Intravenous Administration of Adipose-Derived Stem Cell Protein Extracts Improves Neurological Deficits in a Rat Model of Stroke

Abstract

Treatment of adipose-derived stem cell (ADSC) substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E) may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO). We demonstrated that intravenous (IV) injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.

Epigallocatechin-3-gallate preconditioned Adipose-derived Stem Cells confer Neuroprotection in aging rat brain

“…At the same time, the ADSCs not only helped repair the brain tissue, but also triggered the neighboring neurons to do so. Similar findings have been reported where stem cellsecreted factors were shown to have a rejuvenating effect on tissues [12].…”

“…Thus, such holistic approach to therapy would be beneficial for patients with stroke, who are generally at an advanced age and weakened state at stroke onset. Furthermore, damaged neural tissues evidently respond positively to the ADSC extract, even in tissues where donor cells are not found, confirming that secreted factors likely confer the therapeutic effects, which may help integrate both host and donor cells to repair brain damage more robustly [12]. Epigallocatechin-3-gallate (EGCG) is an antioxidant and bioactive polyphenol found in green tea (Camellia sinensis), which is consumed around the world.…”

Transplantation of neural stem cells in the mouse model of ischemic brain stroke and expression of genes involved in programmed cell death

“…Our study suggests that the part of the answer can be found in the tissue treated by transplanted stem cells. The presence of transplanted stem cells supports regenerative events ( 13 , 14 , 17 ). For example, stroke increases the levels of Ripk1 , a necroptosis promotor, while transplanted medium and NSC oppose this process ( Figure 2A ).…”

Efficacy of adipose derived stem cells on functional and neurological improvement following ischemic stroke: a systematic review and meta-analysis

“…Four hundred eighty-six non-duplicated records were found. After screening and assessment of potentially relevant studies, 20 articles were entered into the metaanalysis [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] (Fig. 1).…”