Objective: The notochord acts as a patterning structure, playing a key role in the formation of the vertebral column, both indirectly by inducing sclerotome cell differentiation and directly by forming the nucleus pulposus of intervertebral discs. The abnormal development of the notochord results in an easy equation with a variety of birth defects. Therefore, we focused our attention on the analysis of the early stages of human notochord development by highlighting the role of progenitor stem cells involved in the origin of intervertebral discs (IVDs). Materials and methods: Eight human fetuses, ranging from 8 up to 21 weeks of gestational age, were obtained from spontaneous abortion or voluntary interruption of gestation. Samples were 10% formalin-fixed, routinely processed, and paraffin-embedded. Five micron-tick paraffin sections were obtained from each sample. Sections were stained with hematoxylin-eosin and PAS stain for a morphological examination. Tissue samples were immunostained with a commercial anti-human CD44 rabbit monoclonal antibody at 1:100 dilution. Results: Immunoreactivity for CD44 was detected in six out of eight notochords examined in this study. Reactivity for CD44 was restricted to progenitor cells giving rise to the nucleus pulposus (NP) of the developing IVDs. Positive cells showed a membranous and/or cytoplasmic immunostaining, no reactivity was observed in the nuclear compartment. CD44 expression was always restricted to IVD precursor cells, whereas cartilage precursors were devoid of labelling. Conclusions: Our study shows, for the first time, that the stem cell marker CD44 selectively marks intervertebral disc progenitor cells, paralleling their differentiation toward a discogenic phenotype. Therefore, our results suggest that CD44 plays a key role in IVD development, allowing its differentiation from surrounding undifferentiated notochordal cells toward a IVD phenotype. Given the role of CD44 in IVD development, we may hypothesize that low CD44 levels might be associated with changes in IVD development and with susceptibility to develop back pain later in life.
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