# Potential Effects of Photobiomodulation Therapy on Human Dental Pulp Stem Cells
## 1 Introduction  
The use of mesenchymal stem cells (MSCs) to replace conventional therapeutic regimes in tissue engineering and regenerative medicine has been the subject of growing interest in the medical and dental fields [1]. Regenerative medicine has been focusing on directing the differentiation of stem cells into lineage-specific, functional cells that can promote tissue repair and organization [2]. With the advent of modern tissue engineering concepts and the discovery of dental stem cells, stem cell therapy and pulp tissue regeneration have been evolving for years to replace the shortcomings of dental materials and the pitfalls of traditional therapeutic approaches in dentistry [3]. Mesenchymal stem cells (MSCs) are multipotent cells that can be derived from various tissues including bone marrow, dental pulp, adipose tissue, and umbilical cord, to name a few. These cells possess the ability to self-renew and differentiate into multiple cell types depending on the specific in vitro conditions provided [4]. Dental pulp stem cells (DPSCs) are an excellent source for pulp regeneration [5]. It was demonstrated in the literature that different types of extracellular matrix (ECM) scaffolds--with and without growth factors--can induce the odontogenic differentiation of DPSCs [5, 6]. Enamel, whichis the only mineralized tooth tissue derived from the dental epithelium, does not have any regenerative capabilities. However, the other mineralized periodontal and dental tissues, including dentin, pulp, cementum, periodontal ligament, and alveolar bone, are formed from neural crest-derived dental ectomesenchyme and have varying degrees of regenerative capability. This capability is believed to be partially due to the presence of stem cells [7]. All dental tissues are subject to traumatic injuries and caries infection [3]. Current clinical dentistry focuses on restorative and endodontic therapies that have several limitations based on eventual biomaterial failure [2; 8]. Therefore, dental bioengineering research has focused extensively on pulp regeneration and dentinogenesis to understand and clinically promote the formation and mineralization of the pulp-dentin complex [9]. The reparative capacity for dentin has important implications, especially with the current emphasis on minimally invasive conservative interventional strategies. However, the progress in these bioengineering approaches in vitro has not been actively implemented into clinical practice. One of the major novel technologies capable of modulating stem cell proliferation and differentiation with potent clinical implications in dentistry is laser photobiomodulation (PBM). Lasers have been popular in clinical dentistry and can be used for both surgical and non-surgical applications based on the power used. High-power lasers involve using high power levels to vaporize or ablate tissues, promote blood coagulation to stop bleeding, and disinfect tissues, primarily relying on the photothermal effects [10]. In contrast, lasers at low power involve using electromagnetic or photochemical processes to achieve therapeutic benefits without causing cellular damage or death [11]. Using the appropriate dose, low-power lasers have been noted to stimulate biological cells to invoke physiological responses to improve local blood circulation, regulate cell functions, and promote immunological functions, wound healing, hair growth, and tissue regeneration while reducing pain and inflammation [4; 10; 11]. The role of PBM therapy in dental and oral tissue regeneration is gaining much attention as a non-invasive biophysical modality when used in conjunction with growth factors and scaffolds [2; 4; 8]. Despite their popular clinical usage, there is surprisingly little information on the precise biological responses and safety of PBM parameters, potentially contributing to the inconsistencies in its clinical efficacy [11].