TABLE 1.

The challenge and research progress for therapies of stroke.

Therapy	Advantages	Current limitation	Structure transformation	Drug combination
Stem cell	Highly multipotent, differentiate into various types of neural cells such as neurons, oligodendrocytes, and astrocytes; autologous leads to low immunoreactivity	Risk of tumor formation; allogeneic may have immune reject; low infraction targeting; difficult to get large amount; more studies need to be done to confirm dosage, administration methods, and time window	Increase infraction targeting: ferrimagnetic iron oxide nanochains or ECM hydrogel delivery; decrease tumor formation: co-deliver with super-paramagnetic iron oxide nanoparticles or PEGylated super-paramagnetic iron oxide nanoparticles to increase neuron-like differentiation; decrease immune reject: Overexpression of IL-4/IL-10 in MSCs	Extend therapeutic window, inhibit side effects, and enhance therapeutic effects: tPA, minocycline, Niaspan, TCM, TMP, EPO, NBP, Sodium Ferulate, cyclosporin A, propranolol, and chlorzoxazone
Exosomes	The lipophilicity makes it easy to cross BBB; contain various cargos which plays important role for cellular interactions; no immune rejection	Production costs much and takes a long time; hard to distinguish the efficiency for itself and cargos; more studies need to be done to confirm dosage, administration methods, and time window	Selective expression of cargos: overexpress miR-25-3p, miR-21-5p, miR-873a-5p, miR-124, miR-193b-3p, and miR-132-3p; inhibit miR-206 or EP4	Enhance therapeutic effects: rosuvastatin
Traditional Chinese medicine	Wide range of herbal spices and can combine with different types of medicines to have multiple functions; no chemical synthesis is required	Specific mechanism is unsure; the quality of each TCM is different; inner toxicity; high incidence of liver and kidney injury	Analyze the structure of the active ingredient, modify and synthesize it artificially, or semi synthesize compounds such as NBP, PNS, and Sal	Extend therapeutic window, inhibit side effects, and enhance therapeutic effects: tPA with T541, MSCs with TMP, clopidogrel with PNS/Danshen/Ginkgo, Nimodipine with Ginkgo, and resolvin D1 with Xuebijing