Evaluation of GMP-manufactured pooled human umbilical cord-derived mesenchymal stem cells on lipopolysaccharide-induced lung injury in Sprague-Dawley rats

Abstract

In recent times, mesenchymal stem cells (MSCs) are being widely employed in regenerative medicine. Human umbilical cord-derived MSCs (hUC-MSCs) are a class of multifunctional stem cells that can be used in the treatment of acute or chronic diseases. In the present work, the efficacy of hUC-MSCs was assessed for the mitigation of lipopolysaccharide-induced (LPS) lung injury in rats. Besides efficacy, other parameters such as body weight and temperature, necropsy and gross pathology, broncho-alveolar lavage fluid (BALF), immunogenicity, and histopathology were evaluated. Acute lung injury (ALI) was induced by intratracheal administration of LPS (2.5 mg/kg) which lead to a substantial increase in the content of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, total protein, neutrophils, lymphocytes, and macrophages. Intravenous administration of hUC-MSCs (2 × 106 and 10 × 106 cells/kg body wt.) considerably decreased LPS-induced pulmonic inflammation, as revealed by declines in total protein content of BALF and pro-inflammatory cytokines. In comparison with the LPS group, rats treated with hUC-MSCs demonstrated a considerable improvement in myeloperoxidase activity. The lung histopathology revealed the defensive effect of hUC-MSCs, whereas, rats from the LPS group showed aggravated lung injury. On the whole, the results and observations proved the efficacy of UC-MSCs in the treatment of ALI, and hence hUC-MSCs hold abundant potential for upcoming clinical trials.