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

Abstract

IntroductionBased on many preclinical and small clinical trials, stem cells can help stroke patient with the possibility of replacing the cells and supporting the remaining cells. The aim of this study was to evaluate the safety and feasibility of bone marrow mononuclear (BMMN) stem cell transplantation in subacute ischemic stroke patients.Materials and methodsThirty-nine (n = 39) patients with subacute ischemic cerebral infarct due to large artery occlusion in the middle cerebral artery (MCA) territory were recruited. They were distributed into two groups: first group (n = 21) served as an experimental group, which received intra-arterial (IA) mononuclear stem cells (bone marrow-derived mononuclear cell), while the other group (n = 18) served as a control group. All the patients were evaluated clinically by National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel Index, modified and standardized Arabic version of the Comprehensive Aphasia Test, and radiological for 12 months.ResultsThe stem cell-treated group showed better improvement, but it was not significant when compared with the non-treated group. The volume of infarction changes at the end of the study was non-significant between both the groups. There was no, or minimal, adverse reactions in stem cell-treated group.ConclusionThe study results suggest that autologous BMMN stem cell IA transplantation in subacute MCA ischemic stroke patients is safe with very minimal hazards, but no significant improvement of motor, language disturbance, or infarction volume was detected in stem cell-treated group compared with the non-treated group.

Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men

“…The IA route has already been validated in a large animal model and transplantation of even large MSCs was safe and therapeutic in a canine ischemia model (Chung et al, 2009). There were also no adverse events as a result of IA delivery of bone marrow mononuclear cells in subacute ischemic stroke patients (Ghali, Yousef, Ragab, & ElZamarany, 2016).…”

“…The IA route has already been validated in a large animal model and transplantation of even large MSCs was safe and therapeutic in a canine ischemia model (Chung et al 2009). There were also no adverse events as a result of IA delivery of bone marrow mononuclear cells in subacute ischemic stroke patients (Ghali et al 2016). However, the effective diapedesis in diseases without or with little neuroinflammatory component, such as dysmyelination and related neurodegenerative disorders, is still unresolved and thus, this route of delivery also may have its limitations.…”

Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

“…Cell transplantation after a week for up to 6 months is considered to be sub-acute treatment [ 2 , 3 , 5 , 8 , 11 , 13 , 14 , 15 , 17 , 20 , 22 , 24 , 26 , 27 , 28 , 34 , 36 , 42 ]. In addition to BMMNCs, autologous BMSCs are used for ex-vivo expansion within a time frame of approximately 1 month.…”

“…Lately, stem cell therapy has been recognized as a promising strategy that functionally enhances recovery from ischemic stroke. Thus, a variety of cells, including bone marrow mononuclear cells (BMMNCs) [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], bone marrow/adipose-derived stem/stromal cells (BMSCs/ADMSCs) [ 4 , 6 , 7 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], umbilical cord blood cells (UCBCs) and hematopoietic stem cells [ 32 , 33 , 34 , 35 , 36 , 37 ], neural stem cells (NSCs) [ 34 , 36 , 38 , 39 , 40 , 41 , 42 , 43 ], olfactory ensheathing cells (OECs) [ 38 ], and fetal porcine cells [ 44 ], have been explored as candidate donors. Animal studies have indicated that such cells may ameliorate the neurological deficits that follow cerebral stroke, and some have been tested in clinical trials with somewhat favorable results.…”

Cell therapy for ischemic stroke: Are differences in preclinical and clinical study design responsible for the translational loss of efficacy?

“…5,37,38 The current advances in recanalization approaches may lead to increasing numbers of patients receiving cell therapy immediately after recanalization in the future, warranting the use of a transient stroke model for preclinical evaluation regardless of the targeted time point of cell administration, and would allow cell transplantation in a more acute stage after stroke onset in clinical trials. However, only a limited number of patients experience prompt recanalization, thus the permanent occlusion models might better reflect the presentday clinical situation except for intra-arterial cell transplantation.…”