Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke

Abstract

Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra-arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open-label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty-two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age>80 years (n=19); medical instability (n=17), and significant carotid stenosis (n=13). The procedure was well tolerated in all patients, and no significant treatment-related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6-month follow-up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials.

Keywords: CD34+; Intra-arterial; Ischemic stroke; Stem cells.

©AlphaMed Press.

Figures

Figure 1.

Patient flow. Abbreviations: PACS, partial anterior circulation stroke; TACS, total anterior circulation stroke.

Figure 2.

National Institutes of Health Stroke Scale scores on admission and at days 0–180.

Figure 3.

Modified Rankin Scores on admission and at days 0–180.

Figure 4.

Findings from imaging studies. (A): Percentage of change in infarct volume from day 0 to 180 for patients 1–5. (B): Baseline diffusion weighted magnetic resonance images for patients 1–5 (shown left to right). (C): Angiographic image of intra-arterial catheter delivery of cells to M1 segment (blue arrow) of left middle cerebral artery.

Figure 5.

Serial brain imaging from baseline to day 180 in patients 1–5. (A): Serial MRI scans of patient 1 showing progressive maturation of a left middle cerebral artery (MCA) infarct. (B): Baseline CT and subsequent MRI scans of patient 2 showing progressive maturation of a right MCA infarct. (C): Serial MRI scans patient 3 showing progressive maturation of a right MCA infarct. (D): Serial MRI scans of patient 4 showing progressive maturation of a left MCA infarct. (E): Serial MRI scans of patient 5 showing progressive maturation of a left MCA infarct. Abbreviations: CT, computed tomography; DW, diffusion weighted; MRI, magnetic resonance imaging.

Figure 5.

Serial brain imaging from baseline to day 180 in patients 1–5. (A): Serial MRI scans of patient 1 showing progressive maturation of a left middle cerebral artery (MCA) infarct. (B): Baseline CT and subsequent MRI scans of patient 2 showing progressive maturation of a right MCA infarct. (C): Serial MRI scans patient 3 showing progressive maturation of a right MCA infarct. (D): Serial MRI scans of patient 4 showing progressive maturation of a left MCA infarct. (E): Serial MRI scans of patient 5 showing progressive maturation of a left MCA infarct. Abbreviations: CT, computed tomography; DW, diffusion weighted; MRI, magnetic resonance imaging.