Autocrine and paracrine growth stimulation of cells derived from human skin

Abstract

A sensitive serum-free culture system was used to demonstrate that cells derived from normal human skin release soluble mediators which can modulate keratinocyte, melanocyte, and fibroblast growth in vitro. In M199 supplemented with epidermal growth factor, hydrocortisone, insulin, transferrin, triidothyronine, bovine serum albumin, and an extract of bovine hypothalamus, keratinocytes underwent approximately three to five cumulative population doublings (CPD) over a 7-day period. Addition of 20% keratinocyte-conditioned medium more than doubled keratinocyte growth and increased fibroblast growth 25-40% above controls. Dermal fibroblasts maintained in the same serum-free hormone-supplemented medium (SFHSM) alone underwent approximately 4.5-5.5 CPD over a 7-day period; 20% fibroblast-conditioned medium increased fibroblast growth 50-80% and increased keratinocyte growth 30-50%. Melanocytes maintained in the same SFHSM underwent approximately 1 CPD over a 14-day period and 2 CPD if the medium was supplemented with 2% fetal bovine serum (FBS). Addition of 20% melanocyte-conditioned medium more than doubled melanocyte growth in either SFHSM or in medium containing 2% FBS, but decreased both keratinocyte and fibroblast growth up to 30-60%. None of the conditioned media altered cellular morphology. These data provide the first demonstration of mutual growth modulation by cell types normally contiguous in vivo and expand existing evidence for autocrine and paracrine growth regulation by normal human cells.

Insulin Like Growth Factor-1 and -2 and Their Role in the Re-Epithelialisation of Wounds; Interactions with Insulin Like Growth Factor Binding Protein Type 1

“…Several growth factors are important in this process (10,24,36). Clinical and experimental evidence suggests that locally produced factors are vital for the completion of wound healing in vivo: wound fluid from acute wounds stimulates fibroblast and endothelial cell growth (16).…”

Purification and characterization of a newly identified growth factor specific for epithelial cells.

“…It has been postulated that their storage, release, and contact with specific target cells are regulated by this interaction (25,28). While mesenchymal-derived effectors of epithelial cell proliferation have also been described (29)(30)(31) …”

Induction of nerve growth factor receptors on cultured human melanocytes.

“…Thus far, reported growthpromoting activities for human melanocytes in vitro include serum (2,3,28), choleragen and other agents that increase cAMP (2,3,28), phorbol esters (2), and, most recently, basic fibroblast growth factor (41). Growth-stimulating activities for human melanocytes have also been described in various conditioned media and cell or tissue extracts (4,(42)(43)(44), but these factors remain incompletely characterized. Our present observations agree with earlier results (3,28) that NGF is not a mitogen for human melanocytes.…”