Stem Cells & Regenerative Medicine
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Questions and Answers

What is a characteristic ability of induced pluripotent stem cells (iPSCs)?

  • They can differentiate into any cell type found in the body.
  • They can generate cells characteristic of all three germ layers. (correct)
  • They can only generate neurons.
  • They can only be derived from embryonic tissues.
  • What method is used to introduce reprogramming factors into adult cells to create iPSCs?

  • Direct cell fusion
  • Viruses (correct)
  • Chemical treatment
  • Heat shock
  • Which of the following is NOT a source for deriving human iPSCs?

  • Mesenchymal stem cells
  • Cardiac myocytes (correct)
  • Skin keratinocytes
  • Dermal fibroblasts
  • Mesenchymal stem cells (MSCs) were first identified as what type of cells?

    <p>Self-renewing fibroblast-like cells</p> Signup and view all the answers

    Which lineage can mesenchymal stem cells (MSCs) differentiate into?

    <p>Osteogenic lineage</p> Signup and view all the answers

    Which of the following are advantages of dental mesenchymal stem cells?

    <p>Lack of morbidity at the donor site</p> Signup and view all the answers

    What is one of the primary goals of regenerative medicine?

    <p>To replace lost or damaged tissues or organs</p> Signup and view all the answers

    Which type of stem cells are dental pulp stem cells (DPSCs) derived from?

    <p>Neural crest</p> Signup and view all the answers

    What do dental pulp stem cells (DPSCs) differentiate into?

    <p>Smooth muscle cells</p> Signup and view all the answers

    What significant interaction is crucial for the organogenesis of teeth?

    <p>Interaction between dental epithelium and mesenchyme</p> Signup and view all the answers

    Which type of cells do epithelial stem cells (EpSC) primarily differentiate into?

    <p>Ameloblasts</p> Signup and view all the answers

    What is a characteristic of bioengineered teeth?

    <p>Correct responsiveness to mechanical stress</p> Signup and view all the answers

    Which type of stem cells are known for having chondrogenic potentials in vitro?

    <p>Dental pulp stem cells (DPSCs)</p> Signup and view all the answers

    Which stem cells have been reported to differentiate into both neural and vascular endothelial cells?

    <p>Dental Pulp Stem Cells (DPSCs)</p> Signup and view all the answers

    Which stem cells are known to exhibit higher differentiation capabilities than both BMSCs and DPSCs?

    <p>Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs)</p> Signup and view all the answers

    What types of cells can Periodontal Ligament Stem Cells (PDLSCs) differentiate into?

    <p>Bone, cementum, and ligament-like tissues</p> Signup and view all the answers

    From where are Stem Cells from Apical Papilla (SCAPs) isolated?

    <p>Root apex of developing tooth</p> Signup and view all the answers

    What is a unique characteristic of Dental Epithelial Stem Cells?

    <p>Ameloblasts are lost upon tooth eruption</p> Signup and view all the answers

    What indicates the presence of well-developed ameloblasts in tissue after transplantation?

    <p>Positive staining for amelogenin</p> Signup and view all the answers

    What defines odontogenic potential in tissue?

    <p>The capacity to induce gene expression and commence tooth genesis</p> Signup and view all the answers

    Which mesenchyme is capable of odontogenic competence?

    <p>Mesenchyme derived from the cranial neural crest</p> Signup and view all the answers

    What happens when early dental epithelium is recombined with non-neural crest derived mesenchyme?

    <p>Prevention of tooth formation</p> Signup and view all the answers

    Which animals have the ability to continually replace lost teeth?

    <p>Most nonmammalian species</p> Signup and view all the answers

    What is the initial response of living odontoblasts to enamel and dentin loss?

    <p>Synthesis of reparative dentin</p> Signup and view all the answers

    What role do TGFβ growth factors play in large lesions?

    <p>They recruit pulp perivascular stem cells</p> Signup and view all the answers

    What is a potential future approach for tooth repair using adult stem cells?

    <p>Cultivation in biodegradable scaffolds matching tooth shape</p> Signup and view all the answers

    What is the primary goal of the conditions chosen for odontoblast and ameloblast differentiation?

    <p>To correctly replace missing dental materials</p> Signup and view all the answers

    What type of tumor is a central giant cell tumor (CGCT)?

    <p>Benign and locally destructive</p> Signup and view all the answers

    Which of the following treatments is NOT used for central giant cell tumors?

    <p>Chemotherapy</p> Signup and view all the answers

    What surprising development occurred during the 5-year follow-up of the pediatric patient post-reconstruction?

    <p>Development of a left mandibular third molar</p> Signup and view all the answers

    What is the source of tooth-related cells preferred for tooth replacement?

    <p>Isolated stem cells from corresponding teeth tissues</p> Signup and view all the answers

    The process of creating tooth-like structures experimentally involves the recombination of which types of cells?

    <p>Epithelial and mesenchymal cells or intact dental epithelium and mesenchyme</p> Signup and view all the answers

    What is the purpose of culture techniques in the context of tooth replacement?

    <p>To yield large quantities of required cells</p> Signup and view all the answers

    An adequate microenvironment for tooth-like growth should support which of the following?

    <p>3D tooth-like growth and genuine tooth production</p> Signup and view all the answers

    What was observed within 1 day of organ culture after injecting dissociated mesenchymal cells and epithelial cells into a collagen drop?

    <p>Cell-to-cell compaction was observed.</p> Signup and view all the answers

    How long did it take for the transplanted bioengineered tooth germ to erupt and reach the occlusal plane with the lower first molar?

    <p>49 days</p> Signup and view all the answers

    Which structure was confirmed to be maintained in the bioengineered mature tooth after transplantation?

    <p>Periodontal ligament</p> Signup and view all the answers

    What is indicated about the bioengineered teeth components' enamel and dentin hardness?

    <p>They were in the normal range.</p> Signup and view all the answers

    What was achieved by transplanting bioengineered tooth germs into a subrenal capsule for 30 days?

    <p>Development of a mature functional tooth.</p> Signup and view all the answers

    How long did it take for the bioengineered tooth germ implants to successfully erupt after transplantation?

    <p>37 days</p> Signup and view all the answers

    What type of integration was achieved with the bioengineered tooth unit?

    <p>Bone integration</p> Signup and view all the answers

    What successful outcome was reported regarding the eruption of the GFP-labelled bioengineered tooth?

    <p>It erupted in the oral environment of adult mice.</p> Signup and view all the answers

    Study Notes

    Stem Cells & Regenerative Medicine

    • Stem cells can self-renew over time and differentiate into specialized cells like muscle, blood, and brain cells.
    • Stem cells are classified by their plasticity (developmental versatility).
    • Totipotent stem cells can differentiate into all cell types and an entire organism.
    • They are fertilized eggs and cells after few divisions.
    • Pluripotent stem cells can create all tissue types but not an entire organism
    • These cells, arising from the inner cell mass, need the outer layer (placenta) to function fully.
    • Multipotent stem cells are less versatile, differentiating into a limited range of cells within a tissue type
    • Offspring of pluripotent cells become progenitors (e.g., blood, skin, nerve cells).
    • Adult stem cells are multipotent, replacing damaged or lost cells in differentiated tissues.
    • They are undifferentiated cells in differentiated tissues
    • Adult stem cells have been identified in various tissues (blood, neural, endothelial, muscle, mesenchymal, gastrointestinal, and epidermal).
    • Tissue-specific stem cells are harder to isolate and less easily maintained in culture than embryonic stem cells.
    • Induced pluripotent stem cells (iPSCs) are engineered in a lab by reprogramming tissue-specific cells (like skin) into pluripotent cells mirroring embryonic stem cells.
    • Viruses are used in the process, raising cancer risks.
    • iPSCs have been sourced from dermal fibroblasts, skin keratinocytes, amniotic fluid-derived cells, CD34 blood cells, and mesenchymal stem cells.
    • Mesenchymal stem cells (MSCs) are a type of adult stem cell extensively studied, often found in bone marrow, but can also be isolated from fat or cord blood.
    • MSCs can generate osteogenic, chondrogenic, and adipogenic cells.
    • In vitro odontogenesis involves inducing dental epithelial-like cells from mouse ES cells, or iPSCs differentiating into tooth-related structures, including dental mesenchymal cells used in regeneration.
    • Advantages of dental mesenchymal stem cells include high reprogramming efficiency, multipotency, ease of acquisition, and low morbidity at the donor site.
    • Applications of dental stem cells are focused on repairing damaged teeth structures (including dental pulp regeneration, periodontal complex regeneration, osseous regeneration, and other tissue regeneration in medicine).
    • Regenerative medicine aims to recreate fully functioning tissues and organs to replace those lost due to disease, injury, or aging, including hair follicles and mammary glands.

    Regenerative Dentistry

    • In vitro odontogenesis involves three-dimensional bioengineered teeth and tooth germ generation.
    • Bioengineered teeth (in vitro) have correct tooth structure, masticatory function, and nervous response to mechanical stress.
    • Tooth development relies on reciprocal interactions between ectoderm-derived epithelium and neural crest-derived mesenchyme.
    • In the lab, tooth formation requires epithelial cells for initial signals to mesenchyme cells and the presence of both to develop a tooth.
    • Stem cells are a source for lab-induced teeth. These stem cells of focus are epithelial stem cells (ameloblasts) and mesenchymal stem cells (odontoblasts, cementoblasts, osteoblasts and fibroblasts).

    Human Postnatal Mesenchymal Stem Cells

    • Postnatal stem cells include Dental pulp stem cells (DPSCs), cells from exfoliated deciduous teeth (SHEDs), periodontal ligament stem cells (PDLSCs), cells from apical papilla (SCAPS), and dental follicle progenitor cells (DFPCs).
    • These cells have slightly different potencies and some cells are derived from neural crest or mesoderm.

    Dental Pulp Stem Cells (DPSCs)

    • DPSCs are a mesenchymal type of cell found inside dental pulp, differentiating into osteoblasts, smooth muscle cells, adipocyte-like cells, neurons, dentin, and dentin-pulp-like complexes.
    • In vitro experiments have shown chondrogenic potentials.
    • Overall, DPSCs show more suitability than BMSCs for mineralized tissue/bone regeneration.
    • DPSCs can differentiate into neural and vascular endothelial cells.

    Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs)

    • SHEDs are progenitor cells from the deciduous tooth pulp remnants.
    • SHEDs exhibit a higher proliferation rate and differentiation capacity than BMSCs, and even some DPSCs in several studies.
    • SHEDs can differentiate into osteoblasts, odontoblasts, adipocytes, and neural cells.

    Periodontal Ligament Stem Cells (PDLSCs)

    • PDLSCs originate from the neural crest.
    • They exhibit characteristics similar to MSCs and can develop into osteoblasts, cementoblasts, adipocytes, chondrocytes, Periodontal ligament, and cementum-like tissue in vivo.

    Stem Cells from Apical Papilla (SCAPs)

    • SCAPs are cells isolated from the apical root of developing teeth.
    • They exhibit characteristics of MSCs and can differentiate into osteoblasts, adipocytes, chondrocytes, and neurons under the right conditions.

    Dental Follicle Progenitor Cells (DFPCs)

    • DFPCs are stem cells from the dental follicle (surrounding the tooth germ).
    • The follicle contains ectomesenchymal cells that develop into periodontium.
    • DFPCs can differentiate into osteoblasts, adipocytes, chondrocytes, and neural cells.

    Dental Epithelial Stem Cells

    • Ameloblasts are not readily found in postnatal dental tissues, being lost during tooth eruption.
    • Recent studies show that the epithelial cell rest of Malassez (ERM) can differentiate into ameloblast-like cells, expressing cytokeratin and amelogenin proteins in vitro.
    • Enamel-like tissues developed eight weeks after transplantation, indicating the presence of developed ameloblasts.

    Odontogenic Potential and Competence

    • Odontogenic potential refers to a tissue's ability to induce gene expression in an adjacent tissue and initiate tooth development.
    • Initially, odontogenic potential resides in the dental epithelium but later shifts to the mesenchyme (as shown in mice).
    • Odontogenic competence is a tissue's ability to reciprocate odontogenic signals and support tooth/dentin development; only neural crest-derived mesenchyme possess this competence.
    • Combining early epithelial tissue with non-neural crest-derived mesenchyme results in no tooth being formed.
    • Recombination of first branchial arch epithelium and second arch mesenchyme (or certain neural crest tissues) does result in tooth formation.

    Partial Tooth Repair

    • Gradual enamel/dentin loss and pulp exposure prompts living odontoblasts to produce reactionary dentin.
    • Large lesions lead to odontoblast death, releasing TGFβ growth factors.
    • These factors recruit pulp stem cells, which migrate and produce reparative dentin.
    • Enamel proteins (primarily amelogenin) are found in odontoblasts implying synthesis and deposition of enamel.
    • Adult stem cells and their cultivation/multiplication in a biodegradable scaffold can guide odontoblast and ameloblast differentiation.
    • In vitro and in vivo studies have shown promising partial tooth repair results.

    Is Human Tooth Regeneration a Prospective Clinical Reality or a Fantasy?

    • Some animals continually replace teeth throughout life (polyphyodonty).
    • In some animals (mice, voles), damaged teeth can be repaired or replaced with stem cells.

    Bioengineered Tooth Implant Development

    • Developing a bioengineered tooth into the correct structure in an oral cavity.
    • Successfully erupting teeth 37-49 days after transplantation in mice.
    • Reaching the occlusal plane with opposing teeth in mice
    • Bioengineered mature teeth require bone integration after transplantation to maintain periodontal ligament (40 days in studies).
    • Bioengineered tooth enamel and dentin hardness are within normal ranges.

    Replacement Methods for a Whole Tooth

    • Tooth-related cells, preferably stem cells.
    • Odontogenic epithelial cells (of human origin, like ERM, impacted teeth, etc).
    • Using impacted or developing teeth or combining dissociated epithelial/mesenchymal tissues or intact dental epithelium/mesenchyme to generate tooth-like structures.

    Culture Techniques

    • Supporting 3D tooth-like growth leading to tooth-like bud or even replicas.
    • Utilizing artificial, tooth-shaped biodegradable scaffolds.

    Surgical Techniques

    • Ability to implant bioengineered tissue/tooth germ into the prepared empty alveolar socket
    • Resulting in proper root, periodontal ligament, and osteointegration development.
    • Enabling bioengineered teeth growth, morphogenesis, and eruption

    Novel Three-Dimensional Cell Manipulation Methods (for Whole Tooth Regeneration)

    • Methods are illustrated by diagrams and include steps such as 3D cell manipulation, bioengineered germ tooth transplantation, tooth eruption, and bioengineered tooth unit engraftment.

    Engraftment of Bioengineered Tooth

    • Shown via diagrams, highlighting steps in cell manipulation, bioengineered tooth unit (including components like dentin and enamel), and methods of visualization and observation (e.g., microscopy, micro-CT scanning).

    Transplantation of Bioengineered Tooth Germ

    Methods and diagrams illustrating cell preparation, collagen gel formation, extraction, wound healing, and transplantation. Also includes images for observation at various time points post-implantation

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    Description

    Explore the fascinating world of stem cells and their potential in regenerative medicine. This quiz covers the different types of stem cells, their properties, and classifications, including totipotent, pluripotent, and multipotent cells. Test your knowledge on their roles in repairing and regenerating tissues.

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