Conditions

Stroke

Stroke is a leading cause of mortality and is estimated to cause 5 million deaths per year worldwide. On average an American will suffer a stroke every 40 seconds and every year approximately 795,000 Americans have a new or recurrent stroke. Currently, there are limited conventional treatments for acute stroke such as intravenous tissue plasminogen activator which must be administered in a narrow window of 4.5 hours after the incident and even fewer treatment options for chronic stroke. Despite recent advancements in therapeutic options and rehabilitation strategies stroke remains a significant cause of disability.

Stem cell infusion is a promising novel therapy and is becoming recognized as a valid treatment option in both acute and chronic stroke due to human clinical studies demonstrating its safety and effectiveness. Stem cells from various tissue types have been investigated to treat stroke patients including bone marrow, adipose, and umbilical derived stem cells. The use of bone marrow derived stem cells has been the major focus within this area of research. However, due to the invasiveness of the procedure to harvest bone marrow stem cells there is growing interest in other cell types.

Stem cells can be administered in a number of different ways. Common routes of administration used in stroke research include intravenous, intra-arterial (injected into arteries), intracerebral (surgically implanted into brain) and intrathecal (injected into the spinal canal). The advantage of intravenous injection is that it is less invasive and does not require sedation and/or surgery. Results from published research suggest that intravenous injection of stem cells is safe and effective.

Based on early human clinical trials there appears to be a strong argument for the safe and effective use of stem cell therapy in the treatment of stroke. While we wait for phase II/III trials the current data is encouraging and supports use of stem cell therapy in the clinical setting.

Proven Benefits From Early Human Clinical Trials of Stem Cell Therapy in Stroke:

• Significant improvement in various neurological assessment tools including National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI) and modified Rankin Scale (mRS) (Levy et al, Vahidy et al, Ouyang et al, Laskowtiz et al, Xue et al, Taguchi et al)
• Reduction in neurological impairment (Xue et al)
• Improvement in level of disability and independence (Xue et al)
• Increased structural integrity and coherence of axon fibers in the brain suggesting microstructural repair (Vahidy et al)
• Improved blood flow and increased metabolic activity of brain (Taguchi et al)
• Improved quality of life (Ouyang et al)

Specific Conclusions From Selected Studies:

“Intravenous transfusion of allogeneic ischemia-tolerant mesenchymal stem cell in patients with chronic stroke and substantial functional deficits was safe and suggested behavioral gains.”

• Study of Safety and Preliminary Efficacy of Intravenous Allogeneic Mesenchymal Stem Cells in Chronic Stroke. (Levy et al, 2019)

“Bone marrow harvest and infusion of bone marrow derived stem cells is “safe and feasible in patients with acute ischemic stroke.”

• Intravenous Bone Marrow Mononuclear Cells for Acute Ischemic Stroke: Safety, Feasibility, and Effect Size from a Phase I Clinical Trial. (Vahidy et al, 2019)

“Stem cell transplantation can significantly improve neurological deficits and quality of life in patients with ischemic stroke, without severe adverse reactions.”

• Meta-Analysis of the Safety and Efficacy of Stem Cell Therapies for Ischemic Stroke in Preclinical and Clinical Studies. (Ouyang et al, 2019)

“UCB in adults after acute ischemic stroke is safe, well tolerated and feasible. In addition, improvements in functional outcomes were observed in all participants 3 months post-infusion.”

• Allogeneic Umbilical Cord Blood Infusion for Adults with Ischemic Stroke: Clinical Outcomes from a Phase 1 Safety Study. (Laskowitz et al, 2018)

“Our analysis verified the safety and efficacy of MSC therapy for ischemic stroke (IS). It significantly mitigated neurological defects and improved life quality of IS patients, without causing serious adverse events.”

• Mesenchymal stem cell transplantation as an effective treatment strategy for ischemic stroke in Asia: a meta-analysis of controlled trials. (Xue et al, 2018)

“Stem cell therapy with “multipotent adult progenitor cells were safe and well tolerated in patients with acute ischemic stroke.”

• Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. (Hess et al, 2017)

“Our study demonstrates that intravenous administration of autologous bone marrow mononuclear cells to patients with severe embolic stroke was feasible and safe. Positive results and trends favoring neurological recovery and improvement in cerebral blood flow and metabolism in post-stroke patients receiving therapy underscore the potential of this approach.”

• Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients. (Taguchi et al, 2015)

For additional information on stem cell therapy in stroke and more details regarding these studies please visit our Research Archive.

SOURCES:

• Bhatia, V., Gupta, V., Khurana, D., Sharma, R. R., & Khandelwal, N. (2018). Randomized assessment of the safety and efficacy of intra-arterial infusion of autologous stem cells in subacute ischemic stroke. American Journal of Neuroradiology, 39(5), 899–904. https://doi.org/10.3174/ajnr.A5586
• Vahidy, F. S., Haque, M. E., Rahbar, M. H., Zhu, H., Rowan, P., Aisiku, I. P., … Savitz, S. I. (2019). Intravenous Bone Marrow Mononuclear Cells for Acute Ischemic Stroke: Safety, Feasibility, and Effect Size from a Phase I Clinical Trial. STEM CELLS. https://doi.org/10.1002/stem.3080
• https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2019/02/15/14/39/aha-2019-heart-disease-and-stroke-statistics
• Taguchi, A., Sakai, C., Soma, T., Kasahara, Y., Stern, D. M., Kajimoto, K., … Nagatsuka, K. (2015). Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients. Stem Cells and Development, 24(19), 2207–2218. https://doi.org/10.1089/scd.2015.0160