Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs-treated cells were found to restore gradually with re-elongation of retracted dendrites. Meanwhile, Cell Counting Kit-8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs-treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α-tubulin and F-actin demonstrated that the hDPSCs-treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD.

HGF Mediates Clinical‐Grade Human Umbilical Cord‐Derived Mesenchymal Stem Cells Improved Functional Recovery in a Senescence‐Accelerated Mouse Model of Alzheimer's Disease

“…To further explore whether hUC‐MSCs could restore damaged neural cells, we used an in vitro AD cell model of tauopathy induced by okadaic acid (OA) which we have established in a previous work. [ 19 ] According to different sensitivities to OA, primary neurons and SH‐SY5Y cells were induced by incubation with OA at a final concentration of 10 n m for 4 h and 20 n m for 24 h (Figure S3, Supporting Information). We analyzed the cell morphology, mitochondrial function, cell viability, subcellular structure and phosphorylation level of tau protein to assess the degree of damage induced by OA and the restorative effects with conditioned medium (CM) of hUC‐MSCs.…”

“…[ 37,38 ] Here, we used an in vitro AD cell model of tauopathy induced by OA which is a classic method to study tau diseases in vitro [ 39,40 ] that we have established in previous work. [ 19 ] By using this model, we demonstrated that hUC‐MSCs could effectively recover and rescue OA‐induced neurological damage, including improving cytoskeleton arrangement and mitochondrial function, restoring dendritic length and dendritic spines number, and partially inhibiting tau hyperphosphorylation (Figure 3 and Figure S4, Supporting Information). Through in vivo and in vitro models, we have more comprehensive evidence that hUC‐MSCs could effectively treat AD, at least partially by regulating tau hyperphosphorylation.…”

Dental pulp stem cells and the management of neurological diseases: An update

“…Because a definitive cure has not been reached so far, stem cell therapies have been investigated for their usefulness in rescuing or even preventing neural loss in patients with AD (Brookmeyer et al, ). Clinical trials are currently ongoing, and various preclinical studies have been performed using AD animal models (Kim et al, ; Li et al, ; Wang et al, ; Zhang et al, ). Ahmed et al studied the therapeutic potential of secretome derived from DPSCs to decrease apoptosis and cytotoxicity mediated by amyloid β peptide (Ahmed, Murakami, Hirose, & Nakashima, ).…”

Advances of tooth‐derived stem cells in neural diseases treatments and nerve tissue regeneration

“…For a deep investigation of AD treatments, AD mouse models have been created by overexpression amyloid precursor protein. Okadaic acid (OA)-induced SH-SY5Y cells present a rounder shape with retracted cytoplasm and poor adherence 70. AD cell model is also frequently used in researches.…”

“…Okadaic acid (OA)-induced SH-SY5Y cells present a rounder shape with retracted cytoplasm and poor adherence 70. Apart from the above-mentioned mechanisms, DPSCs possess the ability to promote neural repair in in vitro AD model 70. Several MSCs, including BMSCs and ADSCs, have been proven to be beneficial in AD recovery 71.…”