The Importance of Stem Cells Isolated from Human Dental Pulp and Exfoliated Deciduous Teeth as Therapeutic Approach in Nervous System Pathologies
Abstract
:1. Introduction
2. Types of Stem Cells for Therapy of Neurodegenerative Diseases
3. Induction of Neuronal Lineages in DPSCs and SHEDs
4. Relevance of DPSCs and SHEDs in Neurodegenerative Diseases
4.1. Potential Therapeutic Application of DPSCs and SHEDs for Sensory System Disorders
4.2. DPSCs in Alzhemier’s Disease Models
4.3. DPSCs and SHEDs in Parkinso’s Disease Models
4.4. Application of DPSCs in Other Neurodegenerative Disorders
Pathology | Pre-Clinical Model | DPSC Administration | Outcome | References |
---|---|---|---|---|
Alzheimer’s Disease | Primary rat hippocampal cultures treated with Amyloid-β 1–42 (5–10 µM) or 6-OHDA (5–40 µM) for 24 h | Co-culture with primary neurons | Rescue of cell viability; increase in expression of neuronal markers: release of neurotrophins | [69] |
Human neuroblastoma SH-SY5Y cells treated with 20 nmol/L Okadaic Acid for 24 h | Transwell insert with porous membrane | Restoration of morphology and cell viability; reduction in apoptosis; reduction in phospho-Tau | [70] | |
Human neuroblastoma SH-SY5Y cells treated with 5 µM Amyloid-β 1–42 | Transplantation of DPSCs secretome | Increased cell viability; up-regulation of anti-apoptotic Bcl-2; down-regulation of pro-apoptotic Bax | [49] | |
Mice treated with Kainic Acid | Intrahippocampal transplantation of DPSCs or their secretome | Reduction in cognitive impairment; improved memory acquisition; reduction in neuroinflammation; increase in neurogenesis | [74] | |
Rats treated with 1 mg/mL Amyloid-β 1–42 | Intrahippocampal transplantation of DPSCs | Increased secretion of neurotrophins; improved cognitive behavior | [75] | |
Parkinson’s Disease | Rats intraperitoneally injected with 20 mg/kg MPTP | Intranasal | Increased senosory-motor coordination; rescue of olfactory functions; increase in TH-positive neurons | [85] |
Rats injected unilaterally in the striatum with 10 µg/µL 6-OHDA | Injection of SHEDs in the striatum | Recovery of neurological behavior; increased survival; increase in TH-positive neurons | [87] | |
Cerebellar Ataxia | Rats injected intraperitoneally with 75 mg/kg 3-Acetylpyridine | Intracerebellar injection | Enhanced motor skills; enhanced muscle activity; rescue of cerebelar volume; reduction in inflammatory cytokines | [88] |
Vascular Dementia | Two-bessel occlusion in rats | Injection of marked murine DPSCs into tail veins | Successful migration of DPSCs into the lesioned areas observed by PKH compounds; increased neuronal markers; improved behavioral performances | [90] |
Huntington’s Disease | Rats injected intraperitoneally with 30 mg/kg of 3-nitropropionic acid | Bilateral transplantation of marked DPSCs | Improved motor skills and muscle activity; increased neurite length; reduced astrogliosis and microgliosis; downregulation of Caspase-3 activity; decreased expression of inflammatory cytokines. | [93] |
Rats injected intraperitoneally with 20 mg/kg of 3-nitropropionic acid | Intravenous injection of SHEDs | SHEDs can cross the BBB; increased expression of neurotrophins; | [95] | |
Amyotrophic Lateral Sclerosis | Tg-SOD1G93A mouse model | Transplantation of DPSCs secretome | Reduced neuromuscular junction denervation; reduced muscle atrophy; reduced neuronal loss; extended lifespan. | [96] |
5. DPSCs- and SHEDs-Based Clinical Trials for Neuropathological Disorders
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Type and Source of Stem Cells | Medium for Neuronal Lineage | Neuronal Markers | Neuronal Sub-Population | References |
---|---|---|---|---|
Adult DPSCs from third molar | Neurobasal + 2% B27 + 2 mM Gln + 20 ng/mL basic FGF + 20 ng/mL EGF | β3-Tubulin; PLCγ activity | Pan-neuronal | [43] |
Adult DPSCs from third molar | DMEM/F12 (1:1) + 2.5% FCS + 10 μM 5-azacytidine + 10 ng/mL basic FGF. After 48 h: 250 μM IBMX + 50 μM forskolin + 200 nM TPA + 1 mM dbcAMP + 10 ng/mL bFGF + 10 ng/mL NGF + 30 ng/mL NT-3 + 1% of insulin-transferrin-sodium selenite premix. | N-tub; NeuN; Neurofilament-M. Electrical activity | Pan-neuronal | [44] |
Adult DPSCs from premolar teeth | Neuronal medium + N2 + 20 ng/mL EGF + 20 ng/mL FGF; PIN1 inhibitor (juglone) or PIN1 overepression (through adenovirus) | NeurN; Nestin; VGluT1; GABA; TH | Pan-neuronal; GABAergic; Glutamatergic | [45] |
SHEDs from deciduous baby teeth; DPSCs from adult third molar | Neurobasal + 0.5% B27 + 200 ng/mL SHH + 100 ng/mL FGF8 + 50 ng/mL basic FGF + BDNF for 72 h | Nurr1; Engrailed1; Pitx3; Nestin; β3-Tubulin; TH; Ca2+ influx | Dopaminergic Neurons | [46] |
Adult DPSCs from third molar | For cholinergic neurons: DMEM:F12 (1:1) + 1% N2 + 1% non-essential aminoacids + 0.2% Heparin + 0.1 µM RA. After 96 hours: + 100 ng/mL SHH. After 48 h: + 1 µM cAMP 200 ng/mL ascorbic acid. After 72 h: + 10 ng/mL BDNF + 10 ng/mL GDNF + 10 ng/mL IGF-1. For dopaminergic neurons: DMEM:F12 (1:1) + 1% N2 + 300 ng/mL Noggin. After 96 h: + 50 ng/mL BDNF + 200 mM Ascorbic acid + 50 µg/mL SHH + 50 µg/mL FGF8b. After 120 h:—bFGF After 72 h: + 10 ng/mL GDNF + 2 µg/mL TGF-βIII + 200 mM cAMP. | Nestin; β3-Tubulin; NeuN; TH; Choline AcetylTransferase | Dopaminergic and Cholinergic Neurons | [47] |
Adult DPSCs from third molar | DMEM:F12 (1:1) + 5% FBS + 10 µM non-essential amino acids + 2 mM Glutamatec+ 10 mM RA + 50 µM Ascorbic Acid + 5 µM Insulin + 10 nM Dexamethasone + 20 nM Progesterone + 20 nM Estradiol + 50 ng/mL NGF + 10 ng/mL Thyroxine | Nestin; β3-Tubulin; Brn-3a; TRPV1; substance-P; Ca2+ imaging | Peripheral neuronal cells (pain receptors) | [48] |
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Candelise, N.; Santilli, F.; Fabrizi, J.; Caissutti, D.; Spinello, Z.; Moliterni, C.; Lancia, L.; Delle Monache, S.; Mattei, V.; Misasi, R. The Importance of Stem Cells Isolated from Human Dental Pulp and Exfoliated Deciduous Teeth as Therapeutic Approach in Nervous System Pathologies. Cells 2023, 12, 1686. https://doi.org/10.3390/cells12131686
Candelise N, Santilli F, Fabrizi J, Caissutti D, Spinello Z, Moliterni C, Lancia L, Delle Monache S, Mattei V, Misasi R. The Importance of Stem Cells Isolated from Human Dental Pulp and Exfoliated Deciduous Teeth as Therapeutic Approach in Nervous System Pathologies. Cells. 2023; 12(13):1686. https://doi.org/10.3390/cells12131686
Chicago/Turabian StyleCandelise, Niccolò, Francesca Santilli, Jessica Fabrizi, Daniela Caissutti, Zaira Spinello, Camilla Moliterni, Loreto Lancia, Simona Delle Monache, Vincenzo Mattei, and Roberta Misasi. 2023. "The Importance of Stem Cells Isolated from Human Dental Pulp and Exfoliated Deciduous Teeth as Therapeutic Approach in Nervous System Pathologies" Cells 12, no. 13: 1686. https://doi.org/10.3390/cells12131686