Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair
Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair
Lihua Luo,1 Yan He,1,2 Xiaoyan Wang,1 Brian Key,3 Bae Hoon Lee,4,5,6 Huaqiong Li,4,5,6 and Qingsong Ye1,2
1WMU-UQ Group for Regenerative Medicine, Institute of Stem Cells and Tissue Engineering, School of Stomatology, Wenzhou Medical University, Wenzhou 325035, China
2School of Dentistry, The University of Queensland, Herston, QLD 4006, Australia
3School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia
4School of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325035, China
5Wenzhou Institute of Biomaterials and Engineering, CAS, Wenzhou 325011, China
6Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute of Biomaterials and Engineering, CAS, Wenzhou 325011, China
Correspondence should be addressed to Huaqiong Li; nc.ca.ebiw@qhil and Qingsong Ye; moc.liamtoh@eygnosgniq
Received 7 November 2017; Accepted 22 March 2018; Published 7 May 2018
Academic Editor: Tao-Sheng Li
Copyright © 2018 Lihua Luo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases.
1. Introduction
Traumatic events, iatrogenic injuries, and neurodegenerative diseases can lead to axonal degeneration, inflammation, neuron death, and cytoarchitectural malformation in both the peripheral nervous system (PNS) and central nervous system (CNS) [1–6]. Conventional medical therapies have limited efficacy in supporting functional recovery from nervous damage since the mature nervous system lacks the necessary precursor cells to generate new neurons and glial cells [7]. Recently, stem cell-based strategies in combination with novel technologies (e.g., precisely controlled hydrogels) have heralded potential new therapeutic approaches for addressing nerve regeneration and repair [8–11].
Mesenchymal stem cells (MSCs) harvested from adult tissues are potentially an important therapeutic cell source for treatment of CNS and PNS perturbations since they possess the capacity for both neuronal and glial differentiation. MSCs also express numerous anti-inflammatory and neurotrophic factors supporting nerve repair [8–14]. These multipotent stem cells are present in bone marrow [15, 16], adipose tissue [17, 18], umbilical cord [19, 20], and dental tissue [21–25]. Dental pulp stem cells (DPSCs) can readily be obtained from the third molars, usually discarded as medical waste. DPSCs have MSC-like characteristics such as the ability for self-renewal and multilineage differentiation. These dental pulp-derived MSCs avoid ethical concerns when sourced from other tissue, and they can be obtained without unnecessary invasive procedures, for example, MSCs collected from bone marrow or adipose tissue [9, 26–28]. DPSCs can differentiate into neuron-like cells and secrete neurotrophic factors such as neurotrophin (NT) [29, 30]. In addition, DPSCs express neuron-related markers even before being induced to neuronal differentiation [29, 31, 32]. Taken together, these unique properties make DPSCs an excellent candidate for stem cell-related therapies in nerve diseases.
2. Dental Pulp Stem Cells (DPSCs)2.1. The Characteristics of DPSCs
The basic tooth structure consists (...truncated)