Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer’s Disease Treatment: An In Vitro Study

Abstract

The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer's disease (AD) is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs) to reduce cytotoxicity and apoptosis caused by amyloid beta (Aβ) peptide. We determined whether DPSCs can secrete the Aβ-degrading enzyme, neprilysin (NEP), and evaluated the effects of NEP expression in vitro by quantitating Aβ-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Aβ peptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degrading Aβ 1–42 in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer's disease.

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

“…66,67 The pathological change in AD is quite complicated and includes the loss of neurons, intracellular neurofibrillary tangles and the deposition of insoluble beta-amyloid peptides in the brain. [74][75][76] Furthermore, the DPSCs secretome is highly enriched in neurotrophic factors, amyloid beta-degrading enzymes (NEPs) and anti-apoptotic factors, demonstrating that DPSCs are an ideal candidate for therapy of AD. The therapeutic effect of currently available treatments for AD is still far below our expectation.…”

“…67,68 However, many of the pathological mechanisms of AD still remain unknown to us now. 74 In addition to dental stem cells themselves, conditioned medium from human dental stem cells can also improve cognitive functions in mouse AD models. DPSCs could reduce amyloid beta peptide-induced neural degeneration and apoptosis.…”

“…70 High levels of VEGF, fractalkine, RANTES, fms-related tyrosine kinase 3 and monocyte chemotactic protein 1 secreted by DPSCs could reduce amyloid beta peptide-induced neural degeneration and apoptosis. [74][75][76] Furthermore, the DPSCs secretome is highly enriched in neurotrophic factors, amyloid beta-degrading enzymes (NEPs) and anti-apoptotic factors, demonstrating that DPSCs are an ideal candidate for therapy of AD. 74 In addition to dental stem cells themselves, conditioned medium from human dental stem cells can also improve cognitive functions in mouse AD models.…”

“…[74][75][76] Furthermore, the DPSCs secretome is highly enriched in neurotrophic factors, amyloid beta-degrading enzymes (NEPs) and anti-apoptotic factors, demonstrating that DPSCs are an ideal candidate for therapy of AD. 74 In addition to dental stem cells themselves, conditioned medium from human dental stem cells can also improve cognitive functions in mouse AD models. SHED-CM may provide several neuro-reparative effects that benefit the treatment of cognitive deficits and AD treatments.…”

“…In the SCI model, both transfected SHEDs and DPSCs could inhibit early neuronal apoptosis 48,61. In the AD model, experiments showed that DPSCs could reduce apoptosis levels of okadaic acid-induced SH-SY5Y cells 70,[74][75][76]. Researchers have revealed that DPSCs can secrete apoptosis inhibitor proteins, including Bcl-2, and reduced the expression of Bas,74 an apoptotic regulator.…”