Documentation of Normal and Leukemic Myelopoietic Progenitor Cells with High-Resolution Phase-Contrast Time-Lapse Cinematography

Abstract

The high-resolution phase-contrast, time-lapse cinematography using oil immersion lenses and 16-mm film demonstrates the kinetic cell events as maturation, locomotion, mitosis, and apoptosis of cells cultivated at 37 °C for up to 10 days. 0.5 v/v frozen-thawed sera with presumably high cytokine concentrations were added to the plasma or agar clot. Vital progenitor cells from human bone marrow and blood have a large, bright, unstructured nucleus with a large nucleolus and a narrow rim of cytoplasm (nuclear/cytoplasmic volume ratio = 0.7). Their nuclei are 6–14 µm in diameter and double their volume within 8 h. Many (70%) move at a mean speed of 2 µm/min, and many (30%) multiply with α-2α mitoses, generating progenitor cell families. Various disturbances during the course of mitosis lead to the formation of polyploid cells, thereby yielding the megakaryocytic cell line. Some of the progenitor cells undergo asymmetric α-αn mitoses: One of the two initially identical daughter cells remains a progenitor cell in the morphological sense, whereas the other daughter cell – depending on the size of its mother cell – matures in the same culture medium to form a granulocytopoietic, monocytopoietic or erythrocytopoietic cell line. – In acute myeloid leukemias (AML), the blasts and their nuclei are slightly larger than the corresponding progenitor cells and move faster (5 µm/min). Symmetric α-2α mitoses permit unlimited multiplication of the leukemic blasts if contact with cytotoxic lymphocytes does not render them apoptotic. This results in more stromal cells than normal. Granulocytopenia, monocytopenia, and anemia occur due to the genetic impairment of signaling control for asymmetric α-αn mitoses, and thrombocytopenia occurs due to the reduction in polyploidization.