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Stem cell
Therapy for
Xerostomia
Srija. Ch
SALIVA
It helps to speak , swallow , masticate , taste food and maintain healthy oral cavity.
In a healthy individual, production of saliva is 0.75-1.5 liters/ day (approx.)
3MAJORGLANDS
PAROTID
SUBMANDIBULAR
SUBLINGUAL
SALIVARY GLANDS
• There are 800-1000 minor salivary
glands
• In oral cavity,
70% of saliva – Submandibular
5% - Sublingual
• From ectoderm – Parotid
• From Endoderm – Submandibular and
Sublingual
65-75%
20%
7-8 %
<10 %
CONTRIBUTION OF SALIVA
Submandibular gland Parotid gland Sublingual gland Minor
The 3
main
type
of
cells
• Serous producing
acinar cells:
Pyradmidal
morphology and are
joined to form
spheroidal shapes.
• Mucous producing
acinar cells:
Cuboidal in shape
and are grouped
together to form
tubules.
• Myoepithelial cells:
Located near the
ductal openings and
contracts the ducts
for secretion
•Xerostomia is the subjective feeling of oral dryness,
which is often associated with hypofunction of the
salivary glands.
•It may be associated with a change in the composition
of saliva, or reduced salivary flow (hyposalivation).
•Also known as:
- Cotton mouth
- Des (desert like)
- Drough mouth
XEROSTOMIA
CAUSES
1. IATROGENIC ORIGIN ( Radiation
therapy for head and neck cancers )
2. Developmental origin ( Salivary
gland aplasia )
3. Water / metabolite loss ( impaired
intake, haemorrhage, diarrhoea,
vomiting )
4. Local factors ( smoking, mouth
breathing )
5. Systemic diseases
• HIV
• DM and DI
• HEP-C
6. Side effects of medications (
Diazepam, Atropine )
TREATMENT
1. Chew sugar free gum
2. Limit you caffeine intake
3. Don’t use mouth washes that
contain Alcohol
4. Stop all tobacco use
5. Sip water regularly
6. Saliva substitutes
7. Avoid mouth breathing
8. Avoid excess use of anti-histamines
and decongestants
9. Stem cell therapy
PROPERTIES
1. Self renewal
2. Potency
STEM CELL THERAPY
Use of stem cells to treat or prevent a disease
or condition.
STEM CELL THERAPY
There are different sources of stem cells
Rodent SSPCSs :
o Isolated cells were cultured
o 7th day – growth factors
o expression of ductal, acinar and myoepitheilial cells.
o salispheres with proliferating cells are seen.
o 70% recovery
Salivary gland- derived
stem cells:
Isolated from parotid
or submandibular or a
combination of both.
They display MSC like
characteristics
 After 60 days - twice
when compared to the
untreated ones.
Acinar cell surface
area
They are multipotent stem
cells capable of differentiating
into many types of cells.
They have a high potential to
repair damaged tissues and
low immunogenicity.
Both for in vivo and in vitro
as well as clinical treatment of
various diseases.
Mesenchymal stem cells
Mesenchymal stem cell
implantation
•The intravenous injection of MSCs reduced
lymphocytic infiltrate and inflammation of salivary
glands.
•It also preserved the saliva flow rate – 2 fold higher
•Reduced cell apoptosis and increased microvessel
density.
•Additional tissue repair and regeneration was
observed when given with CFA.
ADIPOSE-DERIVED MSC
 Readily available, contributes to angiogenesis secretes
cytokines and growth factors.
After precutaneous administration, saliva flow rate
increased by 75%
The ADSC treatment displayed group had more acinar
cells and blood endothelial cells.
Human amniotic epithelial cells:
Derived from the top most layer of the amniotic membrane
during c-section.
Intra-glandularly injected hAECs were capable of
differentiating into acinar cells and restoring saliva.
The salivary flow rate at 30 days was restored to 48%
Bioengineered organ germ
Timeline:
Isolation
of stem
cells.
Day 1:
epithelial-
mesenchymal
interactions
developed to an
initial bud
stage.
Day 3:
Branching
followed by
stalk
elongation
and cleft
formation.
After 3 days:
Accumulation
of saliva in the
ducts
Transplantation
They are developed in vivo with the correct
connection to the recipient parotid glandular duct.
It is detected by fluorescence.
Histological analysis is done by H&E and PAS
ASSESSMENT OF SALIVA
The acinar cell differentiation and acinar cell formation is analysed.
In response to the nerve stimulations.
In response to citrate stimulation by citrate.
By analyzing the protein components, such as amylase.
FUNCTIONAL RECOVERY OF
SWALLOWING AND SURVIVAL
Among salivary
functions, the
swallowing
function is
critical for
nutrition and
reducing the risk
of aspiration.
It is investigated
by the analyzing
the relationship
between body
weight and
survival of
salivary gland
defect mice.
After the
transplantation
of the
bioengineered
gland, the
symptoms
caused by the
swallowing
dysfunction are
decreased.
The recovery is
done after 4
days which is
the amount of
time required by
the
development of
acini.
CONCLUSION:
When the damage is beyond repair, there is a need for
methods to salvage the RT damage that has occurred.
Stem cell therapy does not provide a symptomatic
treatment but rather treats the underlying cause: a lack of
functional acinar cells.
More research should be done regarding the stem cell
therapy for the complete and a better treatment for these
diseases
Stem cell therapy for xerostomia

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Stem cell therapy for xerostomia

  • 2. SALIVA It helps to speak , swallow , masticate , taste food and maintain healthy oral cavity. In a healthy individual, production of saliva is 0.75-1.5 liters/ day (approx.)
  • 3. 3MAJORGLANDS PAROTID SUBMANDIBULAR SUBLINGUAL SALIVARY GLANDS • There are 800-1000 minor salivary glands • In oral cavity, 70% of saliva – Submandibular 5% - Sublingual • From ectoderm – Parotid • From Endoderm – Submandibular and Sublingual 65-75% 20% 7-8 % <10 % CONTRIBUTION OF SALIVA Submandibular gland Parotid gland Sublingual gland Minor
  • 4. The 3 main type of cells • Serous producing acinar cells: Pyradmidal morphology and are joined to form spheroidal shapes. • Mucous producing acinar cells: Cuboidal in shape and are grouped together to form tubules. • Myoepithelial cells: Located near the ductal openings and contracts the ducts for secretion
  • 5. •Xerostomia is the subjective feeling of oral dryness, which is often associated with hypofunction of the salivary glands. •It may be associated with a change in the composition of saliva, or reduced salivary flow (hyposalivation). •Also known as: - Cotton mouth - Des (desert like) - Drough mouth XEROSTOMIA
  • 6. CAUSES 1. IATROGENIC ORIGIN ( Radiation therapy for head and neck cancers ) 2. Developmental origin ( Salivary gland aplasia ) 3. Water / metabolite loss ( impaired intake, haemorrhage, diarrhoea, vomiting ) 4. Local factors ( smoking, mouth breathing ) 5. Systemic diseases • HIV • DM and DI • HEP-C 6. Side effects of medications ( Diazepam, Atropine ) TREATMENT 1. Chew sugar free gum 2. Limit you caffeine intake 3. Don’t use mouth washes that contain Alcohol 4. Stop all tobacco use 5. Sip water regularly 6. Saliva substitutes 7. Avoid mouth breathing 8. Avoid excess use of anti-histamines and decongestants 9. Stem cell therapy
  • 7. PROPERTIES 1. Self renewal 2. Potency STEM CELL THERAPY Use of stem cells to treat or prevent a disease or condition.
  • 8. STEM CELL THERAPY There are different sources of stem cells Rodent SSPCSs : o Isolated cells were cultured o 7th day – growth factors o expression of ductal, acinar and myoepitheilial cells. o salispheres with proliferating cells are seen. o 70% recovery
  • 9. Salivary gland- derived stem cells: Isolated from parotid or submandibular or a combination of both. They display MSC like characteristics  After 60 days - twice when compared to the untreated ones. Acinar cell surface area
  • 10. They are multipotent stem cells capable of differentiating into many types of cells. They have a high potential to repair damaged tissues and low immunogenicity. Both for in vivo and in vitro as well as clinical treatment of various diseases. Mesenchymal stem cells
  • 11. Mesenchymal stem cell implantation •The intravenous injection of MSCs reduced lymphocytic infiltrate and inflammation of salivary glands. •It also preserved the saliva flow rate – 2 fold higher •Reduced cell apoptosis and increased microvessel density. •Additional tissue repair and regeneration was observed when given with CFA.
  • 12. ADIPOSE-DERIVED MSC  Readily available, contributes to angiogenesis secretes cytokines and growth factors. After precutaneous administration, saliva flow rate increased by 75% The ADSC treatment displayed group had more acinar cells and blood endothelial cells.
  • 13. Human amniotic epithelial cells: Derived from the top most layer of the amniotic membrane during c-section. Intra-glandularly injected hAECs were capable of differentiating into acinar cells and restoring saliva. The salivary flow rate at 30 days was restored to 48%
  • 14. Bioengineered organ germ Timeline: Isolation of stem cells. Day 1: epithelial- mesenchymal interactions developed to an initial bud stage. Day 3: Branching followed by stalk elongation and cleft formation. After 3 days: Accumulation of saliva in the ducts
  • 15.
  • 16. Transplantation They are developed in vivo with the correct connection to the recipient parotid glandular duct. It is detected by fluorescence. Histological analysis is done by H&E and PAS
  • 17. ASSESSMENT OF SALIVA The acinar cell differentiation and acinar cell formation is analysed. In response to the nerve stimulations. In response to citrate stimulation by citrate. By analyzing the protein components, such as amylase.
  • 18. FUNCTIONAL RECOVERY OF SWALLOWING AND SURVIVAL Among salivary functions, the swallowing function is critical for nutrition and reducing the risk of aspiration. It is investigated by the analyzing the relationship between body weight and survival of salivary gland defect mice. After the transplantation of the bioengineered gland, the symptoms caused by the swallowing dysfunction are decreased. The recovery is done after 4 days which is the amount of time required by the development of acini.
  • 19. CONCLUSION: When the damage is beyond repair, there is a need for methods to salvage the RT damage that has occurred. Stem cell therapy does not provide a symptomatic treatment but rather treats the underlying cause: a lack of functional acinar cells. More research should be done regarding the stem cell therapy for the complete and a better treatment for these diseases

Hinweis der Redaktion

  1. Epidermal and hepatocyte growth factors After mechanical and enzymatic digestion, aggregates of cells – salispheres Acinar by alpha amylase Ductal cells ( cytokeratins 7 and 14) Ductal like in vivo functionality is seen after transplantation
  2. MSC like characteristics – adipogenic, osteogenic and chondrogenic in induction media Positive for MSC markers and –ve for HSC markers Both glands – in vivo also Intra glandular transplantation- 3rd day- Ductal structures
  3. Differentiating into chondrocytes, adipocytes, osteoblasts and acinar cells.
  4. In relation with sjogrens syndrome Can be given with CFA ( Complete Freund’s adjuvant), regen potential inc Allogenic MSCs both prevented and reduced inf response and with less adverse effects
  5. Derivation by trypsinization. Can differntiate into the cells of three germ layers such as osteocytes, adipocytes, neurons, hepatocytes, cardiomyocytes and pancreatic cells
  6. Mention recent bioengineering aproaches – muscarinic receptors agonists like pilocarpine and cevimeline but they have side effec
  7. Gep: green fluorescence protein GEP +ve and -ve
  8. By membrane water channel protein Nerve stimulation : pilocarpine (parasympathetic drug: inc, inhibited by Achs) SalivaBio Oral Swab (SOS) Saliva Collection Method Citrate: afferent and efferent stimulation Comparable to normal salivary gland
  9. After extracting the glands, mice die after 5 days even with sufficient food, because of swallowing dysfunction. BW is initially decreased within 2 days of transplantation.