title: Increasing Dose of Autologous Bone Marrow Mononuclear Cells Transplantation Is Related to Stroke Outcome: Results from a Pooled Analysis of Two Clinical Trials.
abstract: Background and Purpose. BM-MNC transplantation improves recovery in experimental models of ischemic stroke. Clinical trials are ongoing to test efficacy in stroke patients. However, whether cell dose is related to outcomes is not known. Methods. We performed a pooling data analysis of two pilot clinical trials with autologous BM-MNCs transplantation in ischemic stroke patients. Cell dose and route were analyzed to evaluate their relation to good outcome (m-Rankin scale [mRS] score 0-2) at 6 months. Results. Twenty-two patients were included. A median of 153 × 10(6) (±121 × 10(6)) BM-MNCs was injected. Intra-arterial route was used in 77.3% of cases. A higher number of cells injected were associated with better outcomes at 180 days (390 × 10(6) [320-422] BM-MNCs injected in those patients with mRS of 0-2 at 6 months versus 130 × 10(6) [89-210] in those patients with mRS 3-6, p = 0.015). In the intra-arterially treated patients, a strong correlation between dose of cells and disability was found (r = -0.63, p = 0.006). A cut point of 310 × 10(6) injected cells predicted good outcome with 80% sensitivity and 88.2% specificity. Conclusions. Similar to preclinical studies, a higher dose of autologous BM-MNC was related to better outcome in stroke patients, especially when more than 310 × 10(6) cells are injected. Further interventional studies are warranted to confirm these data.
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain; Instituto de Biomedicina de Sevilla-IBiS, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Francisco
authors.identifier: 0000-0001-8613-2909
authors.initials: F
authors.lastname: Moniche
authors.affiliation: Instituto de Ciências Biomédicas, Federal University of Rio de Janeiro, 21044-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Paulo Henrique
authors.identifier: 0000-0003-0091-9714
authors.initials: PH
authors.lastname: Rosado-de-Castro
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain; Instituto de Biomedicina de Sevilla-IBiS, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Escudero
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain; Instituto de Biomedicina de Sevilla-IBiS, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Zapata
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain; Instituto de Biomedicina de Sevilla-IBiS, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: de la Torre Laviana
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, 21044-020 Rio de Janeiro, RJ, Brazil.
authors.forename: Rosalia
authors.identifier: 0000-0002-1798-9930
authors.initials: R
authors.lastname: Mendez-Otero
authors.affiliation: Department of Hematology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Carmona
authors.affiliation: Department of Radiology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Piñero
authors.affiliation: Neurovascular Research Laboratory, Institut de Recerca Vall d'Hebron, Hospital Vall d'Hebron, 08035 Barcelona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bustamante
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Lebrato
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Cabezas
authors.affiliation: Department of Radiology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: D'Or Institute for Research and Education, 22281-100 Rio de Janeiro, RJ, Brazil.
authors.forename: Grabriel R
authors.initials: GR
authors.lastname: de Freitas
authors.affiliation: Instituto de Biomedicina de Sevilla-IBiS, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain; Neurovascular Research Laboratory, Institut de Recerca Vall d'Hebron, Hospital Vall d'Hebron, 08035 Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner