Role of Angiogenesis in Endodontics: Contributions of Stem Cells and Proangiogenic and Antiangiogenic Factors to Dental Pulp Regeneration

Abstract

Introduction Dental pulp regeneration is a part of regenerative endodontics, which includes isolation, propagation, and re-transplantation of stem cells inside the prepared root canal space. The formation of new blood vessels through angiogenesis is mandatory to increase the survival rate of re-transplanted tissues. Angiogenesis is defined as the formation of new blood vessels from preexisting capillaries, which has great importance in pulp regeneration and homeostasis. Here the contribution of human dental pulp stem cells and proangiogenic and antiangiogenic factors to angiogenesis process and regeneration of dental pulp is reviewed. Methods A search was performed on the role of angiogenesis in dental pulp regeneration from January 2005 through April 2014. The recent aspects of the relationship between angiogenesis, human dental pulp stem cells, and proangiogenic and antiangiogenic factors in regeneration of dental pulp were assessed. Results Many studies have indicated an intimate relationship between angiogenesis and dental pulp regeneration. The contribution of stem cells and mechanical and chemical factors to dental pulp regeneration has been previously discussed. Conclusions Angiogenesis is an indispensable process during dental pulp regeneration. The survival of inflamed vital pulp and engineered transplanted pulp tissue are closely linked to the process of angiogenesis at sites of application. However, the detailed regulatory mechanisms involved in initiation and progression of angiogenesis in pulp tissue require investigation.

Effect of biomaterials on angiogenesis during vital pulp therapy

“…This issue was also raised by Tziafas et al 27) besides the traditional criteria such as easy handling, infection control, good sealing ability, and exploiting endogenous signaling for dentinal bridge formation. These authors also mentioned the use of exogenous signaling molecules in new pulp capping strategies 9) .…”

“…The challenge, however, is to create pulp tissue in a vacant canal, which is exactly identical to the pulpal tissue before necrosis and can function properly 8,9) . This issue is one of the main differences between regenerative attempts and the conventional treatments including apexification.…”

“…In dentin-pulp complex regeneration, clinicians attempt to provide an effective pulp capping with appropriate sealing ability 5) , and maintain the vitality of irritated pulp tissues and promote the formation of a dentinal bridge 8–10) and other tissues including neural cells 11) . In these procedures, the progenitor dental pulp stem cells (DPSCs) are migrated, recruited, and differentiated into odontoblast-like cells, which have the ability to produce reparative dentin 9,12) . Although, this issue seems very simple in theory, in reality the whole process is possible if the homeostasis of pulp is reestablished 8) .…”

“…In addition, angiogenesis has a pivotal role in dentinal and dental pulp tissues’ regenerative and reparative procedures 1,9) . The present study attempts to review the effects of dental materials and treatment modalities used in dentin-pulp complex and dental pulp regeneration on angiogenesis.…”

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

“…The endothelial shift of MSCs in these studies is mainly indicated by the upregulation of typical endothelial cell (EC) markers, such as PECAM-1, VEGFR-2, vWF, and VE-cadherin and further evidenced by functional assays, such as ability to form capillary-like structures on Matrigel or other matrices or by uptake of Acetylated-Low Density LipoProtein Lipase (Ac-LPL), but also by various in vivo assays, including mouse Matrigel assays and Chicken Chorioallantoic Membrane (CAM) assays [33, 34, 122]. …”