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New Hematopoietic Stem Cell Therapy Assessed in Stroke

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Review of “Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke” from Stem Cells TM by Stuart P. Atkinson

Stem cell therapies aimed to reduce tissue injury progression and enhance functional recovery in patients with stroke have met with some success in animal models. Selected CD34+ bone marrow mononuclear cells (BMMNCs) are a promising cell population [1, 2], while Granulocyte-colony stimulating factor (G-CSF), used to mobilize CD34+ cells into the peripheral circulation, can improve outcomes in rodent models of stroke [3, 4]. Combining this knowledge, the group of Soma Banerjee (Imperial College Healthcare National Health Services Trust, London, United Kingdom) aimed to establish the safety and feasibility of autologous bone marrow-derived CD34+ selected stem/progenitor cell therapy in patients with severe ischemic stroke [5].

From a total of 76 patients considered, 5 suitable patients received the CD34+ cell transplants. The process followed with said patients started with bone marrow aspirate collection, followed by immunoselection of CD34+ cells, and then reinfusion at day 1 or 2 directly via the intra-arterial route. All patients tolerated the procedure well and presented with no complications, recurrent strokes or neurologic deterioration. Encouragingly, all patients improved by day 180 as measured by the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Score (mRS) and all demonstrated a reduction in the lesion volume relative to baseline in all patients at the final follow-up examination. Qualitative assessment of Magnetic resonance imaging (MRI) demonstrated the typical evolution of cerebral infarction with no evidence of new lesions.

This study demonstrates the safety and feasibility of direct intra-arterial infusion of autologous CD34+ selected cells for the treatment of stroke. However, even though all patients showed improvements in clinical scores and reductions in lesion volume, efficacy could not be examined due to the small number of patients recruited. Larger studies are required to further examine CD34+ cells in the treatment for stroke and future trials will hope to assess dosage, different methods of delivery, as well as tracking cells post-transplant and understanding the mechanisms of action.

References

  1. 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.
  2. 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.
  3. Shyu WC, Lin SZ, Yang HI, et al. Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 2004;110:1847-1854.
  4. Schabitz WR, Kollmar R, Schwaninger M, et al. Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke 2003;34:745-751.
  5. Banerjee S, Bentley P, Hamady M, et al. Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke. Stem Cells Translational Medicine 2014;