Towards a New Concept of Regenerative Endodontics Based on Mesenchymal Stem Cell-Derived Secretomes Products

Abstract

The teeth, made up of hard and soft tissues, represent complex functioning structures of the oral cavity, which are frequently affected by processes that cause structural damage that can lead to their loss. Currently, replacement therapy such as endodontics or implants, restore structural defects but do not perform any biological function, such as restoring blood and nerve supplies. In the search for alternatives to regenerate the dental pulp, two alternative regenerative endodontic procedures (REP) have been proposed: (I) cell-free REP (based in revascularization and homing induction to remaining dental pulp stem cells (DPSC) and even stem cells from apical papilla (SCAP) and (II) cell-based REP (with exogenous cell transplantation). Regarding the last topic, we show several limitations with these procedures and therefore, we propose a novel regenerative approach in order to revitalize the pulp and thus restore homeostatic functions to the dentin-pulp complex. Due to their multifactorial biological effects, the use of mesenchymal stem cells (MSC)-derived secretome from non-dental sources could be considered as inducers of DPSC and SCAP to completely regenerate the dental pulp. In partial pulp damage, appropriate stimulate DPSC by MSC-derived secretome could contribute to formation and also to restore the vasculature and nerves of the dental pulp.

Towards the Standardization of Mesenchymal Stem Cell Secretome-Derived Product Manufacturing for Tissue Regeneration

“…Sci. 2023, 24, x FOR PEER REVIEW 8 of 15 [108,109]. The various steps of centrifugation are required to remove these apoptotic bodies.…”

“…These elements include proteins and extracellular vesicles. These extracellular vesicles can contain apoptotic bodies, which appear during the programmed cell death process [ 108 , 109 ]. The various steps of centrifugation are required to remove these apoptotic bodies.…”

“…The use of such cell-free therapy in regenerative medicine has several advantages over stem-cell-based applications: safety considerations, control of protein content, storage without toxic cryopreservative agents, economical and practical aspects, and the possibility to orientate CM potential by preconditioning [ 108 ]. This cell-free approach will guide and promote revascularization and endogenous cell homing [ 109 ], with the possibility to specifically orientate tissue regeneration [ 116 ]. The use of MSC-CM is locally applied to reproduce stem cells’ intercellular signaling, in order to reproduce the biological effects of the original cells [ 117 ].…”

Exploring Various Transfection Approaches and Their Applications in Studying the Regenerative Potential of Dental Pulp Stem Cells

“…Studies have shown similarities between DPSCs and bone marrow stromal cells, which improve the application of DPSCs in musculoskeletal regenerative medicine [15]. These cells are also targeted in research as a source of autologous cells, which are of great interest in the field of regenerative medicine, both inside and outside the oral cavity [18]. Table 1 summarizes the key properties of DPSCs.…”

Advancing Dentistry through Bioprinting: Personalization of Oral Tissues

“…A summary of the proposal for a cell-free approach to dental pulp regeneration using MSC-derived CM/EV: (A) The treatment sequence for immature permanent teeth with pulp necrosis is outlined; (B) The regenerative procedure for cases with partially damaged pulp is summarized. Key components involved include: MTA (mineral trioxide aggregate), SCAP (stem cells from apical papilla), EDTA (ethylenediaminetetraacetic acid)[53].…”