Dental Stem Cells in Pulp Regeneration: Near Future or Long Road Ahead?

Abstract

Although regenerative endodontic procedures have yielded an impressive body of favorable outcomes, the treatment of necrotic immature permanent teeth in particular remains to be a challenge. Recent advances in dental stem cell (DSC) research have gained increasing insight in their regenerative potential and prospective use in the formation of viable dental tissues. Numerous studies have already reported successful dental pulp regeneration following application of dental pulp stem cells, stem cells from the apical papilla, or dental follicle precursor cells in different in vivo models. Next to responsive cells, dental tissue engineering also requires the support of an appropriate scaffold material, ranging from naturally occurring polymers to treated dentin matrix components. However, the routine use and banking of DSCs still holds some major challenges, such as culture-associated differences, patient-related variability, and the effects of culture medium additives. Only in-depth evaluation of these problems and the implementation of standardized models and protocols will effectively lead to better alternatives for patients who no longer benefit from current treatment protocols.

Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

“…For example, the changes shown might be beneficial for site-specific application depending on the target tissues but adverse for systemic administration or vice versa. Since development of adequate numbers of high quality SCs at early passages is a prerequisite for any safe cell therapy treatment, considerable effort has been put into evaluating the consequences of the cultivation process on stem cell behavior, in particular, in developing reliable standardization protocols in the form of Standard Operating Procedures (SOPs) to be routinely applied to characterize (1) phenotypic and genetic stability of cultured dental MSCs, (2) efficacy in regenerating target tissues, (3) the permitted population doubling before senescence becomes a problem, (4) the absence of microbial, viral, fungal, mycoplasma, endotoxin, or other contamination in cultured cells, and (5) lack of tumorigenicity, toxicity, and immunogenicity, something highlighted in recent reports discussing current challenges towards clinical application of dental MSCs [168, 169]. It becomes clear from these reports that the lack of reliable characterization methods and reference standards for the evaluation of each of the above mentioned important parameters presents a major hurdle for the development of cGMP-grade cells and respective CBMPs.…”

Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells

“…Dental stem cells can be harvested from several dental sources, including DPSCs, stem cells from human exfoliated deciduous teeth (SHED), stem cells from the apical papilla (SCAP), periodontal ligament stem cells (PDLSC), and dental follicle precursor cells (DFSC)27. In particular, DPSCs are a potential alternative source for bone regeneration/healing and tissue engineering attributable to their high proliferation rates, their extended differentiation potential, and paracrine properties282930. In addition, similarly to MSCs that have been shown to exhibit immunomodulatory properties in syngeneic, allogeneic and xenogeneic applications31, human DPSC transplanted into large rat calvarial defects have been demonstrated to differentiate into osteogenic cells without any graft rejection32.…”

The extracts of bredigite bioceramics enhanced the pluripotency of human dental pulp cells

“…hDPCs were easily obtained from extracted teeth and possess an outstanding capacity to differentiate into multiple cell lineages, including odontoblasts and osteoblasts . In particular, hDPCs are regarded as a good choice for the regeneration of different tissues and organs, with a special emphasis on alveolar bones, periodontal tissue, and teeth . However, extended in vitro culture using current methodologies is known to cause loss of hDPCs' regenerative capacity .…”

“…24 In particular, hDPCs are regarded as a good choice for the regeneration of different tissues and organs, with a special emphasis on alveolar bones, periodontal tissue, and teeth. 25 However, extended in vitro culture using current methodologies is known to cause loss of hDPCs' regenerative capacity. 26 Stro1 is an early marker of stem cells, and its expression decreased at later passages.…”