Mesenchymal Stem Cells and Craniofacial Regeneration

Mesenchymal Stromal Progenitor/Stem Cells (MSCs) are not a large population of non-hematopoietic stromal cells. This type of cells is usually present in the most connective tissues and bone marrow of the body. They can be isolated from a lot of tissues, such as endometrial polyps, adipose tissue, umbilical cord, menses blood, bone marrow, etc. MSCs have been defined following isolation and culture expansion, by their expression of different molecules including CD90, CD73 and CD105 and the negative markers like CD45, CD34 and CD14. MSCs have the proliferation ability in culture in uncommitted state, while retaining their pluripotency, which makes them attractive effector for biological cell-based tissue repair approaches. MSCs could be differentiated to several cell lineages. Furthermore, the exclusive biological properties of MSCs are mediated by paracrine mechanisms and by intensive immunomodulatory activity. The MSCs use for treatment has been fund and evaluated to be very useful in some pre-clinical animal models and in clinical trials. MSCs and MSC-like cells have low rates of homing to target tissues and organs, limiting therapeutic efficacy. Thus, researches of the homing mechanisms and homing factors of MSCs may lead to the development of therapies with the potential to promote clinical applications of MSCs.

Since three-dimensional printing (3DP) technology was first invented in 1980s, it has been used in a range of fields, including architecture, manufacturing, engineering, education and medicine. In dentistry, 3DP provides a rapid and precise technology that helps diagnosis, treatment planning and treatment of various dental diseases. In craniofacial regeneration, 3DP helps to design and fabricate dental prosthesis and implants, and it also improves craniofacial tissue engineering. Not only scaffolds can be printed by 3DP, stem cells and growth factors can also be controlled and printed by 3DP. 3DP technology has become a major tool in craniofacial regeneration.

Since it was first demonstrated that induced pluripotent stem cells (iPS cells) could be derived from mature cells, significant progress has been made in the field of acquisition, characteristics, identification and application of iPS cells. Until now, diverse means have been proven to generate iPS cells successfully in many biological species and more cell types. Meanwhile, researchers continue to target the efficiency of induction. To identify the characteristics of induced pluripotent stem cells and attest to their pluripotency, one must verify the expression of new derived stem cell genes and proteins, doubling times, methylation patterns, teratoma formation, embryoid body formation, viable chimera formation and capacity to differentiate into all cell types. In other words, induced pluripotent stem cells are theoretically similar, or even same, to natural pluripotent stem cells, for instance embryonic stem (ES) cells. Furthermore, iPS cells have the potential to take the place of ES cells eventually, from which numerous ethical difficulties arise for the treatment of a mass of diseases, for use in therapeutics for drug discovery, disease modeling and regenerative medicine, etc. However, many problems exist as barriers to clinical transformation, including risk for induced oncogenesis and the stability of reprogramming. Here we summarize the current acquaintance of iPS generation and evaluate the advantages and disadvantages of their applications in clinical medicine.

Injuries in the cranial and maxillofacial region are clinically important because this region contains the most exposed parts of the body and is important for expression of social etiquette. Currently, the most common methods used to repair cranial and maxillofacial defects are autologous tissue transplantation and artificial composite material reparation. However, these methods have limitations. In recent years, tissue engineering has been developed as an alternative method of craniofacial reparation and reconstruction. Stem cell therapy is an emerging strategy that may potentially be used for the reconstruction of craniofacial defects.

Transplantation of mesenchymal stem/stromal cells (MSCs) is an emerging treatment for various hard-to-treat diseases. In recent decades, cell sheet technology (CST) has been exploited as a novel promising scaffold-free approach for cell culturing and delivering in tissue regeneration. Results have demonstrated that MSCs facilitate cell viability and function in the CST co-culture system to improve transplantation efficiency. There are extensive interests in developing strategies to enhance the formation of cell sheets with MSC for downstream applications. Novel fabrication techniques have been emerging in recent years, including temperature-responsive system, electroactive responsive system, oxide surface assistant electrochemical system, light responsive system, PH responsive system, magnetite nanoparticles and magnetic force system. This chapter summarizes recent studies in cell sheet engineering and its combination with MSC for tissue regeneration.

In the field of regenerative medicine and tissue engineering, biomaterials are critical for the encouragement and maintenance of biological activities. Scaffolds can be cell-instructive, structural and fabricated from smart materials. Design considerations include the creation of well-defined materials, cell-material interactions, and controlled-release bioactive agents.

A tooth is a compound organ, which is composed of calcified tissues of enamel, dentin and cementum, and a soft connective tissue of dental pulp in which blood vessels and nerves are protected. Periodontal ligaments anchor teeth into the alveolar bone in the jaw to ensure the proper function of teeth. In humans, tooth loss can not only lead to physical and mental suffering, but also affect the aesthetics, which compromise an individual’s quality of life and self-esteem. With the development of tissue engineering, regenerating a whole tooth for clinical tooth replacement is now considered to be an acceptable scientific objective. This subject has a number of challenges for investigators over complicated disciplines including biology, dental medicine and biomaterial science. This chapter will summarize the current knowledge related to tooth regeneration, especially focus on dentin regeneration, periodontal ligament regeneration, and dental pulp regeneration.