fibrin (PRF) is an autologous product that contains high concentrations of nonactivated, functional intact platelets within a fibrin matrix that release a relatively constant concentration of growth factors/cytokines over a few days. It is easier to produce but it has to be used immediately after blood drawing and centrifugation. PRF is a potential substitute for PRP in regenerative endodontics and other regenerative procedures involving reconstruction of hard tissues, such as surgical endodontics and adjunctive surgical procedures like root amputation, hemisection, and repair of root perforations.
The main purpose of PRF Applications in Endodontics is to stimulate research in regenerative procedures in endodontics and encourage clinicians to use PRF to improve healing of their patients and save natural dentition. The book has seven chapters and starts with the history of stem cells in regenerative medicine and its possible applications in endodontics, followed by PRF armamentarium and description of how to make PRF, use of PRF in nonsurgical endodontic procedures, its soft tissue applications, hard tissue applications, surgical endodontics, and finally socket preservation. It is assembled by well-known scientists and clinicians who are experts in their fields and interested in the use of innovative materials and techniques to improve human lives.
Mahmoud Torabinejad, DMD, MSD, PhD
References
1 Banchs F, Trope M. Revascularization of immature permanent teeth with apical periodontitis: New treatment protocol? J Endod 2004;30:196–200.
2 Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part I: Technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:e37–e44.
3 Iwaya SI, Ikawa M, Kubota M. Revascularization of an immature permanent tooth with apical periodontitis and sinus tract. Dent Traumatol 2001;17:185–187.
4 Mao JJ, Kim SG, Zhou J, et al. Regenerative endodontics: Barriers and strategies for clinical translation. Dent Clin North Am 2012;56:639–649.
5 Nevins A, Wrobel W, Valachovic R, Finkelstein F. Hard tissue induction into pulpless open-apex teeth using collagen-calcium phosphate gel. J Endod 1977;3:431–433.
6 Nygaard-Ostby B, Hjortdal O. Tissue formation in the root canal following pulp removal. Scand J Dent Res 1971;79:333–349.
7 Rule DC, Winter GB. Root growth and apical repair subsequent to pulpal necrosis in children. Br Dent J 1966;120:586–590.
8 Torabinejad M, Faras H. A clinical and histological report of a tooth with an open apex treated with regenerative endodontics using platelet-rich plasma. J Endod 2011;38:864–868.
9 Torabinejad M, Turman M. Revitalization of tooth with necrotic pulp and open apex by using platelet-rich plasma: A case report. J Endod 2011;37:265–268.
Stem Cells in Regenerative Medicine
LEARNING OBJECTIVES
• Gain a better understanding of stem cell biology and how it relates to regenerative medicine, specifically dentistry
• Compare different sources of stem cells and the relative strengths and weaknesses associated with each source
• Gain a better understanding of a mesenchymal stem cell secretome and why it is important therapeutically
Regenerative medicine, also commonly known as tissue engineering, is a discipline of medicine that is focused on restoring native tissue structure and functionality to an afflicted tissue. Dentistry has traditionally been at the forefront of regenerative medicine, commonly employing novel bioactive materials to stimulate bone growth and regeneration. Recently, stem cells and other cell-based therapies have attracted significant attention in this space due to their ability to not only treat patients’ symptoms but to improve physiologic activity and restore native tissue structure.
Stem cells are characterized by a capacity for self-renewal while maintaining an undifferentiated state and, given the proper stimulus, the ability to differentiate into various types of specialized somatic cells. Stem cells are further classified by their relative differentiation potential. Stem cells that can differentiate into any cell type in the body are termed totipotent and have the widest differentiation potential. Mesenchymal stem cells (MSCs) are multipotent stem cells that are most closely associated with the mesodermal lineage and are known to differentiate into chondrogenic, osteogenic, myogenic, and adipogenic cell types.1
The discovery of stem cells and their multipotent potential has encouraged the development of the whole field of research, projected to have reached $170 billion by 2020. In particular, the multipotent MSCs, with their stem-like quality to differentiate into mesodermal cell types, have been a focus. Indeed, overall revenue for MSC products was projected to be $10.9 billion from 2010 to 2020.Alongside the possibilities of therapeutic successes (ranging from treating graft-versus-host disease, Crohn disease, spinal cord injury, and use in support of hematopoietic stem cell treatments) comes the inherent ethical and logistic dilemmas behind obtaining stem cells. This chapter focuses on MSCs due to their popularity for regenerative applications.
Mesenchymal Stem Cells
Stem cell sources
First isolated in bone marrow, bone marrow–derived MSCs were found to be precursors to multiple cell types and could be viably cultured while retaining their capacity for multilineage differentiation. Obtained from an invasive bone marrow harvesting procedure, bone marrow–derived MSCs avoid the ethical concerns as well as tumorigenicity of embryonic stem cells and have subsequently been used in a nearly exponential increase in research studies and trials.2 Unfortunately, bone marrow–derived MSCs are relatively low yield and limited to autologous use, requiring in vitro expansion that increases the risk of contamination. Additionally, harvesting the cells requires a surgical procedure with associated donor morbidity and risk, and the potency (ie, “stemness”) has been questioned when compared with more recently discovered sources of MSCs.3
One of these sources is umbilical cord blood (also known as cord blood), collected via venipuncture of the typically discarded umbilical cord. Painless and without morbidity, cord blood is considered superior to human bone marrow stem cells in its harvesting and yield. Cord blood is cryopreserved in two main methods using dimethyl sulfoxide (DMSO): (1) red cell reduction, which is less expensive to store and easier to defrost; and (2) plasma depletion, which is more economical to process. Public cord blood banks cost about $1,500 to $2,500 per unit stored, while private banks typically charge an initial processing fee of $1,400 to $2,300 plus annual storage costs of $115 to $150. However, MSCs only represent a small proportion—1,000 to 5,000 MSCs in one 100-mL unit of cord blood—of the cell types within cord blood, which includes hematopoietic cell types, endothelial and progenitor cells, as well as MSCs.4
There has also been recent attention toward Wharton’s jelly (WJ) within umbilical cords. WJ was found at the turn of the century to