In vitro characterisation of human cleft fibroblasts isolated from patients with differing cleft manifestations

Saeed, Naveed (2019). In vitro characterisation of human cleft fibroblasts isolated from patients with differing cleft manifestations. University of Birmingham. Ph.D.

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Abstract

Following surgical correction of cleft lip and palate a number of patients develop post-operative complications including oronasal-fistulae (ONF) and hypertrophic scarring (HTS). As these conditions can form due to pathological wound healing, this study aimed to characterise fibroblast behaviour, derived from patients with differing cleft phenotypes, to identify potential contributing factors. Fibroblasts were isolated from oral mucosal tissues derived from 29 cleft patients and were subsequently characterised and compared in terms proliferation, migration, ECM deposition and gene expression. Cleft fibroblasts were clustered into two statistically distinct migratory groups: fast and slow, with fast migrating fibroblasts secreting greater amounts of collagen. Although these groups did not correlate with cleft phenotype, CL fibroblasts all presented increased motility coupled with increased collagen deposition and upregulation of COL1A1. As both elevated motility and collagen secretion are hallmarks of HTS, it is possible that patients with faster migrating fibroblasts, including those derived from CL, may be at greater risk of pathological wound healing. Further, as fast migrating fibroblasts contained greater quantities of F-actin and upregulated ARP2, a major component of the ARP2/3 complex which acts as an actin filament nucleator, the observed increase in motility may be a result of altered cytoskeletal dynamics.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):