Strategies to Improve the Efficiency of Transplantation with Mesenchymal Stem Cells for the Treatment of Ischemic Stroke: A Review of Recent Progress

Abstract

Cerebral ischemia is a common global disease that is characterized by a loss of neurological function and a poor prognosis in many patients. However, only a limited number of treatments are available for this condition at present. Given that the efficacies of these treatments tend to be poor, cerebral ischemia can create a significant burden on patients, families, and society. Mesenchymal stem cell (MSC) transplantation treatment has shown significant potential in animal models of ischemic stroke; however, the specific mechanisms underlying this effect have yet to be elucidated. Furthermore, clinical trials have yet to yield promising results. Consequently, there is an urgent need to identify new methods to improve the efficiency of MSC transplantation as an optimal treatment for ischemic stroke. In this review, we provide an overview of recent scientific reports concerning novel strategies that promote MSC transplantation as an effective therapeutic approach, including physical approaches, chemical agents, traditional Chinese medicines and extracts, and genetic modification. Our analyses showed that two key factors need to be considered if we are to improve the efficacy of MSC transplantation treatments: survival ability and homing ability. We also highlight the importance of other significant mechanisms, including the enhanced activation of MSCs to promote neurogenesis and angiogenesis, and the regulation of permeability in the blood-brain barrier. Further in-depth investigations of the specific mechanisms underlying MSC transplantation treatment will help us to identify effective methods that improve the efficiency of MSC transplantation for ischemic stroke. The development of safer and more effective methods will facilitate the application of MSC transplantation as a promising adjuvant therapy for the treatment of poststroke brain damage.

Mesenchymal Stromal Cells in Ischemic Brain Injury

“…Due to the promising safety profile of mesenchymal stromal cells (MSCs) in bloodborne diseases, coupled with the cells' multi-faceted therapeutic mechanisms, such as angiogenic, neurogenic, and vasculogenic, among other regenerative features, MSC transplantation for stroke has been translated from the lab to the clinic [24,25]. MSCs can influence the paracrine system to produce factors that promote microglia activation, increase astrocyte survival, and promote the bystander effect [25][26][27].…”

“…The inflammatory response following a stroke can be reduced by MSC's immunomodulatory effect, a main driving factor in functional recovery and patient outcomes [25]. MSC therapy is a frontrunner in a clinical setting since, as a vial therapy, it can be feasible, readily accessible, and safe for patients, as demonstrated by preceding clinical trials [24,25]. While preclinical models have shown efficacy, this has not carried over into clinical trials, leaving much to be discovered on MSC administration and viability [26].…”

“…Preclinical trials lack understanding in comorbidities associated with stroke, such as obesity and hypertension, which may contribute to the lack of efficacy [23,28]. This disconnect may be decreased with priming effects and standardization for clinical administration and methodology [24,29,30]. Another explanation for this disconnect may stem from differences in translating the results of animal models to human models, such as immunological function and viability.…”

Uwhangchungsimwon Inhibits Oxygen Glucose Deprivation/Re-Oxygenation-Induced Cell Death through Neuronal VEGF and IGF-1 Receptor Signaling and Synaptic Remodeling in Cortical Neurons

“…Other studies showed that VCAM-1 is an angiogenesis-related marker [ 14 ] and that VEGF can activate the signal transduction pathways that regulate VCAM-1 expression [ 15 ]. Additionally, enhanced neovascularization and neurogenesis could be the essential mechanisms by which insulin-like growth factor-1 (IGF-1)/IGF-1R improves functional recovery after stroke [ 16 ].…”