Stem cell therapy in ischemic stroke

Abstract

Objective: Cell-based therapies are being investigated as an adjunct to IV thrombolysis or mechanical thrombectomy in ischemic stroke. This review summarizes the potential applications as well as challenges of intravascular cell delivery in ischemic stroke. Method:We conducted a search of Medline as well as the clinicaltrials.gov Web site for all ongoing human clinical studies using stem cells in ischemic stroke patients. Result:The pros and cons of the various donor cell types and routes of cell delivery, including intravascular delivery, in ischemic stroke are discussed. In addition, the potential challenges in translation from bench to bedside, the optimal techniques for intravascular cell delivery, and an updated comprehensive list of ongoing clinical trials in ischemic stroke are highlighted. Conclusions:Stem cells have shown a promising role in ischemic stroke, in preclinical studies as well as initial pilot studies. Further studies are needed to assess intravascular cell therapy as a potential adjunct to thrombolysis or mechanical thrombectomy in ischemic stroke. Neurology Cell therapy is emerging as a promising new modality for enhancing neurologic recovery in ischemic stroke.1 Numerous basic science studies have demonstrated positive results in animal models of ischemic stroke following implantation of progenitor cells derived from various sources, including adipose, human fetal/embryonic tissue, bone marrow, peripheral, and umbilical cord blood (figure).2 These animal studies have utilized various methods of cell delivery or implantation (table 1), including direct intracerebral (IC) injection, intracisternal/cerebroventricular (ICV), or intravascular routes of delivery such as IV or intra-arterial (IA) infusion.Methods of cellular delivery and implantation. Intracerebral. Direct injection is invasive, and despite being a precise method of cellular delivery and implantation, it results in a poor distribution of cells in the target lesion.3 Initial pilot human studies investigating stereotactic IC cell implantation in patients with chronic stroke also reported adverse events, including seizures, syncope, asymptomatic subdural hematoma, transient motor worsening, and enhancing lesions on MRI. 4,5Intracisternal/cerebroventricular. The ICV route of cell delivery is less invasive than direct IC implantation but is also associated with variable cell migration to the ischemic site.6,7 In a pilot human study investigating ICV delivery in 10 chronic stroke patients (7 ischemic and 3 hemorrhagic), some patients developed fever and meningeal signs 48 hours after cellular delivery via ICV route. IV.Infusion is the least invasive method, allowing wide distribution of cells with exposure to chemotactic signals that potentially guide them toward the target ischemic lesion. This method, however, results in cells being trapped by peripheral organs, including the lungs, liver, and spleen, thereby limiting potential engraftment in the ischemic lesion in the brain.2 Since patients with ischemic stroke commonly ha...

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…One example is the concern regarding IC injections of MSCs to treat myocardial infarction [26] . Similar concerns have been raised in studies that used MSCs to treat stroke [27,28] . A true local injection of MSCs might require a surgical intervention, such as that used in the repair of bone defects.…”

CXCR4+CD45− BMMNC subpopulation is superior to unfractionated BMMNCs for protection after ischemic stroke in mice

“…Cell transplantation-based regenerative therapy provides us with a promising approach for stroke treatment (Bliss et al, 2010; Burns and Steinberg, 2011; Liu et al, 2013; Misra et al, 2012). Compared with other cell sources, bone marrow mononuclear cells (BMMNCs) have attracted the interest of many researchers because their use avoids ethical concerns, and they are easy to obtain and purify.…”

Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Stem Cells in Subacute Ischemic Stroke Patients

“…The authors attributed this “significant neuroprotective effect” in the IA group to the higher number of implanted cells in the brain during early reperfusion (28). …”