Combined transplantation of human umbilical cord mesenchymal stem cells and MEEK micrografts in rabbits: A long-term self-controlled study.

Abstract

To investigate the efficacy of human umbilical cord mesenchymal stem cells (UCMSCs) in wound healing and scar formation following high-expansion (1:6) MEEK micrografting in rabbits. Four dorsal full-thickness wounds per rabbit (n = 13) received randomized treatments: (A) topical hyaluronic acid (HA) gel + 1 × 10⁷ UCMSCs; (B) topical HA gel only; (C) subfascial normal saline (NS) injection + 1 × 10⁷ UCMSCs; (D) subfascial NS only. Assessments included epithelialization rate, complete epithelialization time (CET), and histological/immunohistochemical analysis (H&E, Masson richrome, Sirius Red, α-SMA, Ki67, CD31) at 0, 1, and 2 months post-healing. UCMSC groups (A, C) showed significantly accelerated healing vs controls (B, D): higher epithelialization rates at post-operative day (POD) 10 (A: 62.0 ± 5.8 % vs B: 56.8 ± 6.2 %, P = 0.014; C: 68.0 ± 10.8 % vs D: 59.2 ± 9.0 %, P = 0.033). Reduced CET (A: 24.5 ± 8.8 d vs B: 29.0 ± 7.9 d, P = 0.013; C:27.2 ± 8.0 d vs D: 31.5 ± 10.9 d, P = 0.032). Histology demonstrated UCMSCs promoted near-normal regeneration (increased skin appendages, improved epidermal/dermal organization, reduced inflammation) and inhibited fibrosis (lower collagen volume fraction and type I/III ratio, P < 0.05). Immunohistochemistry confirmed reduced myofibroblast activation (α-SMA, P < 0.05), microvascular density (CD31⁺, P < 0.05 at POD 70/94), and proliferative cells (Ki67⁺, P < 0.05 at POD 70/94). Topical or subfascial UCMSC therapy significantly accelerates epithelialization and inhibits scar hyperplasia post-MEEK micrografting through regenerative promotion, collagen normalization, and suppression of myofibroblasts/proliferation/angiogenesis, offering a promising strategy for extensive burns.