Wound Healing 3 - Tissue Repair and Regeneration

Study Notes

The ability of tissues to repair themselves is influenced by their intrinsic proliferative capacity
Mechanisms regulating cell populations can be altered by:
- Increased or decreased rates of stem cell input
- Cell death (apoptosis)
- Changes in proliferation or differentiation rates

Labile Tissues: High proliferation capacity for successful regeneration as long as the stem cell pool is maintained, e.g., skin, oral cavity, fallopian tubes, haematopoietic cells
Stable Tissues: Minimal replicative activity in their normal state, with limited regeneration capacity but can proliferate in response to injury or loss of tissue mass, e.g., liver, kidney, pancreas
Permanent Tissues: Insufficient proliferative capacity to regenerate; repair typically involves scar formation, e.g., brain, heart

Two varieties: embryonic and tissue stem cells
Present in many labile and stable populations
Located in discrete compartments (e.g. basal layer of epidermis, hair follicle)
The ability of a tissue to regenerate depends on the integrity of the stem cell population
A separate stem cell pool exists in bone marrow (haemopoietic stem cells)

Tissues are composed of continuously dividing cells (e.g., epithelia, haemopoietic tissues), quiescent cells capable of proliferation (e.g., most parenchymal organs), and non-dividing cells (e.g., neurons, skeletal/cardiac muscle)
Cell proliferation is regulated by the cell cycle, stimulated by growth factors, and interactions with extracellular matrix
The liver can regenerate through cytokines and growth factors in response to inflammation and loss of liver mass – regeneration can happen by surviving hepatocytes or from progenitor cells

In epithelia (e.g., intestinal tract, skin), injured cells can be replaced by cells & differentiation of tissue stem cells
Some organs (e.g., pancreas, adrenal gland, thyroid, and lungs) have limited regenerative abilities
Kidney repair involves hypertrophy and hyperplasia of proximal duct cells in response to surgical removal
Tissue architecture must remain intact for effective regeneration. Damage from infection/inflammation can result in scarring
Liver abscesses can cause extensive destruction, leading to scar formation despite remaining cells' regenerative ability

If regeneration is insufficient, injured cells are replaced by connective tissue, forming a scar
Scarring occurs with severe or long-lasting tissue damage, including harm to parenchymal, epithelial, and connective tissue
Scar formation is distinct from tissue regeneration (restoring tissue components)
Scar refers to the replacement of parenchymal cells by collagen, common after myocardial infarction

Clot formation, inflammation, angiogenesis, and formation of granulation tissue
Fibroblasts migrate, proliferate, and produce collagen; connective tissue remodeling
Laying down of fibrous tissues
Macrophages eliminate offending agents and stimulate cell proliferation; TGF-β is a contributor to fibrosis
Maintaining a balance of factors (fibrogenic agents, extracellular matrix (ECM) and tissue inhibitors of MMPs (TIMPs)) to manage ECM remodeling

The combination of proliferating fibroblasts, loose connective tissue, and new blood vessels forms granulation tissue
It is unique to wound healing
Its gross appearance is pink, soft, and granular (e.g., beneath a skin wound scab)
Resident and mesenchymal-derived fibroblasts become pro-fibrotic, laying down ECM proteins, and differentiating into myofibroblasts for contraction

Tissue repair can be impaired by various reducing quality/adequacy of reparative process
Extrinsic factors (e.g., infection), intrinsic factors (e.g., to injured tissue), or systemic/local factors