Cellular adaptation, tissue regeneration 2024.PDF
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Cellular adaptation and tissue regeneration âš« Overview of adaptation & regeneration âš« Cellular adaptations âš« Healing responses after injury âš« Role of stem cells Learning outcomes âš« âš« âš« To explain the main forms of cellular adaptations to external stimuli To describe the healing responses afte...
Cellular adaptation and tissue regeneration ⚫ Overview of adaptation & regeneration ⚫ Cellular adaptations ⚫ Healing responses after injury ⚫ Role of stem cells Learning outcomes ⚫ ⚫ ⚫ To explain the main forms of cellular adaptations to external stimuli To describe the healing responses after injury To understand the role of stem cells in healing process Cellular adaptation and tissue regeneration ⚫ Overview of adaptation & regeneration ⚫ Cellular adaptations ⚫ Healing responses after injury ⚫ Role of stem cells Repair Regeneration Cellular adaptation and tissue regeneration ⚫ Overview of adaptation & regeneration ⚫ Cellular adaptations ⚫ Healing responses after injury ⚫ Role of stem cells Cellular adaptation ⚫ Cells respond to increased demand and external stimulation by hyperplasia or hypertrophy ⚫ Cells respond to reduced supply of nutrients and growth factors by atrophy ⚫ In some situations, cells change from one type to another, a process called metaplasia ⚫ There are numerous molecular mechanisms for cellular adaptations Hyperplasia Increase in the number of cells in an organ or tissue resulting in increased volume of the organ or tissue ⚫ Can be physiological or pathological ⚫ The process remains controlled ⚫ May lead to cancerous proliferation Mechanisms of hyperplasia ↑Local production of growth factors ↑ Expression of growth factor receptors of the responding cells Activation of particular intracellular signalling pathways Production of transcription factors that turn on many cellular genes Cell proliferation Hypertrophy ⚫ An increase in the size of cells due to synthesis of more structural components, resulting in an increase in the size of the organ ⚫ Can be physiological or pathological ⚫ Caused by increased functional demand or by specific hormonal stimulation Cardiac hypertrophy Normal cardiac myocyte Adaptation response to increased work load Hypertrophic cardiac myocytes Mechanisms of hypertrophy ⚫ ⚫ ⚫ Hypertrophy is the result of increased production of cellular proteins Induced by co-ordinated actions of mechanical sensors, growth factors and vaso-active agents Two main biochemical pathways ⚫ ⚫ IGF1 → PI3K → Akt pathway (physiological) Ang II, ET-1, NA → GPCR → Gαq/11 →MAPK, PKC,PKA (pathological) Hyperplasia and hypertrophy Hyperplasia Hypertrophy Combined hypertrophy & hyperplasia Cell number ↑ Cell size ↑ Cell size + cell number ↑ Hyperplasia and hypertrophy may co-exist Atrophy ⚫ Atrophy is the shrinkage (reduced size) of an organ or tissue from a decrease in cell size and number ⚫ It represents a form of adaptive response and may culminate in cell death ⚫ Physiological atrophy is common during normal foetal development ⚫ Pathological atrophy depends on the underlying cause and can be local or generalized Causes of Atrophy ⚫ Decreased workload (atrophy of disuse): restriction to bed rest leads to skeletal muscle atrophy ⚫ Loss of innervation (denervation atrophy): Nerve damage leads to muscle atrophy Causes of Atrophy ⚫ Diminished blood supply: arterial occlusive disease ⚫ Lack of nutrition ⚫ Loss of endocrine stimulation ⚫ Pressure atrophy (Tissue compressed) Cellular adaptation and tissue regeneration ⚫ Overview of adaptation & regeneration ⚫ Cellular adaptations ⚫ Healing responses after injury ⚫ Role of stem cells Healing responses after injury ⚫ Repair most often consists of a combination of regeneration and scar formation and fibrosis by the deposition of collagen ⚫ The relative contribution of regeneration and scarring in tissue repair depends on ⚫ The ability of the tissue to regenerate ⚫ The extent of the injury Healing responses after injury ⚫ In adult tissues the size of cell populations is determined by ⚫ ⚫ ⚫ The rate of cell proliferation, differentiation The rate of death by apoptosis Differentiated cells incapable of replication are referred to as terminally differentiated cells Healing responses after injury Cellular adaptation and tissue regeneration ⚫ Overview of adaptation & regeneration ⚫ Cellular adaptations ⚫ Healing responses after injury ⚫ Role of stem cells Stem cells ⚫ Stem cells are characterised by ⚫ ⚫ ⚫ ⚫ Their self-renewal properties Their capacity to generate differentiated cell lineages In early stages of embryonic development, stem cells (embryonic stem (ES) cells), are pluripotent they can generate all tissues of the body Pluripotent stem cells → multipotent or unipotent stem cells (more restricted developmental potential), → differentiated cells from the three embryonic layers Stem cell generation and differentiation The zygote, formed by the union of sperm and egg, divides to form blastocysts. The inner cell mass of the blastocyst generates the embryo. The cells of the inner cell mass - embryonic stem (ES) cells, can differentiate into cells of multiple lineages. Stem cells ⚫ Embryonic stem cells The inner cell mass of blastocysts in early embryonic development contains pluripotent stem cells known as ES cells. ⚫ Adult (somatic) stem cells Stem cells present in adult tissues that continuously divide such as the bone marrow, the skin, and the lining of the GI tract ⚫ Induced pluripotent stem cells (iPSC) Differentiated cells of adult tissues can be reprogrammed to become pluripotent (transferring their nucleus to an enucleated oocyte; introducing the key genes). Impact of stem cell research on Biology and Medicine ⚫ To study the specific signals and differentiation steps required for the development of many tissues ⚫ To produce knockout mice, an essential tool to study the biology of particular genes and to develop models of human disease ⚫ To regenerate damaged organs In lecture question and discussion Photomicrographs (a) and (b) show skeletal muscle in transverse section at the same magnification. Both are normal but (b) shows a common adaptive process. Q1: What is the adaptive process? Q2: What is the likely cause of this adaptive change? Q3: Fill the missing words in the sentences. ________is an increase in the size of existing cells accompanied by an increase in their functional capacity. ________is an increase in the number of cells in a tissue caused by increased cell division.
