Intrathecal Injection of Mesenchymal Stromal Cell Cultured on 3D Fiber Ameliorates Multiple Organ Damage in Murine Lupus

Abstract

Up to 60% of patients with systemic lupus erythematosus (SLE) experience autonomic symptom. Sympathetic nervous system damage can cause dysfunction of the bone marrow that activates inflammatory cells, potentially causing multiple organ damage. We hypothesized that sympathetic nervous system damage would induce bone marrow dysfunction with multiple organ damage in SLE, and that multiple organ damage could be improved by therapy targeting the nervous system. Here, we showed that damage to autonomic nerves and Schwann cells occurred in the bone marrow and central nervous system of SLE model mice. A neurotoxic drug increased mortality and induced severe neuropathy and multiple organ damage, while a neuroprotective drug prevented multiple organ damage. The administration of bone marrow-derived mesenchymal stromal cells (BMSCs) cultured on a 3-dimensional fiber scaffold improved bone marrow neuropathy, skin lesions, kidney function, and mortality. Our results reveal that bone marrow neuropathy influence multiple organ damage associated with SLE, and improvement of bone marrow neuropathy by intrathecal injection of BMSC may be a target for SLE multiple-organ damage.

Transcutaneous auricular vagal nerve stimulation alleviated the development of peripheral and central symptoms of systemic lupus erythematosus in MRL/lpr mice

“…2I). Previous studies demonstrated that the expression of TH in LC was signi cantly lower in MRL/lpr mice [30]. To determine whether the taVNS relieved this impairment, we observed the expression of TH in the two groups of mice, found the number of TH + cells were signi cantly higher in the mice that received taVNS (Fig.…”

“…Noradrenaline has an important role in many psychiatric and neurodegenerative disorders and most of the noradrenaline released in the brain is supplied by LC [55,56]. Besides, LC neurons loss is an early feature of depression and neurodegenerative diseases [57,58], which may also exist in MRL/lpr mice [30]. In current study, we found taVNS protected TH + neurons in LC, indicating that the therapeutic effects of taVNS may be related to its activation of LC noradrenergic cells.…”