Stem cells: A potential regenerative future in dentistry

In the face of extraordinary advances in the prevention, diagnosis, and treatment of human diseases, devastating illnesses such as heart disease, diabetes, cancer, and diseases of the nervous system, such as Parkinson’s disease and Alzheimer’s disease, continues to deprive people of health, independence, and well-being. Research in human developmental biology has led to the discovery of human stem cells. Stem cells are primitive cells found in all multi-cellular organisms that are characterized by self-renewal and the capacity to differentiate into any mature cell type. These stem cells have the awesome potential for regeneration and may be used to replace or repair damaged cells, and have the potential to drastically change the treatment of conditions like cancer, Alzheimer’s and Parkinson’s disease and even paralysis. There are 2 main types of stem cells – embryonic stem cells and adult stem cells – which are classifi ed according to their origin and differentiation potential.[2] Mesenchymal stem cells (MSCs), a type of the adult stem cells that can be harvested from bone marrow and other sources such as liver, umbilical cord, placenta, adipose tissue, synovial membrane, amniotic fl uid and even teeth,[3] have increasingly played a central role in regenerative medicine. Their attractiveness is found in their multipotency to differentiate and develop into various types of tissues such as adipose, cartilage, and bone,[4] as well as their promising use in patient-specifi c gene therapy.[3] Stem cells are defi ned as having the capacity for extensive self-renewal and for originating at least one type of highly differentiated descendant.[5] Research in the stem cell fi eld grew out of fi ndings by Canadian scientists Ernest A. McCulloch and James E. Till in the 1960.[6,7] Stem cells are cells that have the following capabilities: First, they are able to continuously produce daughter cells having the same characteristics as themselves (self-renewal); secondly, they can generate daughter cells that have different, more restricted properties, and finally, they can re-populate a host in vivo (differentiation).[8] Access this article online Quick Response Code: Website: www.ijhg.com


Introduction
Judging from the explosion of articles not only in scientifi c journals, but also in the mass media and on the internet, one could say the term "stem cells" has become linked to the word "cure." [1] In the face of extraordinary advances in the prevention, diagnosis, and treatment of human diseases, devastating illnesses such as heart disease, diabetes, cancer, and diseases of the nervous system, such as Parkinson's disease and Alzheimer's disease, continues to deprive people of health, independence, and well-being.
Research in human developmental biology has led to the discovery of human stem cells.
Stem cells are primitive cells found in all multi-cellular organisms that are characterized by self-renewal and the capacity to differentiate into any mature cell type. These stem cells have the awesome potential for regeneration and may be used to replace or repair damaged cells, and have the potential to drastically change the treatment of conditions like cancer, Alzheimer's and Parkinson's disease and even paralysis.
There are 2 main types of stem cells -embryonic stem cells and adult stem cells -which are classifi ed according to their origin and differentiation potential. [2] Mesenchymal stem cells (MSCs), a type of the adult stem cells that can be harvested from bone marrow and other sources such as liver, umbilical cord, placenta, adipose tissue, synovial membrane, amniotic fl uid and even teeth, [3] have increasingly played a central role in regenerative medicine. Their attractiveness is found in their multipotency to differentiate and develop into various types of tissues such as adipose, cartilage, and bone, [4] as well as their promising use in patient-specifi c gene therapy. [3] Stem cells are defi ned as having the capacity for extensive self-renewal and for originating at least one type of highly differentiated descendant. [5] Research in the stem cell fi eld grew out of fi ndings by Canadian scientists Ernest A. McCulloch and James E.
Till in the 1960. [6,7] Stem cells are cells that have the following capabilities: First, they are able to continuously produce daughter cells having the same characteristics as themselves (self-renewal); secondly, they can generate daughter cells that have different, more restricted properties, and finally, they can re-populate a host in vivo (differentiation). [8]  In recent years, the fi eld of dentistry has embossed its presence by taking major leaps in research and further bringing it into practice. The most valuable ongoing research in regenerative dentistry is the study on stem cells. It was instituted that stem cells grow rapidly and have the potential to form specialized dentin, bone, and neuronal cells. These neuronal cells can be used for dental therapies and can provide better treatment options for patients. The stem cells based therapies could help in new advances in treating damaged teeth, inducing bone regeneration and treating neural injury as well.

Sources of Stem Cells
There are many potential sources for stem cells. 3. Adult stem cells that are de rived from mature tissues and are found in adult tissues. They act as a repair system for the body, replenishing specialized cells, but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. [9] The development of mouse ES cells in 1981 provided the paradigm and much of the technology, for the development of human ES cells, but the concept of a pluripotent embryonic cell is far older than that. [ [10] Thus far, only mouse EG or ES cells meet these generic criteria. Primate ES cells meet the fi rst 3 criteria's, but not the last.

Growth of Stem Cells in the Laboratory
Growing cells in the laboratory is known as cell culture. Human embryonic stem cells are isolated by transferring the inner cell mass into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. The cells divide and spread over the surface of the dish and form clonogenic adherent cell clusters with a fi broblastic morphology (colony-forming units-fi broblast [CFU-F]) in vitro. The inner surface of the culture dish is typically coated with mouse embryonic skin cells (feeder layer). The reason for having the mouse cells in the bottom of the culture dish is to give the inner cell mass cells a sticky surface to which they can attach. Also, the feeder cells release nutrients into the culture medium. [8] Recently; scientists have begun to devise ways of growing embryonic stem cells without the mouse feeder cells because of the risk that viruses or other macromolecules in the mouse cells may be transmitted to the human cells by adding a single cytokine, leukemia inhibitory factor (LIF) into the culture medium could sustain mouse ES cell self-renewal in the absence of feeders. [11,12] Periodontal ligament stem cells (PDLSCs) were identifi ed as a specifi c MSC population derived from periodontal ligament with expression of array of osteogenic markers like alkaline phosphatase (ALP), matrix extracellular phosphoglycoprotein (MEPE), bone sialoprotein (BSP), and osteocalcin; mesenchymal stem cell marker STRO-1; and tendon marker scleraxis. Also, human ES cells can be maintained on stromal cells in the presence of basic fi broblast growth factor (b-FGF).

Characteristics of Mesenchymal Stem Cells
MSCs are described as multipotent because of their ability, even as clonally isolated cells, to exhibit the potential for differentiation into a variety of different cells/ tissue lineages. MSCs have the ability to differentiate along specifi c mesenchymal lineages and when induced to do so, to remain in a quiescent undifferentiated state until provided the signal to divide asymmetrically, and fi nally, to undergo many more replicative cycles than normal, fully-differentiated cells. [13]

Properties of Stem Cells
All primate pluripotent stem cells grow in more rounded clumps with indistinct cell borders express alkaline phosphatase activity. In humans, there are 4 different isozymes of alkaline phosphatase. EC cells express the tissue non-specifi c form and a form of the enzyme that can be detected by antibodies that react with the germ cell or placental form. [8] The pluripotent cells require a mouse embryonic fi broblast feeder-cell layer for support.

In the case of mouse ES and EG cells, this requirement can be replaced by LIF or by related members of this cytokine family, but pluripotent human EC cells, rhesus monkey ES cells, and human ES cells will not respond
to LIF in such a fashion. [10]

Periodontal Ligament Stem Cells
The concept that stem cells may reside in the periodontal tissues was first proposed almost 20 years ago by Melcher. Since periodontal regeneration is essentially a re-enhancement of the development process including morphogenesis, cytodiferentiation, extracellular matrix production and mineralization, such processes support the concept that some mesenchymal stem cells remain within the periodontal ligament and are responsible for tissue homeostasis. These mesenchymal stem cells serve as a source of renewable progenitor cells generating cementoblasts, osteoblasts, and fi broblasts throughout adult life. The periodontal ligament stem cell cultures exhibit approximately 30% higher rates of proliferation compared to the growth of cultured bone marrow stromal stem cells. It appears that these cells maintain this capacity of higher growth potential beyond 100 population doublings before in vitro senescence is noted. [14] The putative stem cell marker, STRO-1, used to isolate and purify bone marrow stromal stem cells, is also expressed by human periodontal ligament stem cells and dental pulp stem cells. [14] Clinical  [15] Several craniofacial structures-such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue-have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches.
Adult mesenchymal stem cells have advantages over embryonic stem cells for tissue engineering of the mandibular condyle, because adult mesenchymal stem cells (MSCs) can be obtained from the same individual and readily induced to differentiate into both chondrogenic and osteogenic cells. [16,17] Biomimetic scaffolds are frequently needed to enable cell growth and differentiation to occur in an environment that has been previously unfamiliar to either biologists or engineers.
MSCs have the potential for the regeneration of mammalian dental tissues. Bio-engineered teeth can be derived from cultured tooth bud cells. Deciduous teeth contain a population of more immature multipotent stem cells, which are capable of forming dentin-like structures but not a complete dentin-pulp complex. The developed bio-engineered tooth had a well-defi ned pulp chambers, odontoblasts, pre-dentin, and dentin. It also contained a morphologically correct enamel organ consisting of stellate reticulum, stratum intermedium, ameloblasts, and dental enamel. In addition, putative Hertwig's root sheath epithelia were also present. [14,18,19] Dental pulp stem cells were capable of generating a reparative dentin-like structure directly on the surface of human dentin. [20] It has been demonstrated that human PDL contains that are involved in the initial formation of both dental and periodontal attachment tissues. In short, this approach is intended to mimic the normal biological process that occurs as these tissues are formed early in development. [21,22]  The proliferative potential of MSC decreases faster after 120 days of in vitro expansion. [23] Challenges Vast unequal resources, differential standards of public health, and uneven opportunities for health care within and between countries comprises a major hurdle in achieving substantial success in the fi eld of genetics.

Aging of Mesenchymal Stem Cell
The World Health Organization has reminded member states that "justice demands equitable access to genetic services" and has also stated that "Genetic services for the prevention, diagnosis, and treatment of disease should be available to all, regardless of the cost factor, and should be provided fi rst to those whose needs are the greatest." Along with these, funding for the purpose of research should be taken into account. The federal government is the only realistic source for such an infusion of funds.
Without the stimulus of public funding, new treatments could be substantially delayed. [9] Conclusion Electron microscope radio-autography was used in an attempt to identify any relationship between the location and degree of differentiation of progenitor cells