Clinical trial design for stem cell therapies in stroke: What have we learned?

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Muir, Keith W. (2017)

Stem cells of various sources have been investigated in a series of small, safety and feasibility-focused studies over the past 15 years. Understanding of mechanisms of action has evolved and the trial paradigms have become focused on two different approaches – one being an early subacute delivery of cells to reduce acute tissue injury and modify the tissue environment in a direction favourable to reparative processes (for example by being anti-inflammatory, anti-apoptotic, and encouraging endogenous stem cell mobilisation); the other exploring later delivery of cells during the recovery phase after stroke to modulate the local environment in favour of angiogenesis and neurogenesis. The former approach has generally investigated intravenous or intra-arterial delivery of cells with an expected paracrine mode of action and no expected engraftment within the brain. The latter has explored direct intracerebral implantation adjacent to the infarct. Several relevant trials have been conducted, including two controlled trials of intravenously delivered bone marrow-derived cells in the early subacute stage, and two small single-arm phase 1 trials of intracerebrally implanted cells. The findings of these studies and their implications for future trial design are considered.
  • References (61)
    61 references, page 1 of 7

    1. Krishnamurthi RV, Feigin VL, Forouzanfar MH, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 2013; 1(5): e259-81.

    2. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384(9958): 1929-35.

    3. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016; 387(10029): 1723-31.

    4. Morris S, Hunter RM, Ramsay AI, et al. Impact of centralising acute stroke services in English metropolitan areas on mortality and length of hospital stay: difference-in-differences analysis. BMJ 2014; 349: g4757.

    5. Kalladka D, Muir KW. Stem cell therapy in stroke: designing clinical trials. Neurochem Int 2011; 59(3): 367-70.

    6. Savitz SI. Developing Cellular Therapies for Stroke. Stroke 2015; 46(7): 2026-31.

    7. Koch P, Kokaia Z, Lindvall O, Brustle O. Emerging concepts in neural stem cell research: autologous repair and cell-based disease modelling. Lancet Neurol 2009; 8(9): 819-29.

    8. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature 2006; 441(7097): 1094-6.

    9. Saver JL. Time is brain--quantified. Stroke 2006; 37(1): 263-6.

    10. Muir KW, Tyrrell P, Sattar N, Warburton E. Inflammation and ischaemic stroke. Current Opinion in Neurology 2007; 20(3): 334-42.

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