Preparing for Future Stem Cell Clinical Trials

  • Keith W. MuirEmail author
Part of the Springer Series in Translational Stroke Research book series (SSTSR)


Clinical trials in stem cell therapy for stroke have predominantly been small, single-centre and safety focused studies, few with blinding or concurrent control groups, and typically with wide treatment time windows and clinical entry criteria. Only recently have trials begun to consider the evolving preclinical evidence base and strategies that might translate this successfully into clinical use. The next few years will witness clinical trials that are likely to establish whether or not there is worthwhile therapeutic potential.

The accumulated experimental evidence has led to two distinct paradigms for cell therapy in stroke. In the first, systemically administered cells are delivered in the acute or early subacute phase, with a mechanism of action that is likely to be predominantly reliant on anti-inflammatory and trophic effects. With intravascular delivery, cells do not enter the central nervous system (CNS) in any significant numbers, if at all, and neither CNS nor systemic engraftment has been established. This approach reflects the great majority of experimental studies. Its likely translational route replicates established acute stroke trial paradigms. Trial designs in this area have had the advantage of evolution since the 1990s such that inclusion and exclusion criteria are well understood, as are trial endpoints.

The second paradigm is of later stage cell delivery to enhance recovery in subacute or chronic stroke. The experimental support is thinner, there being few animal models of this scenario, and there are fewer clinical trials in this time frame from which to draw designs. On the other hand, this represents a huge area of unmet clinical need lacking any very effective intervention.

Both paradigms are being addressed by currently planned or ongoing clinical trials of cell therapy. This chapter will review the main issues that require to be considered.


Clinical trials Stem cells Trial design Placebo 



Action research arm test


Barthel index


Bone marrow-derived mononuclear cells


Central nervous system


Middle cerebral artery occlusion


Modified Rankin Scale


National Institutes of Health Stroke Scale


National Institutes of Neurological Disorders


Preliminary investigation of stem cell effects in stroke


Stem cells as an emerging paradigm in stroke


Transcortical magnetic stimulation


Virtual international stroke trials archive


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute of Neuroscience and PsychologyUniversity of GlasgowGlasgowUK
  2. 2.Queen Elizabeth University HospitalGlasgowUK

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