Lithium ions (Li+) and nanohydroxyapatite (nHAp) doped with Li+ enhance expression of late osteogenic markers in adipose-derived stem cells. Potential theranostic application of nHAp doped with Li+ and co-doped with europium (III) and samarium (III) ions

• Published in: Materials Science & Engineering C 2019-06, Vol.99, p.1257-1273
• Main Authors: Alicka, M., Sobierajska, P., Kornicka, K., Wiglusz, R.J., Marycz, K.
• Format: Article
• Language: English
• Subjects: Adipose tissue; Apoptosis; Biocompatibility; Biological activity; Cell proliferation; Differentiation (biology); Europium; Gene expression; Glycogen; Glycogen synthase kinase 3; Ions; Kinases; Lithium; Lithium ions; Materials science; Mesenchymal stem cells; Metal ions; Mitochondria; mRNA; Nanohydroxyapatite; Osteogenesis; Precision medicine; Rare earth elements; Regenerative medicine; Samarium; Stem cells; Theranostics; Tissue engineering; β-Catenin
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.02.073

Lithium (Li+) ion due to its excellent bioactivity is one of the most well-studied element in bone-tissue engineering. In this study, we fabricated nanohydroxyapatite (nHAp) doped with Li+ ions (5 mol% Li+:nHAp) and co-doped with lanthanide ions. We investigated the effects of nHAp, 5 mol% Li+:nHAp or Li+ alone, on osteogenic differentiation of human Adipose Tissue-derived Stem Cells (hASCs), their proliferation, mitochondrial dynamics and apoptosis. Moreover, we monitored cell proliferation after treatment with samarium (III) (Sm3+) and europium (III) (Eu3+) ions co-doped 5 mol% Li+:nHAp as well as their luminescent property. The hASCs treated with 5 mol% Li+:nHAp and Li+ ions proliferated more rapidly and differentiated effectively than control cells without undergoing apoptosis. Both, 5 mol% Li+:nHAp and Li+ ions improved osteogenic differentiation of hASCs. Moreover they decreased expression of glycogen synthase kinase 3β (GSK3β) while increased β-catenin mRNA level. In addition, Li+, nHAp and 5 mol% Li+:nHAp improved mitochondrial dynamics and enhanced expression of neural differentiation marker genes. Collectively, the study indicates on pro-osteogenic and anti-apoptotic properties of nHAp doped with Li+ and Li+ alone. Moreover, unique properties of 5 mol% Li+:nHAp and 5 mol% Li+:nHAp co-doped with rare earth ions, such as Sm3+ and Eu3+ have shed a promising light on their potential application in theranostics. [Display omitted] •Nanohydroxyapatite (nHAp) and doped with Li+ ions, and co-doped with Eu3+ or Sm3+ ions were successfully synthesized•Li+ ions and 5 mol% Li+:nHAp significantly stimulate proliferation of human Adipose tissue-derived Stem Cells (hASCs)•Li+ ions, nHAp and 5 mol% Li+:nHAp enhance expression of late osteogenic markers in hASCs•Li+ ions, nHAp and 5 mol% Li+:nHAp inhibit apoptosis and stimulate mitochondrial dynamics•nHAp doped with Li+ ions and co-doped with Eu3+ and Sm3+ ions have potentially practical applicability as theranostic agents