Proliferative capacity of cell cultures derived from the human placenta

Abstract

The placenta consists largely of fetal tissue, yet at term it displays histological signs of deterioration not apparent in the fetus. To determine whether the apparent degeneration of the placenta is genetically determined, the life-spans of placental cell cultures and the proportion of placental cells capable of incorporating [3H]thymidine for replicative DNA synthesis in vitro were measured. Under the culture conditions employed, the placental cells were removed from the influence of many extrinsic factors thought to play a role in the degeneration of the placenta in vivo. Cultures of fibroblast-like cells derived from the placenta exhibited a reduced life-span and correspondingly reduced proportion of cells able to incorporate [3H]thymidine for DNA synthesis in comparison to cultures derived from the fetal skin and the maternal decidua. These results suggest that intrinsic cellular processes may be involved in the apparent degeneration of the placenta.

Biochemical Studies on Acid Phosphatase in Human Placenta and Fetal Liver during Development

“…SN is the 105.000 g supernatant. of the hydrolase in term placenta possibly accounts for the decreased phys iological function and degeneration or aging of the tissue [15]. The activity of ACP in P, and P2 fractions of the placenta decreases progressively with advancement of pregnancy.…”

Comparative Studies on Acid Phosphatase Isozymes of Developing Human Placenta and Fetal Liver

“…The progressive increase in the activity of each isozyme with increase in gestation shows a positive correlation of these isozymes with the growth and developmental processes of these two rapidly growing tissues. The diminished activity of each ACP isozyme in term placenta possibly accounts for the de creased physiological function and degeneration or ageing of the tissue (17).…”

The Concept of Telomeric Non-Reciprocal Recombination (TENOR) Applied to Human Fibroblasts Grown in Serial Cultures: Concordance with Genealogical Data

“…Such waves can account for the nicks and plateaux in culture growth patterns found in several studies. 96,109-111,113,178 3 H-thymidine proliferation assays exhibited proliferation spikes at mid-life passages, 6,9 which might indicate fast-growing rejuvenated cell branches initiated by a wave of replicatively senescent cells. Measurements of cloning efficiencies also indicated a proliferation spike at mid-life passages.…”

“…Mounting evidence shows that replicatively senescent fibroblasts are already present in early culture passages. Proliferation assays such as direct microscopic observation, 2 cinematography, 3 3 H-thymidine incorporation, [4][5][6][7][8][9] BrdUrd-labeling tests, 10,11 detection of cell cycle stage-specific antigens, 12,13 and counting cells expressing replicative senescence-associated ␤-galactosidase 14,15 have all revealed that, even in earlypassage cultures, not all of the cells are able to divide. As a rule, these replicatively senescent cells are large, partially flat and spread out, and dividing cells are small, thick, and elongated spindle-shaped.…”

“…2,3,7,9,26,38,44,45 As shown for a great number of different fibroblast strains, there is a progressive increase in replicatively senescent cells until the culture cannot be propagated further. 2,[4][5][6][7][8][9][10][11][12][13][14][15]46,47 It has been repeatedly demonstrated that the onset of that terminal state is clearly related to the replicative age, that is, to mitotic time, of the culture and not to chronological time, [48][49][50][51] and that cell proliferation capacities are not adversely affected by growth at low cell density [52][53][54] nor by enzymatic treatment at passaging. 55 Therefore, the consumption of an intrinsically determined proliferation capacity by divisions represents the final replicative boundary which human fibroblasts cannot continuously bypass.…”