Inter- and intra-site heterogeneity in the expression of fetal-like phenotypic characteristics by gingival fibroblasts: potential significance for wound healing.
We have previously reported that fetal and adult skin fibroblasts display distinctive migratory phenotypes on 3-D collagen substrata and that these behavioural characteristics may be quantified by a function defined as the cell density migration index (CDMI). Subsequent work indicated that this difference in migratory phenotype was due to the production by fetal fibroblasts of a migration stimulating factor (MSF) that is not produced by normal adult skin fibroblasts. We now present data indicating that: (a) unselected fibroblasts obtained from 14/14 (100%) of adult gingival explants expressed fetal-like CDMI values compared to only 1/10 (10%) of similarly explanted paired skin cells; (b) 12/12 (100%) of these gingival fibroblast lines also produced detectable quantities of MSF compared to 0/9 (0%) of the tested skin cells; (c) by microdissection studies, gingival fibroblasts obtained from different anatomical microdomains consisted of behaviourally distinct subpopulations, with cells derived from the papillary tips (PAP fibroblasts) displaying fetal-like CDMI values and persistent MSF production, whilst cells obtained from the deeper reticular tissue (RET fibroblasts) were adult-like with respect to these two criteria; (d) PAP fibroblasts were also smaller and achieved higher saturation cell densities compared to paired RET cells; (e) PAP fibroblasts passaged in vitro underwent a fetal-to-adult phenotypic transition characterized by the adoption of various RET cell characteristics, including the acquisition of CDMI values falling within the adult range and cessation in MSF production; and (f) early passage PAP fibroblasts incubated in the presence of an affinity-purified anti-MSF rabbit polyclonal antibody were induced to alter their migratory phenotype and exhibited CDMI values falling within the adult range. Statistical analysis indicated a highly significant correlation between the expression of a fetal-like CDMI and production of MSF (P < 0.00001, using the Fisher exact contingency test). Taken together, these observations suggest that the production of MSF by PAP fibroblasts is responsible for their characteristically fetal-like migratory behaviour. The existence of such inter- and intra-site phenotypic heterogeneity in populations of skin and gingival fibroblasts is discussed in the context of fibroblast lineage relationships and the possible contribution of persistently fetal-like fibroblast subpopulations to connective tissue function in wound healing.
Irwin
C R
CR
School of Biological Sciences, University of Manchester, UK.
Picardo
M
M
Ellis
I
I
Sloan
P
P
Grey
A
A
McGurk
M
M
Schor
S L
SL
D000328:Adult; D002452:Cell Count; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D016207:Cytokines / Q000096:biosynthesis; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D005353:Fibronectins; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010641:Phenotype; D014945:Wound Healing / Q000502:physiology
D016207:Cytokines; C067625:FN1 protein, human; D005353:Fibronectins