Nuclei are counterstained with DAPI (blue). Original magnification 400×; scale bar = 20 μm.