StemCell Therapy

Abstract

Stem cells are primitive cells that can differentiate and regenerate organs in different parts of the body such as heart, bones, muscles and nervous system. This has been a field of great clinical interest with immense possibilities of using the stem cells in regeneration of human organ those are damaged due to disease, developmental defects and accident. The knowledge of stem cell technology is increasing quickly in all medical specialties and in dental field too. Stem cells of dental origin appears to hold the key to various cell-based therapies in regenerative medicine, but most avenues are in experimental stages and many procedures are undergoing standardization and validation. Long-term preservation of SHED cells or DPSC is becoming a popular consideration, similar to the banking of umbilical cord blood. Dental pulp stem cells (DPSCs) are the adult multipotent cells that reside in the cell rich zone of the dental pulp. The multipotent nature of these DPSCs may be utilized in both dental and medical applications. A systematic review of the literature was performed using various internet based search engines (PubMed, Medline Plus, Cochrane, Medknow, Ebsco, Science Direct, Hinari, WebMD, IndMed, Embase) using keywords like dental pulp stem cells, regeneration, medical applications, tissue engineering. DPSCs appears to be a promising innovation for the re-growth of tissues however, long term clinical studies need to be carried out that could establish some authentic guidelines in this perspective.

KEYWORDS: Dental pulp stem cells, myocardial infarction, regenerative therapy, tissue engineering

The term stem cell was proposed for scientific use by Russian histologist Alexander Maksimov in 1909. He was the first to suggest the existence of hematopoietic stem cells (HSC) with the morphological appearance of a lymphocyte, capable of migrating throughout the blood to micro ecological niches that would allow them to proliferate and differentiate.[1] Tissue engineering as a scientific discipline has shown promising results in the field of dentistry also. Tissue engineering approaches can aid in either the replacement of damaged tooth structures and/or in the repair/regeneration of pulp-dentin complex (regenerative endodontics).

The science of tissue engineering and regenerative medicine has seen tremendous development, especially in the field of stem cell research. Tissue engineering approach requires the three main key elements (triad): Stem cells, scaffold (or matrix) and growth factors (morphogens).[2] These key elements can be used in three principal therapeutic strategies to obtain the desired result. Today stem cell biology is one of the most fascinating areas of science which brings in the hope for improved outcomes by replacing damaged or absent tissues with healthy regenerated tissue.[3] Dental pulp stem cells (DPSCs) can be found within the cell rich zone of dental pulp. Their embryonic origin, from neural crests, explains their multipotency.[4] The term stem cell was projected by Alexander Maksimov a Russian histologist, during 1908 in congress of hematologic society at Berlin.[5] Stem cells have the potential to renew themselves for long periods through cell division and under certain physiologic or experimental conditions, they can be induced to become cells with special functions.[6] Several studies have been carried out to verify whether stem cells could become a source of stable differentiated cells. These studies have confirmed their capacity to induce tissue formation during the embryonic development and proliferation along with differentiation to generate all other tissues.[7,8,9,10]

By definition the pluripotency of biological compounds describes the ability of certain substances to produce several distinct biological responses whereas multipotency means the ability to differentiate to a limited number of cell fates or into closely related family of cells. Recent advances in the tissue engineering have drawn scientists to test the possibility of tooth engineering and regeneration. However, these biotechnologies are in its initial phase, it is expected to be used to restore missing teeth and replace artificial dental implants.

Researchers have observed that these stem cells act differently than other adult stem cells. These dentally-derived mesenchymal stem cells are capable of extensive proliferation and differentiation, which makes them an important resource of stem cells for regeneration and repair of a multitude of diseased and injured organs and tissues.[10,11] Because of their ability to produce and secrete neurotrophic factors, these stem cells may also be beneficial for the treatment of neurodegenerative diseases and the repair of motoneurons following the injury. Research works on dental mesenchymal stem cells is expanding at an unprecedented rate. More than 1,000 research studies from institutions around the world have been published since the year 2000 that make reference to the dental stem cells. In the year 2007 alone, over 1,000 research articles were published on Dental Stem Cells.[12] Additionally, over 60 clinical investigations with animals and human volunteers have been published seeking to identify the potential new medical treatments from adult stem cells.[10] Stem cell-based therapies are being investigated for the treatment of many conditions including: Neurodegenerative conditions, liver disease, diabetes, cardiovascular disease, autoimmune diseases, musculoskeletal disorders, and for nerve regeneration following the brain or spinal cord injury.

Riccardo and co workers postulated two school of thoughts; one argues that these cells produce a dentin-like tissue,[7] whereas the other research group[11] has demonstrated that these cells are capable of producing bone, both in vitro and in vivo. Beyond natural capacity of response to the injury, dental pulp stem cells are attractive for their potential to differentiate, in vitro, into several cell types including odontoblasts, neural progenitors, chondrocytes, endotheliocytes, adipocytes, smooth muscle cells and osteoblasts.[12,13] The potential application of dental pulp stem cells and tissue engineering in medicine and dentistry in particularly are discussed in the present review.

At present, the mesenchymal stem cell populations having the high proliferative capacity and multi-lineage differentiation have been isolated from the dental tissues.[14,15] These are dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs), and stem cells from apical papilla (SCAPs). DPSCs and SHEDs originate from the cranial neural crest and express early markers for both mesenchymal and neuroectodermal stem cells.[16,17,18] This explains their multipotency and pluripotency. Sharpe and Young were pioneered the use of stem cells in the dental tissue engineering.[19,20] Various studies have shown that these cells have unique features of stem/progenitor cells having the capacity to differentiate into dentin forming odontoblasts.[21,22] The roots of the third molar are often incomplete at the age of eighteen, therefore these teeth contains a conspicuous pool of undifferentiated cells, resident within the cell rich zone of the dental germ pulp.[23,24] In an in vitro model, Hwang et al. derived DPSCs from supernumerary mesiodens, and it has been seen that DPSCs derived at the stage of crown development are more proliferative than at later stages.[25] Apart from these, the cells obtained from loosely attached tissue at the root apex (SCAP) and periodontal ligament (PDLSC) have been used for bio-root engineering.[26,27,28] More recently, stem cells obtained from the dental tissues have been shown to develop into fat, bone cartilage and neural cells.[29,30]

In addition to their therapeutic use in dentin regeneration, regeneration of periodontal tissues and skeletal articular tissues of craniofacial region, DPSCs were also reported to be used in the treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.[31] This review article is an attempt to highlight main strategies as related to the use of dental pulp stem cells, their characterization, storage, tissue engineering strategies and useful clinical applications in the field of modern dentistry.

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Imperative Role of Dental Pulp Stem Cells in Regenerative ...

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