Stem Cell Therapy in Dentistry

[aravind krishnan]

STEM CELLS

TERMINOLOGIES

Tissue Stem cells :

• Potten and Loeffler, 1990 definition
• Stem cells of a particular tissue are undifferentiated cells (relative to a functional tissue) capable of

 1.proliferation;

2. production of a large number of differentiated functional progeny;

3.self-maintenance of their population;

4. regeneration of the tissue after injury;

5.flexibility in the use of these options

• Amended Definition of Tissue Stem Cells

Stem cells of a particular tissue are:

1. a potentially heterogeneous population of functionally undifferentiated cells, capable of:

2. homing to an appropriate growth environment;

3.proliferation;

4. production of a large number of differentiated progeny;

5.self-renewing or self-maintaining their population;

6.regenerating the functional tissue after injury with

7. flexibility and reversibility in the use of these options

• Potency -differentiation potential (the potential to differentiate into different cell types) of the stem cell.

1.Totipotent /omnipotent stem cells –

• differentiate into embryonic and extraembryonic cell types. –
• a complete, viable organism.
• produced from the fusion of an egg and sperm cell.
•  Cells produced by the first few divisions of the fertilized egg are also totipotent.

2.Pluripotent stem cells –

• descendants of totipotent cells
• can differentiate into nearly all cells,  i.e. cells derived from any of the three germ layers.

3. Multipotent stem cells

•  -can differentiate into a number of cells,
• - but only those of a closely related family of cells.

4.Oligopotent stem cells

• can differentiate into only a few cells, such as lymphoid or myeloid stem cells.

5.Unipotent cells

• can produce only one cell type, their own,but have the property of self-renewal,
• - distinguishes them from non-stem cells (e.g., muscle stem cells)

Introduction

• Russian histologist Alexander Maksimov in 1908
• Stem cells grew out of findings by Canadian scientists in the 1960s
• Dental exfoliation-genetically regulated event
• Lost- donot regenerate
• Stem cells-divide to produce one stem cell and one cell capable of differentation .
• Stem Cells in Dentistry
• 2000- Discovery of adult Stem-cells in dental pulp cells, the living tissue at the centre of tooth.
• 2003- Stem-cells found in baby teeth.
• 2004- Stem-cells found in periodontal ligament, which holds the teeth in place in gums.
• 2007- Researchers learn how to reprogram some adult cells from mice to assume a State like Embryonic Stem-cells called induced pluripotent Stem-cells.
• 2008- Cells in dental pulp identified as adult Stemcells.
• 2003 Dr. Songtao Shi - baby tooth Stem-cells by using the deciduous teeth of his six year old daughter-  isolate, grow and preserve these Stem cells with regenerative ability, and he named them as SHED (Stemcells from Human ExfoliateD Deciduous teeth)
• CLASSIFICATION
• two broad types of Stem-cells
• Embryonic stem- cells
•  Adult Stem-cells.
• Embryonic Stem cells
• Pluripotent-differentiate into all types of somatic cells and theoretically divide an unlimited number of times
• Embryoblast cells –part of blastocyst –interest for stem cell research
• Ability to self regenerate
• Adult-Stem cells
• cells are also called as somatic Stem-cells because they refer to body cells
• can only proliferate a limited number of times.
• Distinguished according to their developmental potential. There are uni- and bipotent progenitor cells-only be differentiated into mature cells of their parent tissue
• Multipotent adult stem cells-are not identical to the parent tissue
• Sources Of Stem-Cells
• Bone marrow -from the long bones. The best sources are pelvic bones, femur and sheen bone.
•  Umbilical cord blood -collected just after the birth of the baby.
•  Embryonic cells -from the blastocyst phase of the embryo.
• Placental Stem-cells
•  Menstrual Stem-cells -extra-ordinary improvement over the umbilical cord blood cells-  have a rapid growth rate.
•  Dental Stem-cells -from the pulp of deciduous or wisdom teeth. - has been found to produce bones, cartilage, and muscle cells if cultured.
•  Present in natal teeth, mesiodense or supernumerary teeth.
• Applications- Parkinson’s diseases,paraplegia, leukemia, and brain tumors
• therapeutic use in dentistry - to regenerate individual tissue types- such as bone,periodontal tissue
• Someday even entire teeth
• 2 means of regenerating teeth
• 1.conventional tissue engineering-the application of cells in a carrier material in vitro under the influence of a stimulus leads to tissue regeneration.
• 2. using dental epithelium and mesenchymal cells in vivo after direct implantation
• - Based on knowledge of general embryogenesis and physiological tooth development during childhood
• CLINICAL APPLICATIONS
• Craniofacial applications.
•  Dental pulp applications.
• Creation of artificial embryonic teeth primordia fromcultured cells.
• Cementoblast like cells applications.
• Periodontal regeneration.
• Over 200 regulatory genes-odontogenesis
• Growth factors from four families
• 1. fibroblast growth factor (FGF),
• 2.Hedgehog,
• 3.wingless (WNT)
• 4. transforming growth factor- (TGF-), to which the bone
• morphogenic proteins (BMPs) belong
• The basis for the regeneration of teeth or individual dental tissues –
• is the acquisition of suitable stem cells and
•  a suitable environment in which these cells can
•  differentiate into the target tissues
• Carrier materials
• collagen sponges
• HA/TCP (hydroxyapatite tricalcium phosphate
• calcium phosphate
• fibrin polymer ceramic
• alginate
• or polymers
•  PCL gelatin scaffolds
• the use of growth factors such as fibroblast growth factors
• and some of the transforming growth factor  family, e. g. bone morphogenic proteins

Dental epithelial stem cells

• The embryonic oral epithelium induces odontogenesis
• Ameloblasts- arise from epithelial stem cells
• the only cells of ectodermal origin which play a role in odontogenesis.
• Lost after tooth eruption- leaving no adult human ectodermal stem cells available for cell therapy.
• Dental epithelial stem cells –obtained from third molars of newborn or juvenile, still developing animals
• A source of epithelial stem cells,
• -the apical bud cells (ABCs), in the apical epithelium is responsible for continuous enamel production
• Dental mesenchymal stem cells
• With the exception of ameloblast progenitor cells,all stem cells involved in odontogenesis originate in mesenchyme
• Mesenchymal stem cells - differentiate into nerve, muscle, vascular, fat, cartilage or bone cells

STEM CELLS	Target  Tissue /tissue  cells
DPSCs	Odontoblasts, dentin and pulp tisue,osteoblast Chondrocytes Adipocytes Endotheliocytes,neurons,Musculature
SHEDs	Odontoblsts ,Osteoblasts,neurons,Adipocytes,endotheliocytes
PDLSCs	Odontoblasts,Periodontal  tissue ,Osteoblasts,Cementoblasts, Chondrocytes,adipocytes
DFSCs	PDL progenitor cells Osteoblast Cementoblasts Neuroblasts
SCAPs	Odontoblasts,osteoblast

• Dental pulp stem cells
• isolated from the dental pulp
• Depending on specific signals from their environment, DPSCs can either regenerate new stem cells or undergo  a differentiation process.
• Dental pulp acquired from third molars or pulpectomized teeth left in situ.
• Even after temporary storage in liquid nitrogen- the DPSCs do not lose their multipotent ability to differentiate
• In vitro, DPSCs - differentiate to odontoblasts, osteoblasts, endothelocytes, smooth muscle cells, adipocytes, chondrocytes, and neurons.
• DPSCs differentiate in vitro to osteoblast progenitor cells and mature into osteoblasts which produce LAB (living autologous fibrous bone tissue
• DPSCs in vivo can form calcified bone tissue with Haversian canals and osteocytes and dentin/pulp-like tissue complexes
• odontogenic, myogenic, adipogenic, and osteogenic differentiation.
•  DPSCs influence angiogenesis
• Regeneration potential of adult stem cells in human dental pulp - tertiary dentin
• therapeutically employed for direct and indirect pulp capping after caries excavation near the pulp
• Stem cells from human exfoliated deciduous teeth (SHEDs
• relatively easily accessible source of adult stem cells
• coronal pulp of exfoliated deciduous teeth
• Role
• in the eruption of permanent teeth
• influence the osteogenesis
• In vitro-odontogenically, osteogenically, adipogenically, chondrogenically, or neurally
• In vivo- neurons, adipocytes, odontoblasts, and osteoinductive and endothelioid cells
• Periodontal ligament stem cells (PDLSCs)
• Periodontal ligament - contains stem cells which have the potential to form periodontal structures such as cementum and ligament
• from the roots of extracted teeth
• In vitro-differentiate into osteoblasts, cementoblasts,
• and adipocytes.
• In vivo, after transplantation into mice, structures resembling bone, cementum, cartilage, and PDL have been found.
• Dental follicle stem cells (DFSCs)
• The dental follicle plays a major role in the genesis of cementum, periodontal ligament, and alveolar bone.
• isolated from the follicles of impacted third molars
• in vitro exhibit characteristics of cementoblasts and osteoblasts-can differentiate neurally.
• In vivo, tissue similar to dental cementum and differentiation into PDL progenitor cells
• Stem cells from the dental apical papilla (SCAPs)
• SCAPs - stem cells from the apical part of the papilla,
• a precursor tissue of the dental pulp.
•  Impacted third molars
• In vitro, SCAPs -differentiate osteogenically, odontogenically, and adipogenically.
• In vivo, SCAPs -differentiate into odontonblasts and osteoblasts.
• Non-dental stem cells
• Human bone marrow-bone marrow derived mesenchymal stem cells (BMSCs) can replicate themselves and, in experiments, be differentiated into osteoblasts, myoblasts, adipocytes, and neuron-like cells
• In humans, BMSCs -used therapeutically in bone augmentation by sinus lifts
• -minimally invasively harvested from the iliac crest and inserted into the maxillary sinus on a carrier.
• MBMSCs -(mandibular bone marrow stem cells)
• -possess a high osteogenic potency
• Mesenchymal cells can be isolated from odontomas and differentiated into dental hard tissue, such as dentin
• Other sources :
• From umbilical cord blood
• cartilage
• the cornea
• mammary glands
• adipose tissue
• Renal stem cells
• Medical research- multipotent neural stem cells
•  from areas such as the hippocampus and subventricular zone
• Dermal multipotent cells -differentiated to odontoblasts in embryonic tooth-bud medium
• Dental Stem cell markers
• Identify,characterize, and isolate stem cells.
• STRO-1, a trypsin-resistant cell-surface antigen- most common-early surface markers of mesenchymal stem cells
• STRO-4, binds to heat shock protein–90 beta of multipotent MSCs
• The osteoblast marker osteocalcin -a stem cell marker of DPSCs
• The neural marker nestin on dental stem cells
• Conclusion
• For dentistry, stem cell biology and tissue engineering are of great interest.
• A great deal of research must be done before it is possible to cultivat eentire teeth as natural, autologous tooth replacements

 

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