Stem Cells

Author: Gianpiero Pescarmona
Date: 21/06/2010

2013-03-31T10:35:54 - Gianpiero Pescarmona

Dental Stem Cells

In recent years, stem cell research has grown exponentially owing to the recognition that stem cell-based therapies have the potential to improve the life of patients with conditions that range from Alzheimer's disease to cardiac ischemia and regenerative medicine, like bone or tooth loss. Based on their ability to rescue and/or repair injured tissue and partially restore organ function, multiple types of stem/progenitor cells have been speculated. Growing evidence demonstrates that stem cells are primarily found in niches and that certain tissues contain more stem cells than others. Among these tissues, the dental tissues are considered a rich source of mesenchymal stem cells that are suitable for tissue engineering applications. It is known that these stem cells have the potential to differentiate into several cell types, including odontoblasts, neural progenitors, osteoblasts, chondrocytes, and adipocytes. In dentistry, stem cell biology and tissue engineering are of great interest since may provide an innovative for generation of clinical material and/or tissue regeneration. Mesenchymal stem cells were demonstrated in dental tissues, including dental pulp, periodontal ligament, dental papilla, and dental follicle. These stem cells can be isolated and grown under defined tissue culture conditions, and are potential cells for use in tissue engineering, including, dental tissue, nerves and bone regeneration. More recently, another source of stem cell has been successfully generated from human somatic cells into a pluripotent stage, the induced pluripotent stem cells (iPS cells), allowing creation of patient- and disease-specific stem cells. Collectively, the multipotency, high proliferation rates, and accessibility make the dental stem cell an attractive source of mesenchymal stem cells for tissue regeneration.

Rimondini L. , Mele S., L’impiego delle cellule staminali in odontoiatria, Minerva Stomatologica 2009 Ottobre
Ulmer FL, Winkel A, Kohorst P, Stiesch M.,Stem cells--prospects in dentistry., 2010

regoulation of differentiation

The essential element for the regulation of expression and differentiation of stem cells are the NOTCH) pathway. The NOTCH signaling pathway is a highly conserved cell signaling system present in most multicellular organisms. NOTCH receptor is composed of a voluminous extracellular portion associated with non-covalent interaction and calcium-dependent to a smaller portion which includes a part extracellular, transmembrane helix and a single-step intracellular part. In the extracellular portion, this protein has several cysteine-rich domains called "EGF-like domains." In such domains, in addition, the receptor is glycosylated presents, in particular with glucose molecules linked fucose and by means of an O-glycosyl bond axis protein. The NOTCH protein spans the cell membrane, with part of it inside and part outside. Ligand proteins binding to the extracellular domain induce proteolytic cleavage and release of the intracellular domain, which enters the cell nucleus to modify gene expression.
Because most ligands are also transmembrane proteins, the receptor is normally triggered only from direct cell-to-cell contact. In this way, groups of cells can organise themselves, such that, if one cell expresses a given trait, this may be switched off in neighbour cells by the intercellular notch signal. In this way, groups of cells influence one another to make large structures. Thus, lateral inhibition mechanisms are key to Notch signaling. The NOTCH cascade consists of notch and notch ligands, as well as intracellular proteins transmitting the notch signal to the cell's nucleus. Although the activation of NOTCH promotes survival of stem cells, their function depends on the type, status, and developmental context of cell.

Cell Cycle. 2012 Jan 15.Fine-tuning of the intracellular canonical Notch signaling pathway.Borggrefe T, Liefke R.

Dental injuries and NOTCH signaling pathway

The mechanisms that contribute to the damage dental include the induction of apoptosis, activation of the immune response and physiological alterations of dental tissues. In many circumstances the formation of apoptotic cells occurs with considerable speed without causing an inflammatory response. Apoptosis is significantly more frequent in the odontoblastic layer that in the rest of the pulp. It 's possible that the elimination of odontoblasts by apoptosis can produce death signals simultaneously leading to the elimination of progenitor cells nearby. The elimination of odontoblasts and progenitors by apoptosis cause the migration of significant numbers of DPSC to the lesion site where they differentiate into odontoblasts thus ensuring the regenerative capacity of the pulp. These cells are activated after injury, proliferate and eventually differentiate into odontoblasts. Numerous significant physiological changes (for example the levels of signaling molecules, the arterial oxygen content) normally accompany regeneration of the dentin and the pulp. Signaling molecules are released from dentin after injury to play a role in the formation of reparative dentin. Given the importance of Notch signaling in the regulation of stem cell behavior and fate of many tissues and organs is hypothesized that this signaling pathway may be important for homeostasis and repair of teeth. In fact, previous studies have shown that the Notch receptors were absent in adult tissue pulp rat, but their expression has been reactivated after injury dental. NOTCH2 was found in the cells of the odontoblastic substrate. NOTCH1 in the cells in the vicinity of the lesion. The lingand Deltalike1 was found in odontoblasts of molars wounded. When Notch is activated by Jagged1 or NICD, inhibits the odontoblastic differentiation without affecting proliferation of cells of the pulp. In contrast studies on human DPSCs have demonstrated that activation by Deltalike1 stimulates both proliferation and differentiation cell. These two results together suggest that the signal Notch can act both in a negative way through activation Jagged1 both in a positive way through Deltalike1 regulating the differentiation.

Mitsiadis TA, Feki A, Papaccio G, Catón J.,Dental pulp stem cells, niches, and notch signaling in tooth injury., 2011 Jul.

Type of dental stem cells

DPSC: Dental pulp stem cells, present in the dental pulp, endowed with remarkable plasticity (can differentiate into adipocytes, chondrocytes, osteoblasts) and high rates of proliferation.
SHED: are obtained from deciduous teeth, have a higher plasticity than DPSC (can differentiate into neural cell, odontogenic cell and adipocytes), have very high rates of proliferation.
PDLSC: derived from the periodontal ligament, recently discovered, are poorly understood even all possible uses, but proved very useful in the regeneration of the periodontal ligament.
SCAP: recently discovered dental papilla at the apex of the root developing (before the eruption), have reduced plasticity, however, have been used in conjunction with PDSC to create a tooth.
DFCS: derived from the dental follicle and can differentiate into cells such as osteoblasts and cementoblasts.

Huang GT, Gronthos S, Shi S., Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine., 2009 Sep.

Dental Pulp Stem Cells (DPSC)

The stem cells of the dental pulp (DPSC) have their origin in the embryonic neural crest and are found in the adult within the area of the dental pulp, rich source of mesenchymal stem cells. These cells are involved in the development of different hard tissues, including crown and root dentin, cement and alveolar bone. Cells are multipotent: this feature facilitates their expansion in vivo and enhances the transforming potential of these cells, these cells can be easily cryopreserved, expressing their regenerative power even years after their extraction from tissues, and their use has great prospects in tissue engineering.

Janebodin K, Horst OV, Ieronimakis N, Balasundaram G, Reesukumal K, Pratumvinit B, Reyes M., Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice., 2011 Nov 8.

DPSC to produce dentine

The dentinal repair postnatal organism occurs through the activity of specialized cells, the odontoblasts, which are believed to be maintained by an as yet undefined precursor population associated with pulp tissue. In two studies conducted by Gronthos was isolated a population of rapidly proliferating cells from pulp tissue of third molars adults. These DPSCs were then compared with the stromal cells of human bone marrow (BMSC), known precursors of osteoblasts. The observation has shown that, although the two populations share a similar immunophenotype in vitro, DPSCs, contrary to BMSC, produced sporadically nodules densely calcified and did not produce adipocytes. When DPSCs were transplanted into immunocompromised mice, they generated a dentin-like structure lined with human odontoblast-like cells that surrounded a pulp-like interstitial tissue. In contrast, BMSCs formed lamellar bone containing osteocytes and surface-lining osteoblasts, surrounding a fibrous vascular tissue with active hematopoiesis and adipocytes.

Gronthos S, Mankani M, Brahim J, Robey PG, Shi S., Postnatal human dental pulp stem cells in vitro and in vivo.,2000 Dec 5."

DPSC to produce bone

To prove this theory research group at the University of Naples has used a biocomplex built by stem cells from pulp tissue (DPSC) and a collagen sponge scaffold for oro-maxillofacial (OMF), using it for tissue repair mandibular bone in patients requiring extraction of third molars. The patients had bilateral resorption of the alveolar ridge distal to the second molar secondary to constipation of the third molar the alveolar cortical plate, producing a defect without walls, at least 1.5 cm in height. This clinical condition does not allow spontaneous repair bone after extraction of the third molar, and eventually leads to the loss also adjacent the second molar. Third upper molars were extracted before the DPC for the isolation and expansion. The cells were then seeded on a collagen sponge and the scaffold biocomplex obtained was used to fill the lesion site left by extraction of the third lower molars. Three months after autologous DPC, alveolar bone of patients had complete repair and restoration of optimal vertical periodontal tissue behind the second molars, as assessed by clinical probing and X-rays. Histological observations clearly demonstrated the complete bone regeneration at the injury site. Optimal bone regeneration was evident one year after grafting. This clinical study demonstrates that a DPC / collagen sponge biocomplex can fully restore human jaw bone defects and indicates that this cell population could be used for the repair and / or regeneration of tissues and organs.

D'Aquino R, De Rosa A, Lanza V, Tirino V, Laino L, Graziano A, Desiderio V, Laino G, Papaccio G., Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes., 2009 Nov 12."


The DPSCs are multipotent stem cells present in abundance in the dental pulp, collecting them is a non-invasive practice that can be performed during the juvenile and adult life after the common practice surgical extraction of wisdom teeth and sacrifices to the very limited tissue . Due to their multipotency by DPSCs is possible to obtain a wide range of cellular variants that, once transplanted, lead to the formation of vascularized tissues perfectly integrated with the surrounding environment. These features suggest a further use of the DSCP in tissue engineering and for clinical use in several diseases that require bone growth and tissue repair.

by Federico Amoroso

2013-03-31T10:33:48 - Gianpiero Pescarmona

Stem Cells

Definition: Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

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  • National Institute of health, Stem Cells Information, Stem Cells Basics, chapter 1 Introduction
  • National Institute of health, Stem Cells: Scientific Progress and Future Research Direction, the stem cell, chapter 1, June 17, 2001

Proprieties: Stem cells differ from other types of cells in the body. All stem cells—regardless of their source—have three general properties:

  • They are capable of dividing and renewing themselves for long periods
  • They are unspecialized
  • They can give rise to specialized cell types

- National Institute of health, Stem Cells Information, Stem Cells Basics, chapter 2 Proprieties

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Potency specifies the differentiation potential of the stem cell:
Totipotent: stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism. These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.
Pluripotent: stem cells are the descendants of totipotent cells and can differentiate into nearly all cells, i.e. cells derived from any of the three geerm layers.
Multipotent: stem cells can differentiate into a number of cells, but only those of a closely related family of cells.
Oligopotent: stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells.
Unipotent: cells can produce only one cell type, their own, but have the property of self-renewal, which distinguishes them from non-stem cells (e.g., muscle stem cells)

National Institute of health, Stem Cells Information, Stem Cells Basics

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Classification according to the source of lead:

National Institute of health, Stem Cells Information, Stem Cells Basics, chapters 3-4

National Institute of health, Stem Cells: Scientific Progress and Future Research Direction, the stem cell, Human Embryonic,June 17, 2001

National Institute of health, Stem Cells: Scientific Progress and Future Research Direction, Stem Cells and Embryonic Germ Cells, Appendix C,June 17, 2001

Henry E. Young, Asa C. Black Jr., Adult stem cells, 23 DEC 2003

ASC/ESC similaritis and differences:

Human embryonic and adult stem cells each have advantages and disadvantages regarding potential use for cell-based regenerative therapies. One major difference between adult and embryonic stem cells is their different abilities in the number and type of differentiated cell types they can become. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are thought to be limited to differentiating into different cell types of their tissue of origin.
National Institute of health, Stem Cells Information, Stem Cells Basics, chapter 5

Metods of use:

The induced pluripotent stem cells( Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors, Cell, Volume 131, Issue 5, 30 November 2007), commonly abbreviated iPSCs or iPS (Induced pluripotent Stem Cells) are a type of pluripotent stem cells, artificially derived from a non-pluripotent cell, typically an adult somatic cell.
It is thought that the induced pluripotent stem cells are identical to their natural counterparts, such as embryonic stem cells in many respects, as the expression of certain genes and proteins, chromatin methylation patterns, times of division, formation of the embryonic nucleus , formation of teratomas, power and distinctness.

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IPS cells are typically derived by transfection of particular genes associated with stem cells, pluripotent cells within. For transfection refers to the process of introduction of exogenous biological material in eukaryotic cells and in most cases of mammal. It is more frequent the insertion of genetic material, usually including DNA and siRNA, but, in general, may also be transfected proteins (such as antibodies). The process of transfection can be done:
in vitro - on target cells in cell culture in the long term;
Ex vivo - cells isolated from an organism and transferred to culture medium;
in vivo - directly on cells of an organism

Transfection methods:
Chemical methods (calcium phosphate, liposomes, dendrimers)
Physical methods (electroporation, microinjection, gene gun method)
Methods through viruses (adenovirus, retrovirus and lentivirus)

Clinical Use:

  • Reproductive cloning (not ethically permissible)
  • Cloning to produce reserve cells for tissue regeneration
  • Creation of histo-compatible cell banks
  • solation and propagation of cells for transplantation (regenerative purposes)
  • solation and propagation of cells to form artificial organs

by Federico Amoroso

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