Keloid patients have higher peripheral blood endothelial progenitor cell counts and CD34⁺ cells with normal vasculogenic and angiogenic function that overexpress vascular endothelial growth factor and interleukin‐8

Abstract

Background One suggested reason for aberrant wound healing in keloid scars is chronic inflammation of the dermis. We hypothesized that excessive blood vessel formation and high capillary density in keloid tissue is caused by dysfunction of endothelial progenitor cells. Methods We compared the number of circulating endothelial progenitor cells and vasculogenic and angiogenic capacity, as well as secretory function, of circulating CD34+ cells in keloid patients and healthy individuals. Results Compared to mononuclear cell cultures from healthy donors, cultures of peripheral blood mononuclear cells obtained from keloid patients showed a more than twofold increase in the number of peripheral blood EPCs (fibronectin‐adhering cells that phagocytized acetylated low‐density lipoprotein and bound Ulex europaeus agglutinin‐I lectin). However, there was no difference in colony‐forming ability and participation in in vitro angiogenesis between circulating CD34+ cells isolated from keloid patients and healthy individuals. This means that circulating CD34+/endothelial progenitor cells in keloid patients have normal vasculogenic and angiogenic function. However, CD34+ cells derived from keloid patients demonstrated a more than sevenfold expression of the interleukin‐8 gene and a more than fivefold expression of the vascular endothelial growth factor gene than CD34+ cells derived from healthy individuals. Conclusions These results support the role of vascular endothelial growth factor and interleukin‐8 in increased recruitment of endothelial progenitor cells in keloid patients.

The Roles of Inflammation in Keloid and Hypertrophic Scars

“…A plethora of factors including IL-6, IL-8, IL-18, chemokine like factor-1 (CKLF-1), prostaglandin produced by cyclooxygenase (COX-1) that exhibit pro-inflammatory roles upon tissue damage have been found significantly elevated in keloid tissue (31,32). Even in the peripheral blood of keloid patients, IL-8 level was 7 fold higher than that of normal people (33). However, it is unclear that the rise of these soluble molecules is cause or consequence of keloid formation.…”

Systemic factors that shape cutaneous pathological scarring

“…These findings suggest that the high circulating EPC numbers in keloid patients may contribute to the immature nature of keloid capillaries. 16 Endostatin is the monomeric C-terminal proteolytic fragment of collagen XVIII. It is a very potent endogenous inhibitor of angiogenesis.…”

A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis

“…The treatment samples of our study revealed increased levels of growth factors such as FDF7, FGF10, TGF-beta, and VEGF. In particular, VEGF showed a profibrotic effect by multiple mechanisms (Tanaka et al, 2019 ). The use of talc enhanced the fibroproliferative pathway typical of hypertrophic scarring resulting in scars that directly activated inflammatory and fibrotic mediators fundamental to the human hypertrophic scarring process which is devoid of epidermal injury.…”