Wound Restorative Power of Halimeda macroloba/ Mesenchymal Stem Cells in Immunocompromised Rats via Downregulating Inflammatory/Immune Cross Talk

Impaired skin wound healing is still a major challenge, especially with immunocompromised patients who express delayed healing and are susceptible to infections. Injection of rat-derived bone marrow mesenchymal stem cells (BMMSCs) via the tail vein accelerates cutaneous wound healing via their paracrine activity. The present work aimed to investigate the combined wound-healing potential of BMMSCs and Halimeda macroloba algae extract in immunocompromised rats. High-resolution liquid chromatography-mass spectrometry (HR-LC-MS) investigation of the extract revealed the presence of variant phytochemicals, mostly phenolics, and terpenoids, known for their angiogenic, collagen-stimulating, anti-inflammatory, and antioxidant properties. The BMMSCs were isolated and characterized for CD markers, where they showed a positive expression of CD90 by 98.21% and CD105 by 97.1%. Twelve days after inducing immunocompromise (40 mg/kg hydrocortisone daily), a circular excision was created in the dorsal skin of rats and the treatments were continued for 16 days. The studied groups were sampled on days 4, 8, 12, and 16 after wounding. The gross/histopathological results revealed that the wound closure (99%), thickness, density of new epidermis and dermis, and skin elasticity in the healed wounds were considerably higher in the BMMSCs/Halimeda group than the control group (p < 0.05). RT-PCR gene expression analysis revealed that the BMMSCs/Halimeda extract combination had perfectly attenuated oxidative stress, proinflammatory cytokines, and NF-(K)B activation at day 16 of wounding. The combination holds promise for regenerative medicine, representing a revolutionary step in the wound healing of immunocompromised patients, with still a need for safety assessments and further clinical trials.