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DENTAL STEM CELLS

PREPARED BY :   GHOLAMI HAMED
Stem cells are the body's "master" cells that
regenerate the body's many cells, tissues, and
organs. Most cells in your body can only make new
cells of the same type - blood cells make blood
cells, skin cells make more skins cells and so on.

Stem cells are unique not only because they can
turn into many different types of cells - a stem cell
might create blood, kidney, heart, or bone for
example - but also because they can divide many
more times than other cells.
There are two broad types of stem cells: embryonic
stem cells and adult stem cells.

While there has been much debate on the ethical
issues surrounding the use of embryonic stem cells,
adult stem cells are free of this controversy and only
adult stem cells, to date, have been used to treat
people.
The most commonly known source of adult stem
cells is bone marrow, which contains both
hematopoietic stem cells (also found in cord blood)
and mesenchymal stem cells (also found in teeth).
DENTAL STEM CELLS AND TRANSFER FACTORS

  Tooth infections or injuries involving dental pulp are
  treated routinely by root canal therapy. Endodontically
  treated teeth are devitalized, susceptible to re-infections,
  fractures, and subsequent tooth loss. Here, we report
  regeneration of dental-pulp-like tissue by cell homing and
  without cell transplantation. Upon in vivo implantation of
  endodontically treated real-size, native human teeth in
  mouse dorsum for the tested 3 weeks, delivery of basic
  fibroblast growth factor and/or vascular endothelial growth
  factor (bFGF and/or VEGF) yielded re-cellularized and
  revascularized connective tissue that integrated to native
  dentinal wall in root canals
Further, combined delivery of bFGF, VEGF, or platelet-
derived growth factor (PDGF) with a basal set of nerve
growth factor (NGF) and bone morphogenetic protein-7
(BMP7) generated cellularized and vascularized tissues
positive of VEGF antibody staining and apparent neo-dentin
formation over the surface of native dentinal wall in some,
but not all, endodontically treated teeth. Newly formed
dental pulp tissue appeared dense with disconnected cells
surrounded by extracellular matrix. Erythrocyte-filled blood
vessels were present with endothelial-like cell lining.
Reconstructed, multiple microscopic images showed
complete fill of dental-pulp-like tissue in the entire root
canal from root apex to pulp chamber with tissue
integration to dentinal wall upon delivery of bFGF, VEGF,
or PDGF with a basal set of NGF and BMP7. Quantitative
ELISA showed that combinatory delivery of bFGF, VEGF,
or PDGF with basal NGF and BMP7 elaborated von
Willerbrand factor, dentin sialoprotein, and NGF. These
findings represent the first demonstration of regenerated
dental-pulp-like tissue in endodontically treated root
canals of real-size, native human teeth
The present chemotaxis-based approach has potent cell
homing effects for re-cellularization and revascularization
in endodontically treated root canals in vivo, although in
an ectopic model. Regeneration of dental pulp by cell
homing, rather than cell delivery, may accelerate clinical
translation.
Anatomy of dental pulp

The dental pulp is the part in the center of a tooth made up
of living soft tissue and cells called odontoblasts. The central
region of the coronal and radicular pulp contains large nerve
trunks and blood vessels. This area is lined peripherally by a
specialized odontogenic area which has three layers which
are (from innermost to outermost): cell rich zone, cell free
zone and odontoblastic layer.
During tooth formation, interactions between
epithelial and dental papilla cells promote tooth
morphogenesis by stimulating a subpopulation of
mesenchymal cells to differentiate into
odontoblasts, which in turn form primary dentin.
These odontoblasts are thought to arise from the
proliferation and differentiation of a precursor
population, residing somewhere within the pulp
tissue
Types of dental stem cells:

At least five different types of postnatal
mesenchymal stem cells have been reported to
differentiated to odontoblast-like cells.
1.dental pulp stem cells(DPSC)
2.dental pulp of human exfolliated deciduous
teeth(SHED)
3.stem cells of apicall papilla(SCAP)
4.Dental follicle progenitor cells(DFPC)
5.Bone marrow-derived mesenchymal stem
cells(BMMCS)
1.Dental pulp stem cells:

 (DPSCs) represent a kind of adult cell colony which has the
potent capacity of self-renewing and multilineage differentiation.
The exact origin of DPSCs has not been fully determined and
these stem cells seem to be the source of odontoblasts that
contribute to the formation of dentin-pulp complex. Recently,
achievements obtained from stem cell biology and tooth
regeneration have enabled us to contemplate the potential
applications of DPSCs. Some studies have proved that DPSCs
are capable of producing dental tissues in vivo including dentin,
pulp, and crown-like structures. Whereas other investigations
have shown that these stem cells can bring about the formation
of bone-like tissues. Theoretically, a bio-tooth made from
autogenous DPSCs should be the best choice for clinical tooth
reconstruction.
2.Dental pulp of human exfolliated
deciduous teeth

 contains multipotent stem cells
from humanexfoliated deciduous teeth (SHED). were
identified to be a population of highly proliferative, clonogenic
cells capable of differentiating into a variety of cell types
including neural cells, adipocytes, and odontoblasts. Thus,
exfoliated teeth may be an unexpected unique resource for
stem-cell therapies including autologous stem-cell
transplantation and tissue engineering.
3.Stem cells of apical papilla

A unique population of dental stem cells known as
stem cells from the root apical papilla (SCAP) is
located at the tips of growing tooth roots . The apical
papilla tissue is only present during root development
before the tooth erupts into the oral cavity . SCAP
have the capacity to differentiate into odontoblasts
and adipocytes .These cells are CD24+ but
expression is downregulated upon odontogenic
differentiation in vitro coincident with alkaline
phosphatase upregulation
4.Dental follicle progenitor cells:

The dental follicle is a loose ectomesenchyme-
derived connective tissue sac surrounding the
enamel organ and the dental papilla of the
developing tooth germ before eruption . It is
believed to contain progenitors for cementoblasts,
PDL and osteoblasts. Dental follicle cells (DFC)
form the PDL by differentiating into PDL fibroblasts
that secrete collagen and interact with fibres on the
surfaces of adjacent bone and cementum
5. bone marrow derrived cells:

Bone marrow-derived cells (BMDCs) have the
potential to engraft into several tissues after
injury, but whether they can become dental
tissue-specific progenitor cells under normal
conditions and the relationship of these cells to
the tissue-resident cells are unknown.
 bone marrow progenitor cells communicate with
dental tissues and become tissue-specific
mesenchymal progenitor cells to maintain tissue
homeostasis.
INDICATION

1.Dental tissue repair:

 dental stem cells are currently considered to offer potential for
tissue regeneration. These include the obvious uses of cells to
 repair damaged tooth tissues such as dentine, periodontal
ligament and dental pulp Even enamel tissue engineering has
been suggested as well as the use of dental stem cells as
sources of cells to facilitate repair of non-dental tissues such
as bone and nerves
2.Periodontal regeneration:

The periodontium is a set of specialized tissues that
surround and support the teeth to maintain them in the jaw.
Periodontitis is an inflammatory disease that affects the
periodontium and results in irreversible loss of connective
tissue attachment and the supporting alveolar bone. The
challenge for cell-based replacement of a functional
periodontium is therefore to form new ligament and bone,
and to ensure that the appropriate connections are made
between these tissues, as well as between the bone and
tooth root. . One aim of current research is to use different
populations of dental stem cells to replicate the key events
in periodontal development both temporally and spatially, so
that healing can occur in a sequential manner to regenerate
the periodontium
4.Regeneration of dental pulp in
immature tooth

Dental pulp needs to be removed when it becomes
infected, and this is particularly problematic for root pulp
that requires endodontic (root canal) treatment. The
restoration of tooth pulp is thus a much sought after goal
in dentistry because the current practice of replacing
infected pulp with inorganic materials (cements) results in
a devitalized (dead) tooth. A recent study demonstrated de
novo regeneration of dental pulp in emptied root canal
space using dental stem cells .
5.Whole tooth regeneration:

The current state of the art in tooth replacement is a
dental implant that involves screwing a threaded metal
rod into a predrilled hole in the bone, which is then
capped with a plastic or ceramic crown. Implant use
requires a minimum amount of bone to be present.
Because these implants attach directly to the bone
without the PDL ‘shock absorber’, the forces of
mastication are transmitted directly to the bone, which is
one reason implants can fail. In cases where there is
insufficient bone for implants, such as tooth loss as a
consequence of the bone loss that occurs in
postmenopausal osteoporosis, implants have to be
preceded by bone grafts. The ultimate goal in dentistry
is to have a method to biologically replace lost teeth; in
Techniques:
a.The idea is to take adult stem cells, treat them
in a cell culture so they would be programmed to
develop into teeth and then transplanted into the
patients jaw where the gap is. Then a
replacement tooth grows just as happens when
humans grow their original adult teeth. It is
thought it would then take two to three months
for the tooth to fully develop. The cost should not
be more than existing treatments making it an
attractive alternative to other technologies such
as implants and dentures.
b.The tooth bud is then implanted in the jaw and
the gum stitched or sealed with a clinical "glue".
They have not started human clinical trials yet,
however they expect the procedure to be less
invasive than a tooth extraction and the
requirements for post-procedure care would be
similar. After implantation it takes the tooth about 3
weeks to set in the jaw of a mouse. As long as the
tooth is not under heavy load, it sets well.
The technology to grow replacement teeth could
mean the end of dentures
Advantages
1.It provides medical benefits in the fields of therapeutic
cloning and regenerative medicine.
2.It provides great potential for discovering treatments
and cures to a plethora of diseases including Parkinson's
disease, schizophrenia, Alzheimer's disease, cancer,
spinal cord injuries, diabetes and many outhers
3.Regenerated pulp can re-build a damaged tooth from
the inside

4• Tooth with a regenerated pulp will require markedly
smaller restorations

5• Tooth with a regenerated pulp may uphold the
proprioceptive function of the tooth
Disadvantages:

1.The use of embryonic stem cells involves the
destruction of blastocysts formed from laboratory-
fertilized human eggs. For those people who believe that
life begins at conception, the blastocyst is a human life
and to destroy it is immoral and unacceptable.
2.Like any other new technology, it is also completely
unknown what the long-term effects of such an
interference with nature could materialize.
3. These are derived from embryos that are not a
patient's own and the patient's body may reject them.
Summary

Tooth Stem Cells Therapeutic Potential
The ultimate goal of tooth regeneration is to replace
the lost teeth. Stem cell-based tooth engineering is
deemed as a promising approach to the making of
a biological tooth (bio-tooth). Dental pulp stem cells
(DPSCs) represent a kind of adult cell colony which
has the potent capacity of self-renewing and
multilineage differentiation. A bio-tooth made from
autogenous DPSCs should be the best choice for
clinical tooth reconstruction.
Electronic references:

http://www.squidoo.com/stem-cells-dentistry
http://www.buzzle.com
http://news.healingwell.com
http://www.ibridgenetwork.org
http://www.ncbi.nlm.nih
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Dental stem cells

  • 1. DENTAL STEM CELLS PREPARED BY : GHOLAMI HAMED
  • 2. Stem cells are the body's "master" cells that regenerate the body's many cells, tissues, and organs. Most cells in your body can only make new cells of the same type - blood cells make blood cells, skin cells make more skins cells and so on. Stem cells are unique not only because they can turn into many different types of cells - a stem cell might create blood, kidney, heart, or bone for example - but also because they can divide many more times than other cells.
  • 3. There are two broad types of stem cells: embryonic stem cells and adult stem cells. While there has been much debate on the ethical issues surrounding the use of embryonic stem cells, adult stem cells are free of this controversy and only adult stem cells, to date, have been used to treat people.
  • 4. The most commonly known source of adult stem cells is bone marrow, which contains both hematopoietic stem cells (also found in cord blood) and mesenchymal stem cells (also found in teeth).
  • 5. DENTAL STEM CELLS AND TRANSFER FACTORS Tooth infections or injuries involving dental pulp are treated routinely by root canal therapy. Endodontically treated teeth are devitalized, susceptible to re-infections, fractures, and subsequent tooth loss. Here, we report regeneration of dental-pulp-like tissue by cell homing and without cell transplantation. Upon in vivo implantation of endodontically treated real-size, native human teeth in mouse dorsum for the tested 3 weeks, delivery of basic fibroblast growth factor and/or vascular endothelial growth factor (bFGF and/or VEGF) yielded re-cellularized and revascularized connective tissue that integrated to native dentinal wall in root canals
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  • 7. Further, combined delivery of bFGF, VEGF, or platelet- derived growth factor (PDGF) with a basal set of nerve growth factor (NGF) and bone morphogenetic protein-7 (BMP7) generated cellularized and vascularized tissues positive of VEGF antibody staining and apparent neo-dentin formation over the surface of native dentinal wall in some, but not all, endodontically treated teeth. Newly formed dental pulp tissue appeared dense with disconnected cells surrounded by extracellular matrix. Erythrocyte-filled blood vessels were present with endothelial-like cell lining.
  • 8. Reconstructed, multiple microscopic images showed complete fill of dental-pulp-like tissue in the entire root canal from root apex to pulp chamber with tissue integration to dentinal wall upon delivery of bFGF, VEGF, or PDGF with a basal set of NGF and BMP7. Quantitative ELISA showed that combinatory delivery of bFGF, VEGF, or PDGF with basal NGF and BMP7 elaborated von Willerbrand factor, dentin sialoprotein, and NGF. These findings represent the first demonstration of regenerated dental-pulp-like tissue in endodontically treated root canals of real-size, native human teeth
  • 9. The present chemotaxis-based approach has potent cell homing effects for re-cellularization and revascularization in endodontically treated root canals in vivo, although in an ectopic model. Regeneration of dental pulp by cell homing, rather than cell delivery, may accelerate clinical translation.
  • 10. Anatomy of dental pulp The dental pulp is the part in the center of a tooth made up of living soft tissue and cells called odontoblasts. The central region of the coronal and radicular pulp contains large nerve trunks and blood vessels. This area is lined peripherally by a specialized odontogenic area which has three layers which are (from innermost to outermost): cell rich zone, cell free zone and odontoblastic layer.
  • 11. During tooth formation, interactions between epithelial and dental papilla cells promote tooth morphogenesis by stimulating a subpopulation of mesenchymal cells to differentiate into odontoblasts, which in turn form primary dentin. These odontoblasts are thought to arise from the proliferation and differentiation of a precursor population, residing somewhere within the pulp tissue
  • 12. Types of dental stem cells: At least five different types of postnatal mesenchymal stem cells have been reported to differentiated to odontoblast-like cells.
  • 13. 1.dental pulp stem cells(DPSC) 2.dental pulp of human exfolliated deciduous teeth(SHED) 3.stem cells of apicall papilla(SCAP) 4.Dental follicle progenitor cells(DFPC) 5.Bone marrow-derived mesenchymal stem cells(BMMCS)
  • 14. 1.Dental pulp stem cells: (DPSCs) represent a kind of adult cell colony which has the potent capacity of self-renewing and multilineage differentiation. The exact origin of DPSCs has not been fully determined and these stem cells seem to be the source of odontoblasts that contribute to the formation of dentin-pulp complex. Recently, achievements obtained from stem cell biology and tooth regeneration have enabled us to contemplate the potential applications of DPSCs. Some studies have proved that DPSCs are capable of producing dental tissues in vivo including dentin, pulp, and crown-like structures. Whereas other investigations have shown that these stem cells can bring about the formation of bone-like tissues. Theoretically, a bio-tooth made from autogenous DPSCs should be the best choice for clinical tooth reconstruction.
  • 15. 2.Dental pulp of human exfolliated deciduous teeth contains multipotent stem cells from humanexfoliated deciduous teeth (SHED). were identified to be a population of highly proliferative, clonogenic cells capable of differentiating into a variety of cell types including neural cells, adipocytes, and odontoblasts. Thus, exfoliated teeth may be an unexpected unique resource for stem-cell therapies including autologous stem-cell transplantation and tissue engineering.
  • 16. 3.Stem cells of apical papilla A unique population of dental stem cells known as stem cells from the root apical papilla (SCAP) is located at the tips of growing tooth roots . The apical papilla tissue is only present during root development before the tooth erupts into the oral cavity . SCAP have the capacity to differentiate into odontoblasts and adipocytes .These cells are CD24+ but expression is downregulated upon odontogenic differentiation in vitro coincident with alkaline phosphatase upregulation
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  • 18. 4.Dental follicle progenitor cells: The dental follicle is a loose ectomesenchyme- derived connective tissue sac surrounding the enamel organ and the dental papilla of the developing tooth germ before eruption . It is believed to contain progenitors for cementoblasts, PDL and osteoblasts. Dental follicle cells (DFC) form the PDL by differentiating into PDL fibroblasts that secrete collagen and interact with fibres on the surfaces of adjacent bone and cementum
  • 19. 5. bone marrow derrived cells: Bone marrow-derived cells (BMDCs) have the potential to engraft into several tissues after injury, but whether they can become dental tissue-specific progenitor cells under normal conditions and the relationship of these cells to the tissue-resident cells are unknown. bone marrow progenitor cells communicate with dental tissues and become tissue-specific mesenchymal progenitor cells to maintain tissue homeostasis.
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  • 22. INDICATION 1.Dental tissue repair: dental stem cells are currently considered to offer potential for tissue regeneration. These include the obvious uses of cells to repair damaged tooth tissues such as dentine, periodontal ligament and dental pulp Even enamel tissue engineering has been suggested as well as the use of dental stem cells as sources of cells to facilitate repair of non-dental tissues such as bone and nerves
  • 23. 2.Periodontal regeneration: The periodontium is a set of specialized tissues that surround and support the teeth to maintain them in the jaw. Periodontitis is an inflammatory disease that affects the periodontium and results in irreversible loss of connective tissue attachment and the supporting alveolar bone. The challenge for cell-based replacement of a functional periodontium is therefore to form new ligament and bone, and to ensure that the appropriate connections are made between these tissues, as well as between the bone and tooth root. . One aim of current research is to use different populations of dental stem cells to replicate the key events in periodontal development both temporally and spatially, so that healing can occur in a sequential manner to regenerate the periodontium
  • 24. 4.Regeneration of dental pulp in immature tooth Dental pulp needs to be removed when it becomes infected, and this is particularly problematic for root pulp that requires endodontic (root canal) treatment. The restoration of tooth pulp is thus a much sought after goal in dentistry because the current practice of replacing infected pulp with inorganic materials (cements) results in a devitalized (dead) tooth. A recent study demonstrated de novo regeneration of dental pulp in emptied root canal space using dental stem cells .
  • 25. 5.Whole tooth regeneration: The current state of the art in tooth replacement is a dental implant that involves screwing a threaded metal rod into a predrilled hole in the bone, which is then capped with a plastic or ceramic crown. Implant use requires a minimum amount of bone to be present. Because these implants attach directly to the bone without the PDL ‘shock absorber’, the forces of mastication are transmitted directly to the bone, which is one reason implants can fail. In cases where there is insufficient bone for implants, such as tooth loss as a consequence of the bone loss that occurs in postmenopausal osteoporosis, implants have to be preceded by bone grafts. The ultimate goal in dentistry is to have a method to biologically replace lost teeth; in
  • 26. Techniques: a.The idea is to take adult stem cells, treat them in a cell culture so they would be programmed to develop into teeth and then transplanted into the patients jaw where the gap is. Then a replacement tooth grows just as happens when humans grow their original adult teeth. It is thought it would then take two to three months for the tooth to fully develop. The cost should not be more than existing treatments making it an attractive alternative to other technologies such as implants and dentures.
  • 27. b.The tooth bud is then implanted in the jaw and the gum stitched or sealed with a clinical "glue". They have not started human clinical trials yet, however they expect the procedure to be less invasive than a tooth extraction and the requirements for post-procedure care would be similar. After implantation it takes the tooth about 3 weeks to set in the jaw of a mouse. As long as the tooth is not under heavy load, it sets well. The technology to grow replacement teeth could mean the end of dentures
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  • 30. Advantages 1.It provides medical benefits in the fields of therapeutic cloning and regenerative medicine. 2.It provides great potential for discovering treatments and cures to a plethora of diseases including Parkinson's disease, schizophrenia, Alzheimer's disease, cancer, spinal cord injuries, diabetes and many outhers 3.Regenerated pulp can re-build a damaged tooth from the inside 4• Tooth with a regenerated pulp will require markedly smaller restorations 5• Tooth with a regenerated pulp may uphold the proprioceptive function of the tooth
  • 31. Disadvantages: 1.The use of embryonic stem cells involves the destruction of blastocysts formed from laboratory- fertilized human eggs. For those people who believe that life begins at conception, the blastocyst is a human life and to destroy it is immoral and unacceptable. 2.Like any other new technology, it is also completely unknown what the long-term effects of such an interference with nature could materialize. 3. These are derived from embryos that are not a patient's own and the patient's body may reject them.
  • 32. Summary Tooth Stem Cells Therapeutic Potential The ultimate goal of tooth regeneration is to replace the lost teeth. Stem cell-based tooth engineering is deemed as a promising approach to the making of a biological tooth (bio-tooth). Dental pulp stem cells (DPSCs) represent a kind of adult cell colony which has the potent capacity of self-renewing and multilineage differentiation. A bio-tooth made from autogenous DPSCs should be the best choice for clinical tooth reconstruction.