TGFβ-induced osteogenic potential of human amniotic fluid stem cells via CD73-generated adenosine production

• Published in: Scientific reports Vol. 7; no. 1; pp. 6601 - 11
• Main Authors: Hau, Kwan-Leong, Ranzoni, Anna Maria, Vlahova, Filipa, Hawkins, Kate, De Coppi, Paolo, David, Anna L., Guillot, Pascale V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.07.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/106; 13/31; 14/63; 38/39; 5'-Nucleotidase - metabolism; 631/532; 631/532/1360; Adenosine; Adenosine - metabolism; Amniotic fluid; Amniotic Fluid - cytology; CD73 antigen; Cell culture; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Embryos; GPI-Linked Proteins - metabolism; Humanities and Social Sciences; Humans; Mesenchyme; multidisciplinary; Osteogenesis; Science; Science (multidisciplinary); Stem cells; Stem Cells - drug effects; Therapeutic applications; Transforming Growth Factor beta - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-06780-1

The human amniotic fluid stem cell (hAFSC) population consists of two morphologically distinct subtypes, spindle-shaped and round-shaped cells (SS-hAFSCs and RS-hAFSCs). Whilst SS-hAFSCs are routinely expanded in mesenchymal-type (MT) conditions, we previously showed that they acquire broader differentiation potential when cultured under embryonic-type (ET) conditions. However, the effects of culture conditions on RS-hAFSCs have not been determined. Here, we show that culturing RS-hAFSCs under ET conditions confers faster proliferation and enhances the efficiency of osteogenic differentiation of the cells. We show that this occurs via TGFβ-induced activation of CD73 and the associated increase in the generation of extracellular adenosine. Our data demonstrate that culture conditions are decisive for the expansion of hAFSCs and that TGFβ present in ET conditions causes the phenotype of RS-hAFSCs to revert to an earlier state of stemness. Cultivating RS-hAFSCs in ET conditions with TGFβ may therefore increase their therapeutic potential for clinical applications.