Human adipose-derived mesenchymal stem cells for acute and sub-acute TBI

Abstract

In the U.S., approximately 1.7 million people suffer traumatic brain injury each year, with many enduring long-term consequences and significant medical and rehabilitation costs. The primary injury causes physical damage to neurons, glia, fiber tracts and microvasculature, which is then followed by secondary injury, consisting of pathophysiological mechanisms including an immune response, inflammation, edema, excitotoxicity, oxidative damage, and cell death. Most attempts at intervention focus on protection, repair or regeneration, with regenerative medicine becoming an intensively studied area over the past decade. The use of stem cells has been studied in many disease and injury models, using stem cells from a variety of sources and applications. In this study, human adipose-derived mesenchymal stromal cells (MSCs) were administered at early (3 days) and delayed (14 days) time points after controlled cortical impact (CCI) injury in rats. Animals were routinely assessed for neurological and vestibulomotor deficits, and at 32 days post-injury, brain tissue was processed by flow cytometry and immunohistochemistry to analyze neuroinflammation. Treatment with HB-adMSC at either 3d or 14d after injury resulted in significant improvements in neurocognitive outcome and a change in neuroinflammation one month after injury.

Mesenchymal stem cell immunomodulation: In pursuit of controlling COVID-19 related cytokine storm

“…99,100 approved for clinical use in patients with traumatic brain injury. 101 Another case report described the recovery of a COVID-19 patient with severe inflammation symptoms after treated with allogenic human umbilical cord MSCs (hUCMSCs). 102 A dose of 5 × 10 7…”

“…The study purpose is to evaluate the safety and efficacy of four intravenous infusions of either placebo or HB‐adMSCs in subjects with COVID‐19. HB‐adMSC have been previously approved for clinical use in patients with traumatic brain injury 101 …”

Recent Advances in Stem Cell Therapies to Address Neuroinflammation, Stem Cell Survival, and the Need for Rehabilitative Therapies to Treat Traumatic Brain Injuries

“…However, there is still little known concerning the effects of early verses delayed treatments using MSCs. Using human adipose-derived mesenchymal stem cells (HB-adMSCs), Ruppert et al (2020) explored the neuromodulatory potential of early and delayed administration as a treatment for TBIs [ 5 ]. The delayed treatment design of Ruppert’s study is meant to resemble the time it would take to isolate, expand, characterize, and deliver cells in the absence of previously banked cells.…”

“…Destroyed and damaged cells within the injury area release damage-associated molecular pattern molecules (DAMPS) that stimulate the release of pro- and anti-inflammatory cytokines and reactive oxygen and nitrogen species. The DAMPS are recognized by microglia, astrocytes, neurons and the infiltrating peripheral immune cells which respond by creating the neuroinflammatory response [ 5 , 6 ]. Both the peripheral and neuroimmune responses create a feedback loop that further releases pro- and anti-inflammatory molecular mediators, metalloproteinases, and oxidative metabolites that cause additional damage and perpetuates the neurodegenerative state following the TBI.…”

“…Both the peripheral and neuroimmune responses create a feedback loop that further releases pro- and anti-inflammatory molecular mediators, metalloproteinases, and oxidative metabolites that cause additional damage and perpetuates the neurodegenerative state following the TBI. Together, these immune responses can prolong and exacerbate the pathological response to the injury furthering the risk of developing NDDs [ 5 , 7 ].…”