The dark side of the force – constraints and complications of cell therapies for stroke

So there might actually be a bad side to stem cells as compared to a lot of survivors waiting breathlessly for stem cells to be proven because stem cells will solve all the stroke problems.
I personally think I will never benefit from stem cells and I figure I have 35-40 years left to go.
http://journal.frontiersin.org/article/10.3389/fneur.2015.00155/full?utm_source=newsletter&utm_medium=email&utm_campaign=Neurology-w35-2015

Johannes Boltze^1,2*, Antje Arnold^3,4, Piotr Walczak^3,4, Jukka Jolkkonen⁵, Lili Cui^5† and Daniel-Christoph Wagner^1†

• ¹Department of Cell Therapy, Fraunhofer-Institute for Cell Therapy and Immunology, Leipzig, Germany
• ²Translational Center for Regenerative Medicine, University of Leipzig, Leipzig, Germany
• ³Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
• ⁴Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA
• ⁵Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland

Cell therapies are increasingly recognized as a promising option to augment the limited therapeutic arsenal available to fight ischemic stroke. During the last two decades, cumulating preclinical evidence has indicated a substantial efficacy for most cell treatment paradigms and first clinical trials are currently underway to assess safety and feasibility in patients. However, the strong and still unmet demand for novel stroke treatment options and exciting findings reported from experimental studies may have drawn our attention away from potential side effects related to cell therapies and the ways by which they are commonly applied. This review summarizes common and less frequent adverse events that have been discovered in preclinical and clinical investigations assessing cell therapies for stroke. Such adverse events range from immunological and neoplastic complications over seizures to cell clotting and cell-induced embolism. It also describes potential complications of clinically applicable administration procedures, detrimental interactions between therapeutic cells, and the pathophysiological environment that they are placed into, as well as problems related to cell manufacturing. Virtually each therapeutic intervention comes at a certain risk for complications. Side effects do therefore not generally compromise the value of cell treatments for stroke, but underestimating such complications might severely limit therapeutic safety and efficacy of cell treatment protocols currently under development. On the other hand, a better understanding will provide opportunities to further improve existing therapeutic strategies and might help to define those circumstances, under which an optimal effect can be realized. Hence, the review eventually discusses strategies and recommendations allowing us to prevent or at least balance potential complications in order to ensure the maximum therapeutic benefit at minimum risk for stroke patients.

Introduction

Therapeutic stem cell research represents one of the most vibrant fields in regenerative medicine. Embryonic, fetal, and adult stem cells are believed to exert multiple therapeutic actions. These range from potential tissue regeneration over the support of local endogenous repair attempts to the beneficial modulation of systemic immune responses. The still ongoing discovery of this tremendous therapeutic potential has fueled the imagination of researchers and clinicians to develop novel therapeutic strategies and to treat disorders, which have been considered untreatable for decades. Among those, ischemic stroke plays a primary role. Stroke is a worldwide predominant cause of death and acquired disability in adulthood (1). The only currently available treatment is thrombolysis, being restricted by a narrow time window (2) and a number of contraindications (3). Together, these limitations exclude the majority of patients from successful and causal treatment. On the other hand, numerous scientific reports corroborated the therapeutic benefit provided by stem cell populations in stroke. This is exemplified by the improvement of neurofunctional deficits (4), reduction of infarct volume, an extension of the time windows for intervention (5, 6), pro-regenerative cerebral reorganization (7), and potentially even limited tissue restoration (8), as well as mitigation of post-stroke neuroinflammation (9). Consequently, first early stage clinical studies are underway to confirm safety and to collect evidence for the therapeutic benefit of stem cell-based treatments in human stroke patients (10).

However, the well-founded enthusiasm for cell therapies and the urgent need for novel therapeutic approaches seem to have drawn our attention away from possible complications of stem cell applications in stroke. Since each therapeutic intervention comes at the risk of undesirable side effects, such side effects would not generally compromise the overall value of stem cell therapies. They could, however, significantly limit the safety, efficacy, as well as successful translation of stem cell-based experimental treatment concepts into clinically available therapies. We therefore argue that potential side effects deserve a closer and more thorough look. Moreover, some side effects might be specific to stroke because important pathophysiological aspects such as blood brain barrier (BBB) breakdown, perilesional hyperexcitability, systemic immunodepression and others differ from those in the other central nervous system (CNS) pathologies. This review summarizes current preclinical and clinical evidence for risks arising from therapeutic use of stem cell populations and the means by which the therapies are commonly applied. It also describes major translational hurdles, which arise from undesirable interactions between the cell transplant and its local pathophysiological environment.

Lots more at link.