Intracardiac Injection of Dental Pulp Stem Cells After Neonatal Hypoxia-Ischemia Prevents Cognitive Deficits in Rats

Abstract Background Duchenne muscular dystrophy (DMD) is an inherited progressive disorder that causes skeletal and cardiac muscle deterioration with chronic inflammation. Dental pulp stem cells (DPSCs) are attractive candidates for cell-based strategies for DMD because of their immunosuppressive properties. Therefore, we hypothesized that systemic treatment with DPSCs might show therapeutic benefits as an anti-inflammatory therapy. Methods To investigate the potential benefits of DPSC transplantation for DMD, we examined disease progression in a DMD animal model, mdx mice, by comparing them with different systemic treatment conditions. The DPSC-treated model, a canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to that of DMD patients, also underwent comprehensive analysis, including histopathological findings, muscle function, and locomotor activity. Results We demonstrated a therapeutic strategy for long-term functional recovery in DMD using repeated DPSC administration. DPSC-treated mdx mice and CXMDJ showed no serious adverse events. MRI findings and muscle histology suggested that DPSC treatment downregulated severe inflammation in DMD muscles and demonstrated a milder phenotype after DPSC treatment. DPSC-treated models showed increased recovery in grip-hand strength and improved tetanic force and home cage activity. Interestingly, maintenance of long-term running capability and stabilized cardiac function was also observed in 1-year-old DPSC-treated CXMDJ. Conclusions We developed a novel strategy for the safe and effective transplantation of DPSCs for DMD recovery, which included repeated systemic injection to regulate inflammation at a young age. This is the first report on the efficacy of a systemic DPSC treatment, from which we can propose that DPSCs may play an important role in delaying the DMD disease phenotype.

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Development of novel gene carrier using modified nano hydroxyapatite derived from equine bone for osteogenic differentiation of dental pulp stem cells

Bioactive Materials ◽

10.1016/j.bioactmat.2021.01.020 ◽

2021 ◽

Vol 6 (9) ◽

pp. 2742-2751

Author(s):

Myung Chul Lee ◽

Hoon Seonwoo ◽

Kyoung Je Jang ◽

Shambhavi Pandey ◽

Jaewoon Lim ◽

...

Keyword(s):

Stem Cells ◽

Osteogenic Differentiation ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Gene Carrier ◽

Novel Gene ◽

Equine Bone

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Chrysin induces osteogenic differentiation of human dental pulp stem cells

Experimental Cell Research ◽

10.1016/j.yexcr.2020.112466 ◽

2021 ◽

Vol 400 (2) ◽

pp. 112466

Author(s):

J.F. Huo ◽

M.L. Zhang ◽

X.X. Wang ◽

D.H. Zou

Keyword(s):

Stem Cells ◽

Osteogenic Differentiation ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Human Dental Pulp

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Effects of CGRP-Primed Dental Pulp Stem Cells on Trigeminal Sensory Neurons

Journal of Dental Research ◽

10.1177/00220345211004872 ◽

2021 ◽

pp. 002203452110048

Author(s):

B. Michot ◽

S.M. Casey ◽

J.L. Gibbs

Keyword(s):

Stem Cells ◽

Sensory Neurons ◽

Dental Pulp ◽

Quantitative Polymerase Chain Reaction ◽

Primary Cultures ◽

Dental Pulp Stem Cells ◽

Afferent Activity ◽

Cytokines And Chemokines ◽

Trigeminal Neurons ◽

Trigeminal Neuron

Dental pulp stem cells (DPSCs) are important in tooth physiology, contributing to development, repair, regeneration, and immunomodulatory processes. However, their role in inflammatory mechanisms underlying pulpitis is not well understood. We evaluated the influence of DPSCs stimulated with calcitonin gene-related peptide (CGRP), a proinflammatory neuropeptide, on the expression of mediators released from DPSCs and the effect of these mediators on sensory neuron activity. Human DPSCs were treated with either control media or media containing CGRP (10−8 M) for 7 d, and the conditioned media (CM) containing DPSC-released mediators was collected. The expression of cytokines and chemokines from DPSCs was evaluated by reverse transcription quantitative polymerase chain reaction. The effects of the CM from CGRP-primed DPSCs (primed DPSC-CM) were evaluated on sensory afferents by using primary cultures of mouse trigeminal neurons and an organotypic model of cultured human pulp slices. Mouse trigeminal neurons and human pulp explants were pretreated for 24 h with control or primed DPSC-CM and then stimulated with capsaicin. Afferent activity was measured by quantifying the response to capsaicin via live cell calcium imaging in mouse neurons and CGRP released from pulp explants. Gene expression analysis showed that primed DPSCs overexpressed some proinflammatory cytokines and chemokines, including chemokines CXCL1 and CXCL8, which are both agonists of the receptor CXCR2 expressed in sensory neurons. Primed DPSC-CM increased human pulp sensory afferent activity as compared with control DPSC-CM. Similarly, primed DPSC-CM increased the intensity of calcium responses in cultured mouse trigeminal neurons. Furthermore, the CXCR2 antagonist SB225002 prevented trigeminal neuron sensitization to capsaicin induced by primed DPSC-CM. In conclusion, mediators released by DPSCs, primed with the proinflammatory mediator CGRP, induce neuronal sensitization through CXCR2 receptor. These data suggest that DPSCs might contribute to pain symptoms that develop in pulpitis.

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