Hematopoiesis and Stem Cells

Hematopoiesis

• Normally, 75% of bone marrow cells belong to the myeloid series, which produces white blood cells, while 25% are maturing red cells
• Despite this, there are over 500 times more red cells in the circulation than white cells

Stem Cells

• Hematopoietic stem cells (HSCs) have extensive proliferative capacity and the ability to:
  • Give rise to new stem cells (self-renewal)
  • Differentiate into any blood cell lines (pluripotency)
• HSCs differentiate into committed stem cells (progenitor cells), which in turn form various types of blood cells

Clonal Hemopoiesis

• Pluripotent stem cells multiply and commit to specific cell lines, forming progenitor cells
• Progenitor cells regulate the proliferation and maturation of specific blood cells

Progenitor Cells

• Committed stem cells lose their capacity for self-renewal and become irreversibly committed to specific cell lines
• Progenitor cells are regulated by hormones or substances, allowing them to:
  • Proliferate
  • Undergo maturation

Erythropoiesis

• Erythropoiesis is the process of red blood cell formation
• Stages of RBC development:
  • Pluripotential hematopoietic stem cell
  • Committed stem cell
  • Proerythroblast
  • Early, intermediate, and late normoblasts
  • Reticulocytes
  • Erythrocytes

Stages of RBC Maturation

• Pronormoblast:
  • 15-20µm in size
  • Basophilic cytoplasm
  • Nucleus with nucleoli
  • No hemoglobin
• Basophilic normoblast:
  • Large nucleus
  • Basophilic cytoplasm
  • Active mitosis
  • Slightly reduced in size
• Polychromatophilic normoblast:
  • Chromatin lumps
  • Hb starts appearing
  • Reduced mitoses
• Orthochromatic normoblast:
  • Small and pyknotic nucleus
  • Eosinophilic cytoplasm
  • Mitoses absent
• Reticulocyte:
  • Reticular nuclear fragments
  • Nucleus extruded
  • Slightly larger than RBCs

Erythrocytes Production

• Process of erythropoiesis takes 5 days from pronormoblast to reticulocyte phase
• Maturation phase from reticulocyte to RBC takes 2 days
• Features of RBC maturation:
  • Reduction in size
  • Disappearance of the nucleus
  • Acquisition of hemoglobin

Control of Erythropoiesis

• Erythropoiesis is stimulated by erythropoietin hormone
• Stimulated by:
  • Hypoxia (low oxygen)
  • Anemia
  • Hemorrhage
  • High altitude
  • Lung disease
  • Heart failure

Erythropoietin

• Glycoprotein hormone produced mainly by the kidneys (90%) and liver (10%)
• Stimulates erythropoiesis by acting on committed stem cells to induce proliferation and differentiation of erythrocytes in bone marrow
• Site of action: bone marrow

Factors Affecting Erythropoiesis

• Hormonal factors:
  • Androgens
  • Thyroid hormones
  • Glucocorticoids
  • Pituitary gland
  • Haematopoietic growth factors
• Nutritional requirements:
  • Amino acids
  • Iron
  • Vitamin B12 and Folic acid
  • Vitamin C
  • Proteins

Clinical Aspects

• Anemias: reduced RBC count or reduced Hb concentration
• Polycythemia: increased RBC count
• Erythrocytosis: increased RBC count due to hypoxia