title: 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.
authors.affiliation: Hospital São Lucas, Porto Alegre, Brazil. mfriedrich@terra.com.br
authors.forename: Maurício A G
authors.initials: MA
authors.lastname: Friedrich
authors.forename: Maurer P
authors.initials: MP
authors.lastname: Martins
authors.forename: Mariana D
authors.initials: MD
authors.lastname: Araújo
authors.forename: Charles
authors.initials: C
authors.lastname: Klamt
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vedolin
authors.forename: Bernardo
authors.initials: B
authors.lastname: Garicochea
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Raupp
authors.forename: Jeber
authors.initials: J
authors.lastname: Sartori El Ammar
authors.forename: Denise Cantarelli
authors.initials: DC
authors.lastname: Machado
authors.forename: Jaderson C da
authors.initials: JC
authors.lastname: Costa
authors.forename: Raul G
authors.initials: RG
authors.lastname: Nogueira
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Rosado-de-Castro
authors.forename: Rosalia
authors.initials: R
authors.lastname: Mendez-Otero
authors.forename: Gabriel R de
authors.initials: GR
authors.lastname: Freitas
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000601:surgery*; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies