Periodontal ligament stem cells as a promising therapeutic target for neural damage

 Just why was this research needed? There has been research on dental pulp stem cells since October 2011. Are your mentors and senior researchers that incompetent about not knowing previous research?  With a decent database of stroke research and protocols this problem wouldn't occur. But since we have fucking failures of stroke associations  no one is going to solve the database problem.

• dental pulp (6 posts to October 2011)

Periodontal ligament stem cells as a promising therapeutic target for neural damage

• Fariba Mohebichamkhorami,
• Roya Fattahi,
• Zahra Niknam,
• Morteza Aliashrafi,
• Sahar Khakpour Naeimi,
• Samira Gilanchi &
• Hakimeh Zali 

Stem Cell Research & Therapy volume 13, Article number: 273 (2022) Cite this article

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Abstract

Background

The damaged neuronal cells of adult mammalian lack the regenerative ability to replace the neuronal connections. Periodontal ligament stem cells (PDLSCs) are the promising source for neuroregenerative applications that can improve the injured microenvironment of the damaged neural system. They provide neuronal progenitors and neurotrophic, anti-apoptotic and anti-inflammatory factors. In this study, we aimed to comprehensively explore the various neuronal differentiation potentials of PDLSCs for application in neural regeneration therapy.

Main text

PDLSCs have superior potential to differentiate into various neural-like cells through a dedifferentiation stage followed by differentiation process without need for cell division. Diverse combination of nutritional factors can be used to induce the PDLSCs toward neural lineage. PDLSCs when coupled with biomaterials could have significant implications for neural tissue repair. PDLSCs can be a new clinical research target for Alzheimer's disease treatment, multiple sclerosis and cerebral ischemia. Moreover, PDLSCs have beneficial effects on retinal ganglion cell regeneration and photoreceptor survival. PDLSCs can be a great source for the repair of injured peripheral nerve through the expression of several neural growth factors and differentiation into Schwann cells.

Conclusion

In conclusion, these cells are an appealing source for utilizing in clinical treatment of the neuropathological disorders. Although significant in vitro and in vivo investigations were carried out in order for neural differentiation evaluation of these cells into diverse types of neurons, more preclinical and clinical studies are needed to elucidate their therapeutic potential for neural diseases.

Introduction

The central nervous system (CNS) and the peripheral nervous system (PNS) are parts of the nervous system. The brain and spinal cord make up the CNS, whereas cranial and spinal nerves, as well as their associated ganglia, constitute the PNS. The PNS has a built-in ability to regenerate and repair itself, whereas the CNS is essentially incapable of self-repair. Furthermore, depending on the characteristics and type of damage, the inherent regenerating ability is limited through injury itself [1].

In neural injuries, the damaged neural cells such as neurons and glial cells of adult mammalian lack the regenerative ability to replace the neuronal connections. This is due to the limited ability of neuronal progenitors to regenerate functional neuronal cells and inhibition of neural regeneration by the local injured microenvironment, especially in the glial scar [2].

One of the main formidable reasons for the limited success of pharmacotherapeutic strategies in neural damages is the microenvironment of the injury site with many molecular growth inhibitors that are hostile to any neuroregenerative therapy and function restoring of nerve fibers. It leads to the incapability of the damaged nerves to regrow and develop new synaptic connections. Targeting these inhibitors could be an efficient approach to overcome the permanent stopping of nerve growth [3].

The development of more precise therapies focused at specific molecular targets linked with a specific disease or injury of the nervous system has resulted from advances in neuroregenerative research. Due to several pathological injury processes and mechanisms, any neuroregenerative approach that focuses on just one of the events or mechanisms will not probably lead to a considerable therapeutic effect on neural injuries. The reasons for the limited therapeutic options are mainly because of both the extracellular and intracellular components of the nervous system that inhibits regeneration. To bridge the short-term requirements and revive immediate function of the nervous system, changes in plasticity and neuroregeneration firstly occur at the regional level. The lengthy and more permanent process of restoring function occurs at cellular level and promotes one or more of the restorative mechanisms which may improve neurological damages [4, 5].

Neuroregenerative medicine (NRM) is a growing field with the goal of neurogenesis, angiogenesis and synaptic plasticity [5] through replacement of lost cells and tissues and restoration of normal function [2]. Scientists are optimistic about the potentials of NRM to lead to providing novel approaches for the treatment of neural diseases and answer the ethical questions about their clinical applications [6].

NRM uses stem cells as a promising tool that make up for the scarcity of cell alternatives. Transplanted stem cells can improve the microenvironment in the injured site of the neural system and provide neuronal progenitors [7]; then, they help to slow or repair the deterioration related to degenerative or traumatic neural diseases and trigger a great effort in the field of preclinical and clinical neural research [8].

Mesenchymal stem cells (MSCs) have potential to integrate into host neuronal networks and renew functional neural connections. They can restore synaptic transmitter secretion, modulate the plasticity of damaged host tissues as well as release growth and neurotrophic factors with ability to promote cell survival [9]. In addition, MSCs have been found to diminish inflammation in vivo by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokines and antigen-specific T-regulatory cells [10]. Researchers suggested that MSCs can cross the blood–brain barrier (BBB) [11], and this ability is the main reason for the treatment potential in neural diseases like cerebral ischemic diseases or spinal cord injuries [12, 13].

The oral cavity as an available source of MSCs includes two kinds of cells. Nondental oral MSCs which comprise periodontal ligament stem cells (PDLSCs), gingival MSCs (GMSCs), and dental follicle stem cells (DFSC) and the dental MSCs which consist of stem cells from apical papilla (SCAP), dental pulp stem cells (DPSCs) and stem cells from exfoliated deciduous teeth (SHED) [7].

Oral stem cells are rather accessible and show broad differentiation potential and high plasticity; hence, they can make autologous cell transplantation possible [8]. Moreover, they have advantages such as a higher proliferation rate and potential of immunosuppression [14, 15]; therefore, they are an excellent cell source in order for allogeneic transplantation.

They originate from cranial neural crest-derived ectomesenchymal cells (CNCCs); thus, they are capable of differentiation into neural cells in order for the reconstruction of central nervous system tissues. These cells express neural progenitors markers, including nestin, Pax6, Tuj1 and p75/NGFR, and have a more favorable neurotrophic secretome [16].

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