You are hereNovember 7, 2014 | Haematopoetic Stem Cells
Autologous Hematopoietic Cell Therapy for Stroke Assessed in Humans
Review of “Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke” from SCTM by Stuart P. Atkinson
The success of stem cell therapies for ischemic stroke in non-human models has encouraged the translation of said therapies to humans. Treatment with CD34+ stem/progenitor cells, the main source of hematopoietic and endothelial cell precursors, improves functional recovery and reduces infarct size in rodent models [1, 2], and in a trial using bone marrow mononuclear cells (BMMNCs), CD34+ cell concentration correlated to functional outcome . Now the group of Jeremy Chataway (University College London, London, United Kingdom) report in Stem Cells TM on their trial of autologous CD34+-selected cells transplanted via intra-arterial delivery at an early time point after stroke in human patients . This small trial demonstrates big results; good tolerance of therapy, no adverse reactions, and improvements in clinical functional scores and reductions in lesion volume at 6 months.
This proof of concept study of autologous CD34+ stem/progenitor cells took place in 5 patients (from a group of 76 patients) with acute severe ischemic stroke. After collection of bone marrow aspirate within 7 days of the stroke event, the group immunoselected cells and re-infused them intra-arterially within 1 or 2 days, with clinical outcome measures and other studies performed up to 180 days after infusion. The early time point of treatment was critical to the study; transplanted cells are likely to have a trophic supporting role as grafted cell numbers are low, and so their introduction soon after the ischemic event was deemed to be a vitally important facet of this mode of therapy. The group noted no complications linked to the intervention and all patients tolerated the stem cell therapy well. Encouragingly, all patients demonstrated improvements in clinical functional scores (Modified Rankin Score and NIH Stroke Scale) and a reduction in lesion volume by 180 days, with a mean percentage change from baseline of 26% (See Figure). While the study had no control group and was not powered to be able to detect efficacy, the authors observed a trend toward functional improvement, with no sign of post-intervention stroke, vascular malformation, or tumor formation.
This trial suggests that this mode of intervention is both possible and safe, even though the promising clinical results observed in this small number of patients are not an unusual part of the natural history of stroke recovery. The authors hope to instigate further studies encouraged by these findings to assess eligibility criteria, dosage, delivery site, timing, and surrogate imaging markers of outcome, before moving into larger clinical trials.
- Shyu WC, Lin SZ, Chiang MF, et al. Intracerebral peripheral blood stem cell (CD34+) implantation induces neuroplasticity by enhancing beta1 integrin-mediated angiogenesis in chronic stroke rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 2006;26:3444-3453.
- Taguchi A, Soma T, Tanaka H, et al. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. The Journal of clinical investigation 2004;114:330-338.
- Moniche F, Gonzalez A, Gonzalez-Marcos JR, et al. Intra-arterial bone marrow mononuclear cells in ischemic stroke: a pilot clinical trial. Stroke 2012;43:2242-2244.
- Banerjee S, Bentley P, Hamady M, et al. Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke. Stem Cells Translational Medicine 2014.