Intraventricular Injection of Human Dental Pulp Stem Cells Improves Hypoxic-Ischemic Brain Damage in Neonatal Rats

Abstract

ObjectiveTo investigate the effect of intraventricular injection of human dental pulp stem cells (DPSCs) on hypoxic-ischemic brain damage (HIBD) in neonatal rats.MethodsThirty-six neonatal rats (postnatal day 7) were assigned to control, HIBD, or HIBD+DPSC groups (n = 12 each group). For induction of HIBD, rats underwent left carotid artery ligation and were exposed to 8% to 10% oxygen for 2 h. Hoechst 33324-labeled human DPSCs were injected into the left lateral ventricle 3 days after HIBD. Behavioral assays were performed to assess hypoxic-ischemic encephalopathy (HIE), and on postnatal day 45, DPSC survival was assessed and expression of neural and glial markers was evaluated by immunohistochemistry and Western blot.ResultsThe HIBD group showed significant deficiencies compared to control on T-maze, radial water maze, and postural reflex tests, and the HIBD+DPSC group showed significant improvement on all behavioral tests. On postnatal day 45, Hoechst 33324-labeled DPSC nuclei were visible in the injected region and left cortex. Subsets of DPSCs showed immunostaining for neuronal (neuron-specific enolase [NSE], Nestin) and glial markers (glial fibrillary acidic protein [GFAP], O4). Significantly decreased staining/expression for NSE, GFAP, and O4 was found in the HBID group compared to control, and this was significantly increased in the HBID+DPSC group.ConclusionIntraventricular injection of human DPSCs improves HIBD in neonatal rats.

Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair

“…The fact that the majority of DPSC‐derived cells were rapidly cleared despite the improvement in function corroborates the theory that DPSC promote functional regeneration of endogenous CNS tissue. In another report, DPSC transplanted into the ventricles of animals with hypoxic‐ischaemic brain damage promoted the survival and formation of neuronal and glial cells while improving functional performance as assessed by a variety of behavioural tests . Although these results implied that that DPSC may have formed new cells to replace the damaged neurons, considering the low survival rate of the grafted cells, it is plausible to assume that the achieved neuroprotection was due to indirect endogenous stimulation and protection of host neurons and glia .…”

“…In another report, DPSC transplanted into the ventricles of animals with hypoxic‐ischaemic brain damage promoted the survival and formation of neuronal and glial cells while improving functional performance as assessed by a variety of behavioural tests . Although these results implied that that DPSC may have formed new cells to replace the damaged neurons, considering the low survival rate of the grafted cells, it is plausible to assume that the achieved neuroprotection was due to indirect endogenous stimulation and protection of host neurons and glia . Using SHED cells in a model of hypoxic‐ischaemic injury of the brain in mice, it was found that SHED transplantation improved neurological function as measured by behavioural foot‐fault testing whilst preventing tissue atrophy and reducing the number of endogenous apoptotic cells .…”

Review and Outlook of Stem Cell Transplantation for Neonatal Hypoxic- Ischemic Encephalopathy

“…Recently, some scholars study that human DPSCs are transplanted into neonatal HIE animal model, the result show that human DPSCs may reduce the brain injury of mice HIE, inhibition of proinflammatory cytokines and cell apoptosis [42]; Also find that DPSCs may an directly differentiate into neurons or glial cells, promote the proliferation of host stem cell and differentiation into neurons or glial cells, meanwhile, human DPSCs also may improve the neural behavior of animal [43]. DPSCs as a new member of stem cells, it will play an key role for nerve injury disease.…”

Cryopreservation and Banking of Dental Stem Cells

“…DSCs have gained great interest during the last decade because of their accessibility, (trans)differentiation potential and high proliferative capacity. Elaborate preclinical research has highlighted the underlying biological and cellular properties of different DSCs, as well as their potential application in the treatment of medical conditions [92][93][94][95][96][97], such as myocardial infarction [98], ischemic disease [99], nerve injury and other neurodegenerative disorders [70,47,[100][101][102][103][104][105]50], inflammatory diseases [106,107], diabetes [108][109][110][111][112], muscular dystrophy [113,26,114], bone/cartilage defects [115][116][117][118][119], hair follicle loss [120], skin injuries [121], salivary gland defects [122], corneal epithelial defects [123][124][125][126], and the regeneration of dental tissues [127][128][129][130]…”