Cell-based Therapy for Acute Organ Injury

Abstract

Critically ill patients often suffer from multiple organ failures involving lung, kidney, liver or brain. Genomic, proteomic and metabolomic approaches highlight common injury mechanisms leading to acute organ failure. This underlines the need to focus on therapeutic strategies affecting multiple injury pathways. The use of adult stem cells such as mesenchymal stem or stromal cells (MSC) may represent a promising new therapeutic approach as increasing evidence shows that MSC can exert protective effects following injury through the release of pro-mitotic, anti-apoptotic, anti-inflammatory and immunomodulatory soluble factors. Furthermore, they can mitigate metabolomic and oxidative stress imbalance. In this work, we review the biological capabilities of MSC and the results of clinical trials using MSC as therapy in acute organ injuries. Although preliminary results are encouraging, more studies concerning safety and efficacy of MSC therapy are needed to determine their optimal clinical use.

Postinjury Inflammation and Organ Dysfunction

“…141 Initially, MSC cells were believed to regenerate dysfunctional, damage organs, however, later it became clear that their beneficial effects were mediated by secretion of factors. MSCs tend to migrate toward sites where there is inflammation or injury, thus dysfunctional organs are potential targets.…”

Human Embryonic Stem Cells in the Treatment of Patients with Traumatic Brain Injury

“…Further, Tajiri et al reported that stem cells served a biobridge in injured brain site to initiate the endogenous repair mechanisms [30]. The use of adult MSCs or stromal cells represent a promising new therapeutic approach as these cells have protective effects through the release of promitotic, antiapoptotic, antiinflammatory and immunomodulatory soluble factors [31]. Although physiotherapy plays an important role in TBI, but is unable to cure coma patients and prognostic potential for this therapy is still insufficient.…”

Treating childhood traumatic brain injury with autologous stem cell therapy

“…intracerebral), or intra-arterially [28], and each injection route comes with advantages and disadvantages: intravenous injections are not very invasive but may be unable to surpass the BBB, intra-arterial injections is more invasive but has a higher probability of mobilizing cells across the BBB, while intracerebral injections display the highest degree of cell engraftment but are by far the most invasive. The anti-inflammatory effects seen with peripheral injections are likely due to the systemic dispersion of anti-inflammatory molecules that are not able to penetrate intact BBBs [35, 42–43]. However, such peripheral injections may show a greater degree of success in acute stages when the BBB is injured, allowing the anti-inflammatory molecules to more easily reach the CNS [35].…”

“…However, such peripheral injections may show a greater degree of success in acute stages when the BBB is injured, allowing the anti-inflammatory molecules to more easily reach the CNS [35]. Furthermore, peripheral injections are most efficiently used early after the injury, as they pose less of a threat of damaging recently injured brain regions [35, 42]. With chronic inflammation, injecting stem cells directly into the brain may be most effective when dealing with chronic TBI, as the brain has had some period to heal while at the same time likely presenting with tapered chemoattractants to induce migration of stem cells from periphey [45–46].…”