Cord Blood as a Treatment for Stroke

Abstract

Over the last few decades, there has been an explosion in stem cell research. The investigation of umbilical cord blood (UCB) cells as a treatment for stroke is even more recent. Ease of collection and the ability to maintain their stem cell properties post-cryopreservation made these cells very attractive candidates for treatment development initially. UCB cells have many advantages including a wide variety of cell types present, including hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, lymphocytes, and monocytes, which enhances their ability to modulate multiple targets impacted by neurodegenerative processes. Although the precise mechanisms of action are still being researched, UCB cells have been shown to benefit functional recovery and also reduce infarct size post-stroke. They have also demonstrated an ability to provide these benefits when administered peripherally and within 24–48 h post-stroke, which immensely expands the current treatment window of 3–4 h for tissue plasminogen activator. This chapter highlights the current research with UCB cells in the development of a novel treatment for stroke and demonstrates the great therapeutic potential of these cells.

Conclusions

The evidence presented suggests that the UCB cells have a great deal of potential as a future treatment for stroke, both ischemic and hemorrhagic, in young and adult alike. By virtue of the fact that they are living cells producing a variety of different factors, these cells have been shown to have pleiotropic effects. However, the stroke field is rife with examples of promising pre-clinical experimental treatments that have not panned out in clinical trial. There are studies which have not reproduced these positive outcomes in both adult models (Makinen et al. 2006; Nystedt et al. 2006; Zawadzka et al. 2009; Riegelsberger et al. 2011) and neonatal models (De Paula et al. 2009). There are no obvious differences between these studies and the studies presented earlier showing therapeutic benefit although extensive protocols for cell preparation and storage are not provided in most reports. It is imperative that we understand why these differences exist and their implications for the long-term success of this cell therapy.

There are also other questions that will need to be addressed as we move toward the clinic. The cells appear to be efficacious across the lifespan, but it is too early to draw that conclusion. Almost all of the studies in the adult are in younger adults and not the aged. While the cells have a demonstrated ability to increase proliferation in the subgranular zone of the hippocampus and increase density of dendritic spines (Bachstetter et al. 2008; Shahaduzzaman et al. 2013) in the aged rat, they have not yet been shown to improve stroke outcome in an aged animal.

All the studies discussed here have used human cells in a rodent model of stroke. Xenografting has its own immunologic issues. It is not particularly surprising that the UCB cells are rarely observed surviving in the host even when very stringent immune suppression protocols are employed; it is, perhaps, more surprising that the cells still seem to have such profound effects. When these cells are administered to a human stroke patient, however, it is not clear how much immune suppression or HLA matching will be required. These studies are best addressed in a larger animal model. There is one report in which 114 patients suffering from with 13 varied neurologic injuries or diseases all received allogeneic UCB MSC transplants with no preconditioning, HLA matching or immune suppression (Yang et al. 2010). All hematologic and immunologic parameters and serum chemistries were in the normal range for these patients. The worst adverse events reported were 3 % of the patients experienced headaches and 1 % developed a fever. There was no report on whether any of the patients experiences any benefit from the treatment and the number of patients with any specific neurologic condition was small. Further studies are still needed.

Even given these caveats, the bulk of the evidence suggests that UCB cells may have therapeutic benefit. Multiple groups using different models of cerebral ischemia and hemorrhage , different UCB cell preparations, different routes, different cell doses, differences in timing of cell delivery and different tests of motor and cognitive function have demonstrated efficacy of this experimental treatment. Cautious optimism is warranted as preclinical testing and future clinical trials move forward.