outline the role of stem cells in cell replacement and tissue repair by mitosis

Replication and Division of Nuclei and Cells

Learning objective

Outline the role of stem cells in cell replacement and tissue repair by mitosis, and understand how this fits into the wider context of chromosome structure, the cell cycle and the consequences of uncontrolled division (Cambridge 9700 syllabus outcomes 5.1‑5.4).

1. Chromosome structure (syllabus 5.1)

• DNA – long double‑helical polymer that carries the genetic code.
• Histones – basic proteins around which DNA winds to form nucleosomes.
• Nucleosome – DNA wrapped around an octamer of histones; the basic unit of chromatin.
• Chromatin – complex of DNA, histones and non‑histone proteins; exists as loosely packed euchromatin (transcriptionally active) or tightly packed heterochromatin (inactive).
• Sister chromatids – two identical copies of a replicated chromosome joined at the centromere.
• Centromere – specialised DNA‑protein region where the kinetochore forms and spindle fibres attach.
• Kinetochore – protein complex on the centromere that links each chromatid to spindle microtubules and is monitored by the spindle‑assembly checkpoint.
• Telomeres – repetitive DNA sequences at chromosome ends that protect coding DNA during replication; they shorten with each division.
• Telomerase – ribonucleoprotein enzyme that adds telomeric repeats, highly active in many stem cells to maintain telomere length.

2. The cell cycle (syllabus 5.2)

Eukaryotic cells pass through a repeating series of phases that ensure accurate DNA duplication and equal chromosome segregation.

Key cell‑cycle checkpoints

• G₁/S checkpoint – tests for sufficient size, nutrients and DNA damage before DNA synthesis.
• G₂/M checkpoint – ensures DNA replication is complete and any damage is repaired before mitosis.
• Spindle‑assembly checkpoint – monitors attachment of all kinetochores to spindle fibres; prevents anaphase onset until correct bipolar attachment is achieved.

2.1 Stages of mitosis (syllabus 5.3)

1. Prophase – chromatin condenses into visible chromosomes; nucleolus disappears; centrosomes migrate and begin forming the mitotic spindle.
2. Metaphase – chromosomes align on the metaphase plate; each kinetochore is attached to spindle fibres from opposite poles.
3. Anaphase – sister chromatids separate at the centromere and are pulled toward opposite poles by shortening spindle fibres.
4. Telophase – nuclear envelopes re‑form around each chromosome set; chromosomes de‑condense; nucleoli re‑appear.
5. Cytokinesis – contractile ring (animal cells) or cell plate (plant cells) divides the cytoplasm, completing cell division.

3. Stem cells in cell replacement and tissue repair (syllabus 5.4)

3.1 Types of stem cells (relevant to the A‑Level syllabus)

3.2 How stem cells replace lost cells (mitotic mechanism)

• Stem cells enter the normal cell‑cycle (G₁ → S → G₂ → M).
• During S‑phase the entire genome, including telomeres, is duplicated; telomerase activity in many stem cells prevents telomere shortening.
• Mitosis (prophase → metaphase → anaphase → telophase) ensures each daughter nucleus receives an exact copy of the parental chromosome set.
• During cytokinesis the two daughter cells diverge:
  • Self‑renewal – one daughter retains stem‑cell characteristics and re‑enters the niche.
  • Differentiation – the other becomes a progenitor that will undergo further divisions and specialise to replace the lost or damaged cells.

3.3 Examples of stem‑cell‑driven repair

• Skin (epidermis) – basal keratinocyte stem cells divide by mitosis; progeny migrate upwards to replace shed keratinocytes.
• Intestinal epithelium – crypt stem cells produce all specialised villus cells; the entire epithelium is renewed every 4–5 days.
• Blood – haematopoietic stem cells in bone marrow give rise to erythrocytes, leukocytes and platelets through successive mitotic divisions.
• Plant meristems – apical meristem cells continuously divide, supplying new cells for shoot and root growth and for repair of injured tissue.

3.4 Regulation of stem‑cell mitosis

• Growth‑factor signals (e.g., epidermal growth factor, fibroblast growth factor) stimulate entry into G₁.
• Cell‑cycle checkpoints (G₁/S, G₂/M, spindle‑assembly) verify DNA integrity, telomere length and correct spindle attachment before progression.
• Stem‑cell niche – the local micro‑environment (extracellular matrix, neighbouring cells, soluble factors) balances quiescence and activation, ensuring appropriate rates of self‑renewal and differentiation.

3.5 Uncontrolled division – tumours

• Failure of checkpoint control or loss of telomerase regulation can allow stem cells (or their progeny) to divide without restraint.
• Resulting chromosomal instability and accumulation of mutations underlie the formation of benign and malignant tumours.
• Many cancers contain “cancer stem cells” that retain self‑renewal capacity; targeting these cells is a major therapeutic strategy.

4. Clinical relevance (concise)

• Regenerative medicine – transplantation of cultured adult stem cells (e.g., bone‑marrow grafts, skin grafts) to replace damaged tissue.
• Gene therapy – stem cells can be edited ex vivo (CRISPR, viral vectors) and re‑introduced, providing a genetically corrected source of replacement cells.
• Cancer research – understanding stem‑cell mitosis and checkpoint failures informs the development of drugs that specifically target cancer stem cells.

5. Summary

Stem cells are specialised undifferentiated cells capable of self‑renewal and of giving rise to differentiated progeny. Their contribution to tissue replacement relies on the standard eukaryotic cell cycle: DNA is duplicated in S‑phase (with telomerase maintaining telomere length), chromosomes are accurately segregated during the four mitotic stages, and cytokinesis creates two daughter cells—one that remains a stem cell and one that differentiates to repair tissue. Tight regulation by growth‑factor signals, the G₁/S and G₂/M checkpoints, and the spindle‑assembly checkpoint, together with the supportive niche, prevents uncontrolled proliferation. Loss of this control leads to tumour formation, linking normal stem‑cell biology directly to cancer. Mastery of these concepts satisfies the Cambridge 9700 outcomes and provides a foundation for future biomedical applications.

6. Suggested diagram (for revision)