stems cells and their dental application

what is a stem cell?

undifferentiated cell with ability to divide and differentiate

• divide (symmetric division): self-renewal: stem cell →stem cell: like 2 daughter cells

• differentiate (asymmetric): potency stem cell to specialized cell

3 types of stem cells

embryonic, adult, iPS

what are embryonic stem cells?

cells derived from undifferentiated inner cell mass of blastocyst

what are adult stem cells?

aka post natal stem cells

undifferentiated cells found among differentiated cells of specific tissue

*mesenchymal cells are adult stem cells that form osteoblasts (bone cells), chondrocytes (cartilage), myocytes (muscle), adipocytes (fat cells)

what are iPS cells?

induced pluripotent stem cells

five differentiation potential of stem cells

totipotent, pluripotent, multipotent, oligopotent, unipotent

what does totipotent mean?

capable of differentiation and forming a new indiv

ex: fertilized egg (zygote)

what does pluripotent mean?

capable of giving rise to several different cell types

ex: embryonic stem cells, iPS cell

what does multipotent mean?

can differentiation into range of cell types in the body

ex: mesenchymal stem cells (adult stem cells)

what is the most relevant stem cell for dentistry?

mutlipotent

what does oligopotent mean?

can only differentiate into close-related cell types

ex: hematopoietic stem cell (adult stem cell)

what does unipotent mean?

can only change into one cell type in the body (no differentiation)

ex: muscle stem cells

*busch law about stem cells:

Executive Order 13435 to promote research on alternative sources of pluripotent stem cells that do not involve the destruction of embryos: federal funding only for research on existing embryonic stem cell lines derived before the policy's announcement.

• Embryonic stem cells are usually derived from early-stage embryos, and obtaining them typically involves destroying the embryo: younger is better than older! (stem cells)

• Some worry that allowing embryonic stem cell research could lead to other ethically questionable practices, such as cloning or the creation of embryos specifically for research purposes.

• commercialization of embryonic stem cell research raises ethical questions around commodifying human life. There’s concern about the risk of exploiting women for egg donations, which could happen if the demand for embryos increases.

four differences between embryonic stem cells vs adult stem cells:

	embryonic	adult
differentiation potential:	pluripotent	multipotent
ethical concern:	destruction of blastocyst	destruction of blastocyst
proliferative capacity:	high/divide indefinitely	limited/limited expansion
risk of tumor formation:	high	low

blastocyst

a ball of cells that forms early in a pregnancy, about five to six days after a sperm fertilizes an egg

what are the three components of the tissue engineering triangle?

biological factors, scaffolds, cells

biological factors of tissue engineering for dental pulp regeneration?

DPSCs, SHED, SCAP

scaffolds of tissue engineering for dental pulp regeneration?

scaffold-free, collagen, hydrogel, synthetic polymer, injectable

biological factors of tissue engineering for dental pulp regeneration?

TGF-β1 and BMP-2 (bone morphogenetic proteins)

with extra stem cells (exogenous and endogenous) you can:

do cell transplant

without extra stem cells (having endogenous cells only):

cell homing: cells migrate to their target tissue sites before they proliferate

what are the three cell source types?

autologous: own

allogenic: not own

syngeneic: similar enough to be transplanted (identical twins)

what is stem cell niche?

specialized microenvironment within tissues where stem cells reside. then leave and differentiate into specific cells under specific signaling conditions. (retain stemness)

what are bone marrow stem cells?

hematopoietic stem cells (oligopotent) and mesenchymal cells MSCs (multipotent-high diff potential)

bone marrow transplantation: most used stem cell-based therapy

what are adipose-derived stem cells (ASCs)?

stem cells with good differentiation potential (adipocytes, chondrocytes, osteoblast, hepatocytes, endothelial, beta islet, muscle, keratinocytes, neuronal lineages, glial lineages)

plastic adhesion, self-renew, multi-lineage capacity, low immunogenicity

clinical application: wound healing, breast augmentation, cosmetology, hair regeneration, anti-aging

DFCSs

dental follicle stem cells (in dental follicle of tooth bud)

TGPCs

tooth germ progenitor cells (in dental papilla of tooth bud)

DPCS

dental pulp stem cells (in dental pulp of tooth)

SHED

stem cells isolated from exfoliated deciduous teeth (in dental pulp of tooth)

PDLSCs

periodontal ligament stem cells (periodontal ligament of tooth)

• dental follicle-derived mesenchymal cells

• first identified 2004

• multipotent

SCAP

stem cells isolated from the apical papilla (apical papilla of tooth)

what germ layer do teeth come from?

enamel from ectoderm (ameloblasts)

dentin (odontoblasts), pulp, cementum, and the periodontal ligament from mesoderm, neural crest-derived mesenchymal cells

G-MSCs

gingival mesenchymal stem cells

BMSCs

bone marrow stem cells

what are the possible stem cells from adult teeth?

from impacted wisdom: PDLSCs

cracked tooth: DPSCs, SCAP

supernumerary teeth

why chose dental stem cells?

• acquired from medical waste

• minimally invasive isolation method

• immunodulatory and immunosuppressive characteristics

• not limited in dental field: neuron-like, cardiomyocytes, adipocytes, insulin secreting beta cells, hepatocytes

what are the stem cells for regeneration?

• dental tissue-derived iPSCs: “reprogramming” cells, great differentiation potential and dental epithelial stem cell-like cells

• BMSCs

• ADSCs

• HUVEC (human umbilical vein endothelial cells

what is endodontic disease?

infection or inflammation of dental pulp often from caries or trauma

KEY: stem cells differentiate into odontoblasts

affects 65% of individuals; $102 billion US $300 billion worldwide

why is keeping functional pulp so important?

living pulp is required to maintain dentine and tooth sensitivity

what is is the pulp composed of?

• cells

• fibers

• ground substance

• nerves

• blood

• lymphatic vessels

what do dental pulp cells contain?

• odontoblasts = most distinctive

• fibroblasts = most abundant

• defensive cells = macrophages, etc.

• undifferentiated ectomesenchymal or progenitor cells

DPSCs in terms of pulp:

fibroblast-like, neural-crest derived, multipotent in perivascular niches of cell rich zone and pulp core

what are the current therapies for endodontic disease?

reversible pulpitis: indirect and direct pulp capping, pulpoctomy

irreversible pulpitis: root canal, guided pulpal repair (control infection and remove damaged tissue)

dental pulp regeneration purposes and examples:

• purpose: stimulate odotonoblasts to form new dentin deposition to regen dentin-pulp complex. angiogenesis and vasculogenesis and neurogenesis essential for regen

• types: cell homing for partial regen & tiisue engineering for whole

tooth supporting tissues of PDL for regeneration:

bone-PDL-cementum complex, highly-organized collagen fibers insert perpendicularly to cementum and bone

functions of the PDL

transmission of occlusal forces from teeth to bone

• support and stabilize the tooth

• nutritional and sensory

• formative and remodeling

what are the main stem cells for PDL regeneration:

PDLSCs and DPSCs

(BMMSCs, ADSCs, iPSCs too)

methods for PDL regeneration:

• Cell sheet technology involves culturing cells to form a continuous, sheet-like structure without the need for scaffolds allowing for PDL regeneration

• 3D printed fiber: guided scaffold

• clinical trials with GTR and analogous PDLSC sheet with Bio-oss; no clinical significance

• clinical trials with analogous PDLSC in xenogenic bone substitute (XBS) good healing

whole tooth regeneration:

• organ replace therapy-tooth germ

• functionally bioengineered tooth

• bioengineered tooth unt

• decalcified tooth bud

• in vivo cells: human dental pulp cells (hDM), pig dental tooth bud epithelial cells (pDE), HUVECs reseeded to decellularized tooth bud

epithelial-mesenchymal interaction:

epithelial derived and mesenchymal met at EDJ

hair follicles and mammary glands

what are the types of human dental stem cells?

mesenchymal no epithelial

• DPSCs, PDLSCs, SHEDs, SCAPs, DFPCs, hBMSCs

the first tooth regrow medicine:

sept 2024, 30 pts with congenital anodontia, Anti-USAG-1 antibody therapy; Toregem

how are dental stem cells used for non-dental tissue regeneration?

• alveolar bone regeneration: autogenous bone graft

also for:

• bone

• CNS: Alzheimer’s disease, spinal cord injuries

• salivary glands: Sjorgen’s syndrome (autoimmune disorder primarily affecting the body’s moisture-producing glands, leading to symptoms of dryness), irradiated salivaryy glands

• liver tissue

• heart tissue

• eyes (retinal repair) muscles

clinical trials past and current

• dental pulp regeneration

• chronic periodontitis

• periodontal

• alveolar cleft repair

• acute ischemic stroke

cell bank: good manufacturing process GMP grade teeth bank for storing; whole pulp or isolated dental pulp stem cells

exosomes and their role in tissue regeneration:

small extracellular vesicles that contain proteins, lipids, RNAs; good for cell to cell communication

promote repair, modulate immune responses, and stimulate cell proliferation and differentiation: contain no cells, are stable (storage and transport), modifiable lower risk of tumor formation

autologous vs allogenic

• Autologous: Cells or tissues taken from and used in the same person.

  • Advantages: No immune rejection, reduced disease transmission.

  • Uses: Bone marrow transplants, skin grafts, blood transfusions.

• Allogeneic: Cells or tissues taken from a different person of the same species.

  • Advantages: Accessible when patient’s own cells are unavailable.

  • Challenges: Risk of immune rejection, often requires immunosuppressive drugs.

  • Uses: Organ transplants, bone marrow transplants for blood disorders.