Tissue Engineering and Cancer Biology Quiz

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Questions and Answers

What is a characteristic of injectable stem cells?

  • They are more invasive than other methods.
  • They allow for controlled growth factor release. (correct)
  • They can only grow in one shape.
  • They require a surgical implant.

Which of the following materials is not classified as a polymer used in tissue engineering?

  • Matrigel
  • Collagen
  • Hydroxyapatite (correct)
  • Fibrin

What does solid scaffold manufacturing utilize for accuracy?

  • Drawing templates.
  • Manual sketching techniques.
  • 3D printing with standard materials.
  • Computer-aided design. (correct)

What innovative approach have researchers used to address the regeneration of human tissues and organs?

<p>Growing heart tissue on spinach leaves. (A)</p> Signup and view all the answers

Which of the following is a common material used in the creation of decellularized matrices?

<p>Fibrin (C)</p> Signup and view all the answers

What characterizes cancer at a cellular level?

<p>Unregulated cell growth and spread to other sites (B)</p> Signup and view all the answers

Which type of cancer originates from epithelial cells?

<p>Adenocarcinoma (C)</p> Signup and view all the answers

What role do mutagens play in the development of cancer?

<p>They cause alterations to the DNA sequence. (C)</p> Signup and view all the answers

What type of mutations primarily lead to cancer development?

<p>Somatic mutations (D)</p> Signup and view all the answers

Which of the following is NOT classified as a carcinogen?

<p>Physical exercise (D)</p> Signup and view all the answers

Which type of cancer is specifically associated with mesoderm cells?

<p>Sarcomas (C)</p> Signup and view all the answers

What is a major difference between cancer and other genetic diseases?

<p>Cancer mutations are primarily somatic. (D)</p> Signup and view all the answers

Which characteristic differentiates skin cancer from lung cancer?

<p>Specific genetic mutations (C)</p> Signup and view all the answers

What is a significant disadvantage of using retroviruses in gene therapy?

<p>They cannot infect non-dividing cells. (D)</p> Signup and view all the answers

Which characteristic makes adenoviruses advantageous for gene therapy?

<p>They are efficient at transferring genes. (B)</p> Signup and view all the answers

Which of the following is true about liposomes in gene therapy?

<p>They can carry large DNA molecules. (B)</p> Signup and view all the answers

What is the method used to identify cancer stem cells (CSCs) mentioned in the content?

<p>Spheroid colony formation (D)</p> Signup and view all the answers

What is a disadvantage of using adenoviruses for gene therapy?

<p>They can trigger an immune response. (C)</p> Signup and view all the answers

Which vector is exclusively used in ex vivo therapy?

<p>Retroviruses (D)</p> Signup and view all the answers

Which surface marker is specifically known as prominin-1?

<p>CD133 (A)</p> Signup and view all the answers

What is a common disadvantage associated with liposomes in gene therapy?

<p>They have inefficient gene transfer. (A)</p> Signup and view all the answers

What is one of the roles of CD44 as described in the content?

<p>Binding to the extracellular matrix (A)</p> Signup and view all the answers

How do retroviruses achieve stable modification of target cells?

<p>By integrating their genome into the host chromosome. (B)</p> Signup and view all the answers

Which intracellular marker is NOT mentioned as a marker for cancer stem cells?

<p>p53 (D)</p> Signup and view all the answers

What is a significant limitation of using cellular markers for isolating cancer stem cells?

<p>The number of isolated cells is limited (B)</p> Signup and view all the answers

Which gene therapy vector does not facilitate uncontrolled integration and has non-integration to the chromosome as an advantage?

<p>Adenoviruses (C)</p> Signup and view all the answers

Which of the following is a role of EpCAM as stated in the content?

<p>Supporting cell migration (D)</p> Signup and view all the answers

Which of the following is NOT a characteristic of immature cells in culture?

<p>Die in cell culture (A)</p> Signup and view all the answers

Which protein is associated with oncogenic potential as mentioned in the content?

<p>EpCAM (A)</p> Signup and view all the answers

What effect did the therapy have on the immune system?

<p>The therapy partially restored the immune system. (D)</p> Signup and view all the answers

What is a significant consequence of ammonia accumulation in the blood for individuals with Ornithine transcarbamylase deficiency?

<p>Toxicity that particularly affects the nervous system. (A)</p> Signup and view all the answers

Why were all gene therapy trials using retroviral vectors in blood stem cells halted by the FDA in 2003?

<p>Patients developed leukemia-like conditions. (D)</p> Signup and view all the answers

For what condition was the stem cell gene therapy Strimvelis designed?

<p>Adenosine deaminase deficiency. (D)</p> Signup and view all the answers

Which therapeutic gene-targeting strategy can be utilized against HIV?

<p>Targeting CCR5 and CD4. (B)</p> Signup and view all the answers

What aspect of gene therapy in blood cells was demonstrated by the prior study treating bubble baby syndrome?

<p>It highlighted risks such as developing leukemia. (B)</p> Signup and view all the answers

Which of the following best describes the nature of the enzyme production in the mentioned gene therapy?

<p>The enzyme production was temporarily stimulated. (B)</p> Signup and view all the answers

Which of the following diseases can be potentially treated using similar therapeutic strategies as mentioned?

<p>HIV. (B)</p> Signup and view all the answers

What is the primary objective of tissue engineering?

<p>To assemble constructs that restore or improve damaged tissues (A)</p> Signup and view all the answers

Which type of artificial tissue has been approved by the FDA for limited use in human patients?

<p>Engineered skin and cartilage (C)</p> Signup and view all the answers

What challenge has hindered the expansion of cells in tissue engineering?

<p>Inability to expand cells in vitro (C)</p> Signup and view all the answers

Which of the following is a component of tissue engineering?

<p>Vascular networks (B)</p> Signup and view all the answers

What materials have been used to create artificial skin in successful medical applications?

<p>Cowhide, shark cartilage, and plastic (D)</p> Signup and view all the answers

What is a major factor that has limited clinical advancements in regenerative medicine?

<p>Inadequate vascularity of engineered tissues (A)</p> Signup and view all the answers

For how long has tissue engineering been a field of research?

<p>Over 70 years (A)</p> Signup and view all the answers

Why was it difficult to expand most human cells in vitro during the early 1990s?

<p>Technological limitations in culture techniques (D)</p> Signup and view all the answers

Flashcards

Injectable stem cells

A method of delivering stem cells into the body by injecting them directly into the desired area. This technique is less invasive than other methods and allows the cells to adapt to their surrounding environment.

Decellularized matrix

A scaffold created from the naturally occurring extracellular matrix (ECM) of an organ. This material is biocompatible and provides a framework for new tissue growth.

Biomaterial

A biological material that serves as a template or framework for tissue regeneration. These are derived from natural sources like collagen or ECM.

Solid scaffold manufacturing

A method of manufacturing solid scaffolds for tissue engineering using computer-aided design (CAD). This technique allows for precise customization of the scaffold to match the shape of the defect.

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Decellularization

A process of removing cells from a donor organ while preserving the organ's structure and ECM. This creates a scaffold that can be seeded with new cells for tissue regeneration.

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Tissue Engineering

The practice of combining scaffolds, cells, and biologically active molecules into functional tissues.

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Goal of Tissue Engineering

A field aiming to restore, maintain, or improve damaged tissues or organs using engineered constructs.

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Regenerative Medicine

A field that encompasses tissue engineering, cell therapy, and regenerative medicine.

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Inability to Expand Cells In Vitro

A crucial challenge in regenerative medicine is to be able to grow cells outside the body in a lab.

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In Vitro

The process of growing or expanding cells in a laboratory setting outside of their natural environment, often in a culture dish.

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Inadequate Vascularity

The lack of adequate blood vessels to deliver nutrients and remove waste products, hindering tissue growth.

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Scaffolds

Materials used as a foundation for tissue growth, providing structure and support for cells.

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Biologically Active Molecules

Biologically active molecules, like proteins or growth factors, that guide cell behavior and promote tissue formation.

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What is cancer?

A group of diseases characterized by uncontrolled cell growth, invasion, and spread to other parts of the body.

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What are carcinomas?

A type of cancer that originates in epithelial cells, which line surfaces and cavities of the body, making up 85% of cancers.

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What are sarcomas?

A type of cancer that originates from mesodermal cells, responsible for development of bones, muscles, and other tissues.

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What are adenocarcinomas?

A type of cancer that originates in glandular tissues, which secrete substances like hormones.

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What are carcinogens?

Agents that can cause cancer by damaging DNA and promoting uncontrolled cell growth.

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What are mutagens?

Agents that cause changes in the sequence of DNA, often leading to mutations that contribute to cancer.

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Cancer is a disease of the genome at the cellular level.

Cancer develops due to changes in the genetic makeup of cells, mainly through somatic mutations (changes in non-reproductive cells).

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What are the genetic alterations in cancer?

The genetic alterations that underlie cancer can range from subtle point mutations (single base changes) to large chromosomal rearrangements (deletions, translocations).

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Retroviruses

A type of gene therapy vector that is a virus that has been modified to be incapable of replicating independently. It is used only in ex vivo therapy.

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Adenoviruses

A type of viral vector commonly used in gene therapy. Can be produced in high concentrations in cultures.

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Liposomes

A common gene delivery system that is a spherical structure made of lipids. An aqueous solution is surrounded by a lipid shell.

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Viral vectors and cancer risk

A disadvantage of viral vectors used in gene therapy is the possibility of causing cancer.

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Retroviruses and stable modification

An advantage of using ex vivo therapy with retroviruses is that they can permanently change target cells.

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Adenovirus and transient gene expression

A disadvantage of adenoviruses is that the effect of the transferred gene is temporary.

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Liposome inefficiency

A disadvantage of using liposomes in gene therapy is that they are not very efficient at delivering their cargo.

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Liposome and transient gene expression

A disadvantage of liposomes is that the effect of the transferred gene is temporary.

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In vivo gene therapy

A type of gene therapy where the therapeutic gene is delivered directly into the bloodstream, often targeting the liver.

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Ornithine transcarbamylase deficiency (OTCD)

A genetic disorder causing ammonia buildup in the blood, especially affecting the nervous system. This condition can be treated using in vivo gene therapy targeting the liver.

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Gene therapy in blood cells

A gene therapy strategy using retroviral vectors to deliver therapeutic genes into hematopoietic stem cells, which then give rise to all blood cells.

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X-linked severe combined immunodeficiency disease (SCID)

A severe immune deficiency disorder often referred to as 'bubble baby syndrome', historically treated with gene therapy using retroviral vectors.

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Therapeutic gene for various diseases

Gene therapy targeting hematopoietic stem cells can be used for a variety of diseases, including those affecting the immune system, like HIV.

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Targets for HIV gene therapy

Certain proteins on the surface of cells, like CD4 and coreceptors (CCR5 or CXCR4), can be targeted by gene therapy to treat HIV infection.

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Strimvelis

A specific gene therapy using stem cells to treat ADA-SCID. This therapy was approved in 2016.

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Gene therapy

The use of gene therapy to modify or replace faulty genes in order to treat inherited disorders or other diseases. This field has shown promise but also encountered safety challenges.

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Spheroid Colony Formation

A method to isolate cancer stem cells (CSCs) by growing them in a special serum-free medium that encourages them to form non-adherent clusters (spheroids).

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CD133

A cell surface marker, also known as prominin-1, that is commonly used to identify and isolate CSCs. It is expressed in embryonic and hematopoietic stem cells.

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CD44

A cell surface marker often used to isolate CSCs. It's a transmembrane glycoprotein that plays a critical role in cell adhesion, migration, and differentiation.

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EpCAM

A transmembrane glycoprotein involved in cell adhesion and signaling, potentially linked to cancer development.

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Aldehyde Dehydrogenase 1 (ALDH1)

An intracellular marker that helps identify CSCs. This enzyme is involved in detoxification and is often elevated in CSCs.

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Oct3/4

A marker found within CSCs that plays a key role in the self-renewal of these cells, similar to its role in embryonic stem cells.

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Nanog

An intracellular marker associated with CSCs, crucial for maintaining stem-cell properties and preventing differentiation.

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Isolation of CSCs with Markers

The use of cell surface markers to isolate CSC populations from tumors. However, it has drawbacks like a limited number of cells that can be isolated, which can be a challenge with small tumors.

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Study Notes

Stem Cells in Gene Therapy/Gene Editing

  • Cell/gene therapy is a branch of Regenerative Medicine focused on replacing, engineering, or regenerating human cells, tissues, or organs to restore normal function.
  • Gene therapy delivers therapeutic genes into a patient's cells to treat disease.
  • Cell therapy delivers intact, living cells into a patient to treat disease.
  • Combination cell/gene therapy approaches aim to insert genes into a patient's own cells to control diseases, and are now in clinical trials.

Gene Therapy

  • Gene therapy is an experimental technique using genes to treat or prevent diseases.
  • Future approaches may involve inserting genes into patient cells instead of drugs or surgery.
  • Several gene therapy approaches are being researched, including:
    • Replacing mutated disease-causing genes with healthy copies.
    • Inactivating, or "knocking out," mutated genes that function improperly.
    • Introducing a new gene to fight a disease.
  • Although promising, gene therapy is still risky and under study for safety and effectiveness.
  • Current gene therapy trials are focused on diseases with no other known cures.

Different Routes of Gene Therapy

  • Ex vivo approach:
    • Target cells are removed from the body and grown in a lab (in vitro).
    • Genes are introduced into the cultured cells.
    • The modified cells are returned to the patient.
    • Examples: fibroblasts, hematopoietic cells, stem cells
  • In vivo approach (Direct Gene Transfer):
    • Genes are introduced directly into affected tissue of the body without removing cells.
    • Special delivery vehicles are typically required for gene transfer
    • Examples: lungs, brain

Ex Vivo and In Vivo Gene Therapies

  • Ex vivo gene therapy is often used with blood cells (lymphocytes or hematopoietic stem cells) for conditions affecting the hematopoietic system.
  • In vivo gene therapy is used in cancer treatment using oncolytic adenoviruses, and in muscular dystrophy or hemophilia treatment with adeno-associated vectors. In other instances, non-viral vectors are used since they are not oncogenic.

Ex Vivo Gene Therapy: Putting Functional Genes Into Marrow Stem Cells

  • This approach involves removing stem cells from the patients bone marrow or blood, modifying them in a lab, and then reintroducing them to the patient.

Methods of Gene Delivery

  • Physical methods:
    • Parenteral injection
    • Microinjection
    • Aerosol
    • Gene gun
  • Chemical methods:
    • Calcium phosphate
    • DEAE-Dextran
    • Liposomes
  • Biological methods:
    • Viral vectors (retrovirus, adenovirus, HSV)

Common Vectors Used For Gene Therapy

  • Retroviruses:
    • Used in ex vivo therapy only.
    • Advantages: chromosomal integration and stable modification of target cells.
    • Disadvantages: uncontrolled integration, potential oncogenicity, and inability to infect non-dividing cells.
  • Adenoviruses:
    • Second most common delivery system, which can be produced in large quantities in cultures.
    • Advantages: infect non-dividing cells, non-integration.
    • Disadvantages: transient expression due to episomal integration and may provoke an immune response.
  • Liposomes:
    • Lipid bilayers surrounding an aqueous vesicle that can carry large DNA.
    • Advantages: safer than viral vectors, can carry large DNA molecules.
    • Disadvantages: inefficient and transient gene transfer.

Somatic Cell Therapy

  • Gene insertion into somatic cells (fibroblasts, myoblasts, epithelial cells, etc.)
  • Corrects the genetic defect in the patient; However the change is not inheritable.

Germ Line Therapy

  • Introducing the foreign gene into germ cells (sperm, ovum, fertilized egg)
  • Modifies features in both somatic and germ cells (heritable changes).
  • Considered unethical and not advocated in current use.

History of Gene Therapy

  • Early clinical trials started in the 1980s and a patient died in a 1990s trial.
  • The first report of a human gene therapy trial involving stem cells started in the 1990s involving treatment of a rare inherited genetic disease.
  • In 2003, FDA halted trials using retroviral vectors in blood stem cells.

Some Targets for Gene Therapy

  • Gene therapy can be used to treat/prevent diseases such as cancer or genetic disorders. Infections are also being targeted.

Gene Therapy in Blood Cells (Hematopoietic Stem Cells)

  • Blood stem cells are a target for gene therapies that can treat various conditions of the hematopoietic system, and often using ex vivo approaches.

Somatic Cell Therapy History

  • The first human gene transfer using stem cells was performed in 1990.

Stem Cells and Tissue Engineering

  • Tissue engineering is a field that combines scaffolds, cells, and biologically active molecules to create functional tissues.
  • The goal is to restore, maintain, or improve damaged tissues and organs.
  • Examples include artificial skin and cartilage, but clinical applications are frequently limited.

Regenerative Medicine

  • Regenerative medicine focuses on enabling the body to heal itself through tissue engineering, and cell therapy and regeneration.

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