Therapeutic potential of recombinant human type XVII collagen in wound healing and bullous pemphigoid: From bench to bedside

Objective

To investigate the effects of recombinant human type XVII collagen (RHCXVII) on the proliferation and adhesion of primary human keratinocytes (HPKCs) and to observe its clinical efficacy and safety in bullous pemphigoid (BP).

Methods

The RHCXVII was produced by genetic recombination technology and characterized by Fourier transform infrared (FTIR) spectroscopy. HPKCs were obtained from human foreskin and seeded onto culture plates coated with RHCXVII at concentrations of 10, 50 and 100μg/ml. The proliferation and relative adhesion of HPKCs were assessed by Cell Counting Kit-8 (CCK-8) and adhesion assays, respectively. Trajectories and velocities of HPKCs were recorded using a living cell imaging platform. To assess the effects of RHCXVII on HPKCs, E-cadherin, integrinα6 and laminin α3 mRNA levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) assays. The patient test sites were treated with RHCXVII, while the contralateral sides served as controls. This was performed in combination with systemic glucocorticoid treatment. Bilateral wound healing was recorded at various time points and the efficacy in BP was assessed.

Results

RHCXVII exhibited the anticipated structural characteristics of recombinant collagen and was deemed suitable for utilization in the present study. HPKCs demonstrated robust growth in culture plates precoated with RHCXVII, expressing keratin 15 (K15). After 3, 5 and 7 days, RHCXVII at a concentration of 10 µg/ml significantly promoted the proliferation of HPKCs (P<0.05). Furthermore, the optimal relative adhesion of HPKCs was observed when cells were cultured on RHCXVII at a concentration of 100 µg/ml (P<0.01). The mRNA levels of E-cadherin, integrinα6 and lamininα3 in HPKCs cultivated in wells coated with RHCXVII were considerably higher compared to the control group (P<0.05). The study encompassed a total of 12 patients. The mean time to resolution of lesions on the treated sides was 11.08 days, significantly shorter than the 13.42 days observed on the control sides. The mean time to blister resolution was 2.3 days shorter on the treated sides than on the controls. By day 7, the percentage improvement in wound healing compared to the baseline was 7.75 % greater on the treated sides than on the control sides. The study noted a high level of patient satisfaction and no occurrence of significant adverse events.

Conclusion

RHCXVII has the capacity to promote HPKC growth and adherence. In clinical applications, it has been demonstrated to accelerate wound healing in patients with bullous diseases (BD), thereby reducing the risk of subsequent secondary infection. Its potential as an adjunct treatment for wound repair in diseases such as BD merits further investigation.