Priming of mesenchymal stem cells with a hydrosoluble form of curcumin allows keeping their mesenchymal properties for cell‐based therapy development

Abstract

Mesenchymal stem cells are increasingly studied for their use as drug‐carrier in addition to their intrinsic potential for regenerative medicine. They could be used to transport molecules with a poor bioavailability such as curcumin in order to improve their clinical usage. This natural polyphenol, well‐known for its antioxidant and anti‐inflammatory properties, has a poor solubility that limits its clinical potential. For this purpose, the use of NDS27, a curcumin salt complexed with hydroxypropyl‐beta‐cyclodextrin (HPβCD), displaying an increased solubility in aqueous solution, is preferred. This study aims to evaluate the uptake of NDS27 into skeletal muscle‐derived mesenchymal stem cells (mdMSCs) and the effects of such uptake onto their mesenchymal properties. It appeared that the uptake of NDS27 into mdMSCs is concentration‐dependent and not time‐dependent. The use of a concentration of 7 µmol/L which does not affect the viability and proliferation also allows preservation of their adhesion, invasion and T cell immunomodulatory abilities.

Equine Muscle Derived Mesenchymal Stem Cells Loaded with Water-Soluble Curcumin: Modulation of Neutrophil Activation and Enhanced Protection against Intracellular Oxidative Attack

“…Another study with hepatic HuH-7 cells showed that curcumin entered within seconds into the cells and was already maximal after 5 min but only one-twentieth of the curcumin had entered the cells [ 46 , 47 ]. The good performance of our cell loading can be explained by a different cell preparation, that in our case were suspended cells rather than adherent cells used by Colin et al [ 28 ]. Moreover, we performed the loading in an aqueous buffer (HBSS buffer) rather than in the culture medium.…”

“…Interestingly, the loading was rapid, and 20% loading capacity was reached after 2 min incubation at 37 °C ( Table 1 ). In a previous study, we loaded adherent mdMSCs with NDS27 or native curcumin for 2 h with 42 µM curcumin or NDS27, and the loading yield was only 2%, which corresponded to about 0.8 µM internalized curcumin [ 28 ]. Another study with hepatic HuH-7 cells showed that curcumin entered within seconds into the cells and was already maximal after 5 min but only one-twentieth of the curcumin had entered the cells [ 46 , 47 ].…”

“…Curcumin protected mitochondria from dysfunction by retaining the mitochondrial membrane potential (ΔΨm) and the activities of all four mitochondrial complexes (complex I, II, III, and IV) [ 51 ]. In the study performed by Colin et al [ 28 ], curcumin was localized in mitochondria of adherent mdMSCs loaded with NDS27, and they observed a transient modification of the mitochondrial metabolism which did not persist behind 24 h after cell loading. Our results confirm a potential beneficial role of curcumin on the mitochondrial function of NDS27-loaded mdMSCs, but further studies are needed to enlarge on this.…”

“…Loading equine mesenchymal stem cells from microinvasive muscle biopsies (mdMSC) with curcumin or NDS27 has previously been studied. However, the two drugs were added to the culture medium and incubated for at least 2 h before their elimination by washing and cell detachment [ 28 ].…”