Ischemic Brain Stroke and Mesenchymal Stem Cells: An Overview of Molecular Mechanisms and Therapeutic Potential

Table 1

Summary of the most recent studies using animal models of ischemic stroke and mesenchymal stem cell therapy.

Sr#	Types of model	Source of stem cells	Time of administration	Dose	Delivery route	Efficacy	Important findings
1	Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion	Mesenchymal stem cells (MSCs)	3-7 days after MCAO	^6 cells/200 UL PBS	Intravenous administration into the tail vein	Enhanced repair to ischemic stroke, through suppression to ischemia-induced microglial activation	This study observed a decreased expression of mincle, a damage-associated molecular pattern (DAMP) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke [109]
2	Brain stroke model	Rat (r) MSCs	1 hour after the ischemia/reperfusion	10^6 ION labeled MSCs in 10 μL saline	Injected into the right CC 1 h after the ischemia/reperfusion procedure	Crosstalk with the CP enhances MSC proliferation and migration in a transwell assay	These findings could shift cell therapy strategies for stroke from intravenous delivery of MSCs to their direct injection into lateral ventricles harboring the CP, which could enhance functional recovery [110]
3	Establishment of transient middle cerebral artery occlusion model	Human cranial bone-derived mesenchymal stem cells (hcMSCs)	3 or 24 h after MCAO	3 or 24 h after MCAO	The cells were administered intravenously through the tail vein	Suppresses the damage of residual nerve cells and leads to functional recovery	This is the first report demonstrating a functional recovery effect after ischemic stroke following hcMSC transplantation [111]
4	Middle cerebral artery occlusion (MCAO)	Conditioned medium (CM) derived from human embryonic MSC (hESC-MSC)	Either one time (1 h post MCAO) or three times (1, 24, and 48 h post MCAO)	5 μL at a flow rate of 0.5 μL/min	Intracerebroventricular	Improved neurogenesis and angiogenesis to accelerate the recovery of cerebral ischemia insult	hESC-MSC-CM remarkably attenuates neurological deficits as well as lesion volume in MCAO rats [112]
5	Mouse model of transient focal cerebral ischemia	Tropomyosin receptor kinase B (TrkB) gene-transfected mesenchymal stem cells (TrkB-MSCs)	Five days after MCAO	^6/2 μL phosphate-buffered saline (PBS)	Injected at an infusion rate of 0.5 μL/min into the peri-infarct site: anteroposterior	TrkB-MSCs promote the expression of BDNF and NT4, induce the differentiation of TrkB-MSCs, and improve motor function	TrkB-MSCs improve motor function in the mouse model [113]
6	Intraluminal middle cerebral artery occlusion (MCAO)	Neural stem cells were isolated from the subventricular zone of the rat brain.	24 hours after local ischemia	floating cells in 100 μL of PBS	External carotid artery (ECA) lumen	The transplantation of neural stem cells within 24 hours after ischemia led to a reduction in the neural cells death	Reduction in the neural cell death in the ischemic zone and the brain damage decreased significantly [114]
7	Ischemic stroke mice	Neural stem cells (NSCs)	24 h after MCAO operation	cells	i.v. injection	The BDNF-NSC treatment significantly increased the brain BDNF level	The present study investigates the ROS-responsive charge-reversal polymer B-PDEA as the first successful nonviral vector for effective genetic transfection of NSCs [115]