Bone marrow mononuclear cell therapy in ischaemic stroke: a systematic review
Stroke has emerged as the second most common cause of mortality worldwide.1 Nearly 50% of stroke survivors are left with disabling sequelae. Acute ischaemic stroke (IS) is the most common type of stroke, and only few therapeutic options are available for the same such as the use of tissue plasminogen activator, aspirin, surgical decompression and stroke rehabilitation units.3 Thus, there is a clear need for exploring new therapeutic options. Preclinical studies have shown that bone marrow mononuclear cell (BM‐MNC) therapy has emerged as a potential therapy for the treatment of stroke. BM‐MNCs contain several types of stem cells including hematopoietic stem cells (HSCs)4 and mesenchymal stem cells (MSCs) along with the hematopoietic progenitor and differentiated cells. These multipotent stem cells undergo chemotaxis towards the lesion sites and have the ability to produce and secrete various cytokines and growth factors.5 These mechanisms may suggest the potential for BM‐MNC therapy to act as a therapeutic agent for treating stroke as they are readily available from bone marrow and can be harvested and infused within hours of bone marrow aspiration in acute settings. Several preclinical studies have shown that the treatment with BM‐MNCs can reduce the infarct size and improve the functional outcome.7 BM‐MNC therapy is most commonly used in preclinical and clinical neuroregenerative studies. A recently published meta‐analysis based on single‐arm studies included 14 clinical studies and highlighted the preliminary efficacy of stem cell transplantation for the treatment of stroke.9 However, the result of this study should be read with caution as recovery from stroke is well recognized in its natural history. One pilot comparative study showed that intra‐arterial infusion of BM‐MNCs is safe and feasible and also has some biological influence.10 One recently published large randomized controlled trial has shown that BM‐MNC therapy is safe through the intravenous route but no added benefit when intervention was given within 7–30 days of the onset of stroke.11
However, the literature suggests conflicting evidences for the efficacy of BM‐MNC therapy in patients with stroke which may be explained on the basis of significant heterogeneity, selection bias, publication bias and investigator bias. Therefore, more randomized controlled trials (RCTs) are required for informed decision‐making based on more robust evidences with respect to the use of BM‐MNC therapy for patients with IS. A meta‐analysis may help in building such higher quality evidence and planning focussed, promising and adequately powered RCTs. Therefore, we conducted a meta‐analysis to summarize the clinical studies in order to draw necessary evidence to plan future RCTs for testing the efficacy of BM‐MNC intervention in patients with IS.