Intra-Arterial Infusion of Autologous Bone Marrow Mononuclear Cells in Patients with Moderate to Severe Middle Cerebral Artery Acute Ischemic Stroke

Abstract

Transplantation of autologous bone marrow mononuclear cells (BMMCs) has been proven safe in animal and human studies. However, there are very few studies in stroke patients. In this study, intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infarcts. The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits, in whom treatment could be initiated between 3 and 7 days after stroke onset. Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere. Safety analysis (primary endpoint) during the 6-month follow-up assessed death, any serious clinical events, neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) scores, seizures, epileptogenic activity on electroencephalogram, and neuroimaging complications including new ischemic, hemorrhagic, or neoplastic lesions. Satisfactory clinical improvement (secondary endpoint) at 90 days was defined according to the pretreatment NIHSS scores as follows: modified Rankin Scale score of 0 in patients with NIHSS <8, modified Rankin Scale scores of 0-1 in patients with NIHSS 8-14, or modified Rankin Scale scores 0-2 in patients with NIHSS >14. Good clinical outcome was defined as mRS ≤2 at 90 days. Serial clinical, laboratory, electroencephalogram, and imaging evaluations showed no procedure-related adverse events. Satisfactory clinical improvement occurred in 6/20 (30%) patients at 90 days. Eight patients (40%) showed a good clinical outcome. Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes. No cases of intrahospital mortality were seen in this pilot trial. Larger prospective randomized trials are warranted to assess the efficacy of this treatment approach.

Strategies for CNS repair following TBI

“…These results are consistent with the safe administration of BM-MNC in the acute (24-72 hours) treatment of strokes in adult population (Savitz et al, 2011). Intra-arterial administration of BM-MNC has also been performed in stroke patients with infusion into the middle cerebral artery (Friedrich et al, 2012;Moniche et al, 2012). Additional trials evaluating the safety of intra-arterial infusion of CD34+ cell populations and MSC have been completed (Banerjee et al, 2014;Bang et al, 2005).…”

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

“…These results agreed with that of the previous work by Bhasin et al (18); however, they reported that the stem cell group showed more functional improvement, but they did not find significant difference in functional brain MRI between experimental and control groups at 8 weeks and 6 months post-treatment. Also, Friedrich et al (22) reported non-significant difference in infarct volumes or infarct densities between groups with and without clinical improvement.…”

Stem cell therapies in preclinical models of stroke associated with aging

“…Transplantation of autologous bone marrow-derived MSCs in pilot studies has been proven safe in human patients with acute middle cerebral artery infarcts (Bang et al, 2005; Battistella et al, 2011; Savitz et al, 2011; Friedrich et al, 2012; Moniche et al, 2012; Banerjee et al, 2014). Moreover, improvements of neurological recovery were noted (Bang et al, 2005; Battistella et al, 2011; Savitz et al, 2011; Friedrich et al, 2012; Moniche et al, 2012; Banerjee et al, 2014). Unfortunately, these studies lacked appropriate control groups, which limits conclusions around the efficacy of cell therapy.…”