The cell being the basic unit of all living organisms is the prime determinant factor for the success of tissue engineering. Living cells can be used to restore, maintain, or enhance the function of tissue and organs and can therefore be a significant approach in healthcare therapeutics.
Classification of Stem Cells
Cells that could be used for tissue engineering in a living system can be commonly categorized as stem (unspecialized) and non-stem (specialized).
Stem cells are defined as undifferentiated or immature cells that are able to renew by themselves and differentiate into tissue-organ-specific cells. They are generally classified into three types and are used for site-specific applications, according to their potency:
- Totipotent stem cells: generate all types of cells including embryonic stem cells.
- Pluripotent stem cells: generate all types of cells except embryonic stem cells.
- Multipotent stem cells: produce a limited number of cells/tissues with specific functions.
Stem cells can also be classified as embryonic or adult cells based on their source of origin.
- Embryonic Stem Cells
Embryonic stem cells (ESCs) are a similar group of homogenous cells obtained from the embryo and cultivated in vitro. They can differentiate into all cells of the adult body, and can propagate indefinitely.
- Adult Stem Cells
Adult stem cells are undifferentiated cells that exist among differentiated cells in a tissue or organ. They can replicate themselves and are limited to differentiating into distinct cell types of their tissue of origin, therefore being multipotent or unipotent stem cells. The chief roles of adult stem cells are to repair and maintain the tissue in which they exist in.
Applications of Adult Stem Cells
Embryonic stem cell research has a greater potential than that of adult stem cell, but several ethical and legal controversies still exist regarding their use in humans. Whereas adult stem cells have considerable organic and therapeutic interests.
The potential advantage of using adult stem cells is that the patient’s own cells can be easily isolated, cultured and then transplanted wherever regeneration is required. Thus, there is minimal to none coincidental immune rejection, and helps to avoid numerous ethical and legal issues. The disadvantage of adult stem cells is that they are rare in mature tissues, so isolation and expansion in cell culture is challenging.
Adult stem cells are usually collected from bone marrow of flat bones and is mainly made of two distinct stem cell lines:
- Hematopoietic stem cells (HSCs), forming new blood cells
- Mesenchymal stem cells (MSCs), which differentiate into bone cells, neural cells, cartilage, skin cells, muscle cells and corneal cells.
Certain adult stem cell types are pluripotent in nature; they can differentiate into cells originating from any of the three germ layers (ectoderm, mesoderm, and endoderm). This ability to differentiate into multiple cell types is called trans-differentiation or plasticity.
Cells are also categorized by the source of their origin. Autologous cells are obtained from the same patient in whom they will be utilised. These cells are the patient’s own cells and are immune acceptable. The other source is another donor of the same species and are referred to as allogenic cells. From a scientific point of view, the best source of allogenic stem cells are embryos. However, the use of Embryonic Stem Cells for such therapeutic use is contentious from an ethical point of view and is forbidden in many countries.
Dental Stem Cells and Their Sources
A tooth develops as a result of judiciously arranged relations between the oral epithelial ectodermal cells that form the enamel organ and cranial neural crest–derived mesenchymal stem cells (MSCs) that form the dental papilla and dental follicle. Other components of the tooth like dentin, pulp, cementum, and periodontal ligament originate from these MSCs.
While the outer rigid structure of teeth provides hardness and durability, it is susceptible to damage caused by mechanical trauma, chemicals, congenital defects, and bacterial infections. Other mineralized tissues such as bone, have the ability to modify and undergo repair following trauma throughout postnatal life, but enamel is unique due to the apoptosis (programmed cell death) of ameloblasts (cells that form enamel) following tooth formation. In contrast, dentin acts as a protective barrier to the dental pulp, indicating some limited restoration process in the form of reparative dentin.
Dental pulp, a soft connective tissue within the dental crown, is an interesting source of dental stem cells capable of regenerating organized tooth structures damaged due to trauma, caries, and periodontal disease. Since 2000, scientists have isolated and characterized several human dental stem/progenitor cells such as:
- DSCs Dental Stem Cells
- DFPCs Dental Follicle (a loose connective tissue sac surrounding the developing tooth germ before eruption) Precursor Cells
- DPPSCs Dental Pulp Pluripotent-like Stem Cells
- DPSCs Dental Pulp Stem Cells
- PDLSCs PerioDontal Ligament (fibres that attach the tooth to the bone) Stem Cells
- PDLPs PerioDontal Ligament Progenitor cells
- SCAP cells Stem Cells from Apical Papilla
- SHED cells Stem Cells from Human Exfoliated Deciduous teeth
Most of these cells are found and isolated from human permanent and primary teeth, human wisdom teeth, human exfoliated deciduous teeth, apical papilla (tooth root apex), and supernumerary teeth, which are commonly discarded. Since exfoliation of deciduous teeth is a physiological phenomenon and every child has 20 deciduous teeth, gathering them for isolation of adult stem cells is an easy, non-invasive, and ethically accepted method. On the other hand, dental pulp of permanent teeth from elderly patient has certain limitations for stem cell isolation, since the occurrence of stem cells may be greatly restricted in aged pulp cells.
These cells have been characterized as clonogenic (ability to form a large colony or a clone) and highly proliferative. They can also induce dentin and bone formation. They have the ability to differentiate into adipocytes (fat cells), nerve cells, osteoblasts (bone forming cells) and odontoblasts (cells that produce dentine). That means they are multipotent and also show self-renewal abilities. In fact, their multipotency has been linked to those of bone marrow stem cells (BMSCs).
They also play a significant role in balancing inflammation and repair of deep carious lesions or pulp exposures. Tissue engineering studies propose that these cells may be an excellent resource for stem cell therapies, including autologous stem cell transplantation.
Induced Pluripotent Stem Cells [IPSCs]
In 2006, Takahashi and Yamanaka discovered induced pluripotent stem cells (IPSCs) which was a big breakthrough in regenerative science. These cells promise to have all the potential of embryonic stem cells but without constraints such as the ethical issues, availability, and rejection problems as they are autogenic (self-generated).
These cells are reprogrammed somatic cells and by inserting 4 genes (OCT3/4, SOX2, KLF4, and MYC) they return to an embryo-like state. The resultant IPSCs have embryonic stem cell characteristics: they are capable of generating cells from each of the 3 embryonic germ layers (endoderm, mesoderm, and ectoderm) and can propagate in culture indefinitely.
Although IPSCs cells are not truly equal to embryonic stem cells and may even have a memory of the somatic tissue from which they were derived, they have generated great interest for their many potential personalized regenerative therapeutic applications.
The easy availability of Dental Stem Cells (DSCs) makes them a viable source of adult Mesenchymal Stem Cells (MSCs) for regenerative medicine applications. Although much work is essential for translating data from in vitro and animal studies to feasible clinical applications, there are thrilling possibilities for the use of DSCs in tissue engineering and regenerative medicine applications within the root canal, the oral cavity, and in other parts of the body. The relative ease with which these cells can be harvested, coupled with interest in stem cell banking, will likely drive the research that further clarifies their characteristics and potential applications.
Dr. Jasmine Rayapudi is an academician, endodontist and a restorative dentist with a keen interest in research activities including teaching and delivering excellent dental care and restoring confident smiles. She also loves to bake and drive and go on long road trips with her family.