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

Abstract

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.

Keywords: Europium; Lithium; Mesenchymal stem cells; Nanohydroxyapatite; Osteogenesis; Regenerative medicine; Samarium; Theranostics.