Tissue Repair and Regeneration Overview

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Questions and Answers

Which cells are primarily involved in the initial inflammatory response to a wound?

  • Fibroblasts and lymphocytes
  • Neutrophils and B-cells
  • Eosinophils and platelets
  • Polymorphs and macrophages (correct)

What is the role of exudate in the wound healing process?

  • To provide a dry environment for cell migration
  • To form scar tissue exclusively
  • To facilitate the diffusion of healing factors and support cell proliferation (correct)
  • To increase the risk of infection

During which stage of wound healing is angiogenesis significantly involved?

  • Inflammatory phase
  • Hemostasis phase
  • Maturation phase
  • Proliferation phase (correct)

How does fibronectin contribute to the wound healing process?

<p>By stabilizing the wound through cross-linking with fibrin (A)</p> Signup and view all the answers

What defines regeneration in the context of tissue repair?

<p>Restoration of original tissue architecture and function (D)</p> Signup and view all the answers

Which type of tissue cells primarily mediate matrix deposition during the healing process?

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

What is the primary function of macrophages in the early stages of wound healing?

<p>To remove damaged tissues and facilitate repair (D)</p> Signup and view all the answers

What occurs immediately after hemorrhage in the tissue healing process?

<p>A fibrin clot forms to stabilize the wound (A)</p> Signup and view all the answers

What is the primary goal of the regeneration process in terms of tissue restoration?

<p>To maintain or re-establish both form and function of the tissue (D)</p> Signup and view all the answers

In the context of regeneration, what role do instructive signals play?

<p>They regulate the cell cycle for a finite number of divisions (A)</p> Signup and view all the answers

Which type of cells is primarily responsible for the inflammatory response during tissue injury?

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

How does the regenerative capacity differ between lower vertebrates and mammals?

<p>Lower vertebrates restore tissue through immune system programming (A)</p> Signup and view all the answers

What is the significance of fibroblasts in the wound healing process?

<p>They help in the deposition of the extracellular matrix (A)</p> Signup and view all the answers

What potential risk is associated with the regenerative process?

<p>Development of cancer-related cellular abnormalities (D)</p> Signup and view all the answers

What is a key factor in the effectiveness of the regenerative response in adult mammals?

<p>The age of the organism (A)</p> Signup and view all the answers

What does morphostasis refer to in the context of regeneration?

<p>The maintenance of both structure and function post-injury (C)</p> Signup and view all the answers

Which statement accurately describes the initial response to tissue damage?

<p>Neutrophil influx and activation of macrophages occur. (A)</p> Signup and view all the answers

What is the primary role of fibroblasts during the regeneration phase?

<p>To remodel the extracellular matrix and support tissue architecture. (A)</p> Signup and view all the answers

Which cell type is primarily responsible for the acute inflammatory response following tissue injury?

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

What is a characteristic of aberrant tissue repair?

<p>Prolonged activation of inflammatory cells leading to excessive scarring. (B)</p> Signup and view all the answers

During tissue regeneration, which process is primarily responsible for reducing chronic inflammation?

<p>Recruitment of T regulatory cells (Treg). (A)</p> Signup and view all the answers

In contrast to neonates, adult mammals primarily exhibit what type of cardiac response to injury?

<p>An acute inflammatory response leading to chronic remodeling. (C)</p> Signup and view all the answers

What defines the process of matrix deposition during tissue repair?

<p>Recruitment of resident macrophages and fibroblasts to synthesize extracellular matrix components. (A)</p> Signup and view all the answers

Which sequence correctly depicts the phases involved in wound healing and tissue repair?

<p>Inflammatory response, regeneration, scarring. (C)</p> Signup and view all the answers

Flashcards

Regeneration definition

Regeneration is the restoration of lost or damaged cells, tissues, and organs to their original structure and function.

Regeneration process requirements

Successful regeneration needs recognition of missing parts, proper integration between newly formed and existing tissues, regulated cell division, and signals that indicate the process is complete.

Regeneration and Cancer

Regeneration has a potential link to cancer-related cellular abnormalities.

Vertebrate cardiac regeneration

The ability of a vertebrate's heart to regenerate varies among species. Lower vertebrates naturally regenerate cardiac tissue; mammals do so less effectively, often dependent on their age and developmental stage.

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Adult mammal regeneration

Adult mammal regeneration of tissues is influenced by age.

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Morphostasis in Regeneration

Regeneration aims to maintain or restore both the structure (form) and function of an injured tissue.

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Cellular Guidance & Termination in Regeneration

Cells involved in regeneration must be correctly guided to the needed areas. Specific cues stop the repair process once it's finished.

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Regeneration versus Repair

Regeneration is more complete, restoring original form and function. Repair is a less comprehensive response, fixing damage but not necessarily returning it precisely to the initial state.

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Regenerative response in neonates

A response in newborn mice (before 7 days old) with effective cardiac tissue repair, similar to fish and amphibians.

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Adult mammalian heart response to injury

An acute inflammatory response leading to chronic, irreversible heart remodeling after a myocardial infarction.

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Regeneration vs. Repair

Regeneration restores the original tissue, while repair replaces it with scar tissue.

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Healthy tissue (monocytes/neutrophils)

Contains little monocyte activity or neutrophil movement, an intact basement membrane.

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Damaged tissue (monocytes/neutrophils)

Has loss of surface layers, influx of neutrophils, activated macrophages and inflammatory monocytes, and release of inflammation factors and pericytes.

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Tissue Regeneration (cells)

Involves epithelial growth, macrophage activation for healing, and matrix changes.

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Aberrant tissue repair

Excessive scarring due to sustained inflammation and impaired epithelial regeneration.

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Treg cells in tissue regeneration

Cells recruited to reduce chronic inflammation during regeneration.

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What are the stages of wound healing?

Wound healing occurs in a defined sequence: 1. Inflammation: removes damaged tissue. 2. Proliferation: new cells and blood vessels form. 3. Remodeling: scar tissue is formed.

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What does exudate do in wound healing?

Exudate supports healing by providing a moist environment, facilitating diffusion of healing factors, promoting cell growth, providing nutrients, and aiding in the removal of dead tissue.

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What is the initial phase of wound healing?

The initial phase begins with bleeding, followed by the formation of a fibrin clot and the recruitment of macrophages to clean up damaged tissue.

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What is regeneration?

Regeneration is the restoration of lost or damaged tissue to its original structure and function.

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What is repair?

Repair is the process of fixing damaged tissue, but it may not fully restore the original structure or function.

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Why is the liver special in regeneration?

The liver has a remarkable ability to regenerate, even after significant damage. It can restore its original size and function.

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What are some examples of skin damage?

Skin damage can include sunburns, burns, itchy wounds caused by bacteria or chronic autoimmune diseases, and cancer.

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How does angiogenesis contribute to wound healing?

Angiogenesis is the formation of new blood vessels during wound healing. It helps supply nutrients and oxygen to the healing area.

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Study Notes

Tissue Repair and Regeneration (MEDC0064-TRAR)

  • This course covers human skin wound healing, tissue repair and principles of regeneration.
  • The course is led by Prof Krista Rombouts, PhD from UCL Institute for Liver and Digestive Health, Regenerative Medicine & Fibrosis Group, Royal Free Hospital, London, UK.

Learning Objectives

  • Understand injury, cellular, and vascular responses.
  • Sequence in wound healing
  • Definitions of Regeneration and Repair
  • Liver and regeneration

Examples of Skin Damage

  • Sunburn/UV
  • Burning wounds
  • Itchy wounds (bacterial/nutritional)
  • Psoriasis (chronic autoimmune disease)
  • Benign skin cancers
  • Malignant skin cancers

Steps in Repair by Scar Tissue Formation

  • Inflammatory response: removal of damaged/dead tissue via polymorphs and macrophages.
  • Proliferation: migration and proliferation of parenchymal and connective tissue.
  • Formation of new blood vessels (angiogenesis) and granulation tissue. (this occurs over a timeframe of hours, days, weeks and months)

A Temporal Journey for Normal Wound Healing

  • Includes various stages such as coagulation, inflammation, proliferation, and maturation/remodeling.
  • Each stage has a specific timeframe (minutes, hours, days, weeks, months, years) with various cellular and biological processes involved.

Wound Healing Exhibits a Defined Sequence

  • Starts with hemorrhage into tissues resulting in formation of a fibrin clot.
  • Macrophages recruit to process cell remnants and damaged ECM
  • Fibronectin, cell debris, and bacterial products attract other cells.
  • The extra-cellular matrix (ECM) is deposited at the wound site.
  • Temporary matrix is removed and replaced by one rich in collagen.

Characteristics of Skin Wounds

  • Cell migration relies on chemical signals and the extracellular matrix.
  • Leukocytes migrate rapidly by forming focal adhesions.
  • Polymorphonuclear leukocytes are rapidly recruited within the first day.
  • Macrophages arrive after neutrophils and persist for days, phagocytosing debris and releasing cytokines/chemoattractants.

Cells in Skin Wounds

  • Fibroblasts, myofibroblasts, pericytes, smooth muscle cells: responsible for fibroplasia, matrix production, wound contraction, strength; recruited by day 3/4
  • Endothelial cells: form capillaries for nutrient/gas exchange, delivery of inflammatory cells; visible beyond day 3.
  • Epithelial cells: migrate across wound surface, through provisional matrix, using stromal collagen
  • Stem cells: provide epidermal/dermal cells; regenerate skin structures (hair follicles, glands; found in bone marrow, hair follicles, basal epidermal layer)

Pro-inflammatory and Anti-inflammatory Cells

  • Neutrophils & mast cells: first responders, important for innate immune response for wound detection, executing rapid response and restoring tissue homeostasis
  • Mast cells: early participant in innate immune system, releasing effector molecules (chemoattractants) to recruit eosinophils/monocytes
  • Macrophages: pivotal for fighting pathogens and tissue healing
  • M1 macrophages: pro-inflammatory phenotype.
  • M2 macrophages: wound-healing phenotype; activated after acute phase of tissue injury
  • Regulatory T (Treg) cells: key player in adaptive immune response after tissue injury; contributing to tolerance.

Chemokines in Wound Healing

  • Early: promotion of inflammation (neutrophils, macrophages) and increase neovessel formation
  • Late: promote scar formation, regression of neovessels, and the termination of the inflammatory response.

Normal vs. Aberrant Regeneration (Examples: Liver Regeneration)

  • Normal early response: rapid cell proliferation, restoration of liver size/function
  • Aberrant regeneration: slow, less efficient cell restoration (e.g., in chronic liver diseases like fatty liver), potential for scar development and organ function loss
  • Liver regeneration: involves distinct phases (priming, proliferation, termination), relies on cell-cell communication (signals like TGF-beta, IL-6), regulated by the precise coordination of various cell types including hepatocytes and non-parenchymal cells.

Regenerative Capacity Across Species

  • Different species exhibit varying capacities for tissue regeneration.
  • Examples in lower vertebrates vs mammals demonstrate the species-dependent regenerative abilities.

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MSc/MRes Human Tissue Repair PDF

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