Embryonic stem (ES) cell therapies are often promoted as the optimal stem cell source for regenerative medicine applications because of their ability to develop into any tissue in the body.
Unfortunately, ES cell applications are currently limited by ethical, political, biological and regulatory hurdles.
However, multipotent non-ES cells are available in large numbers in umbilical cord blood (CB).
CB stem cells are capable of giving rise to hematopoietic, epithelial, endothelial and neural tissues both in vitro and in vivo.
Thus, CB stem cells are amenable to treat a wide variety of diseases including cardiovascular, ophthalmic, orthopaedic, neurological and endocrine diseases.
In addition, the recent use of CB in several regenerative medicine clinical studies has demonstrated its pluripotent nature.
The brain is extremely sensitive to hypoxia and some degree of tissue death is likely from stroke.
At a relatively young age the brain loses most of its plasticity so any significant tissue death can be profoundly devastating.
Interestingly, in young children the brain is very plastic and very large portions of the brain can be removed (such as removal of tumours or hemispherectomy for severe seizures) with relatively low to no noticeable long term neurological damage.
These facts suggest that younger neural cells, which could be generated by differentiation from CB, might have a greater capacity to regenerate the injured brain.
Nowhere has the potential significance of CB stem cell therapy for the treatment of neurological disease been greater than in this area of stroke therapy.
As early as 2001, it was demonstrated that the infusion of CB stem cells into rats in the commonly used middle carotid artery occlusion (MCAO) model of stroke could reverse many of the physical and behavioural deficits associated with this disease.
Studies demonstrated that direct injection of the stem cells into the brain was not required, and in fact, beneficial effects could be observed even if the stem cells did not actually home into the target organ (probably via the release of growth and repair factors triggered by the anoxia).
The beneficial effects seemed to be dose-dependent and could reduce the size of the infarcted tissue.
It appeared that multiple progenitor populations in CB were capable of mediating these effects.
Significantly, unlike current pharmacological interventions that require treatment within the first few hours after stroke, CB stem cell therapies were effective up to 48 h after the thrombotic event.
In fact, administration of CB stem cells immediately after the ischemic event may be detrimental in that the inflammatory milieu may be toxic to the administered stem cells.
The majority of reported studies have shown that CB administration in stroke models resulted in some degree of therapeutic benefit with no adverse effects.
Neuroprotective effects as well as functional or behavioural improvements from CB therapies have been widely reported.
Neurological improvement was accompanied by decreased inflammatory cytokines, by neuron rescue/reduced ischemic volume, as well as by lowered parenchymal levels of granulocytic/monocytic infiltration and astrocytic/ microglial activation.
Thus, the mechanisms behind the observed beneficial effects afforded by CB therapies included reduced inflammation, protection of nervous tissue from apoptosis and nerve fibre reorganisation.
These observations are particularly encouraging as it implies that CB therapy can mediate both direct restorative effects to the brain as well as tropic neuroprotection.
Many of the published studies lend support to this trophic role, in that several investigators reported neural protection with little to no detection of CB cells engrafted in the brain.
The level of engraftment in the brain appeared to be a function of the route of CB administration.
When CB was administered intravenously, little or no CB migration to the brain was found.
However, when CB was given intraperitoneally there was evidence of neural restorative effects.
Early studies have also shown benefit in animal models of haemorrhagic (as opposed to embolic) stroke.
For additional information, the reader is referred to the recent review on cell therapies for stroke found in reference.
In addition to stroke, CB stem cells have been used in other nervous system injury models, two of which have now instigated clinical trials.
Scientists have demonstrated that intravenous administration of CB mononuclear cells could be used to treat traumatic brain injury in a rat model.
In this model the CB cells were observed to enter the brain, selectively migrate to the damaged region of the brain, express neural markers and reduce neurological damage.
Similarly, CB stem cell transplant could also alleviate symptoms of newborn cerebral palsy in a rat model, with improved neurological effects.
These observations have now been turned into clinical therapies.
Cord Blood Registry (a private family CB bank) has released 50 CB stem cell units for autologous use in the treatment of cerebral palsy, anoxic and traumatic brain injury in a clinical study at Duke University.
Early, albeit anecdotal, reports have indicated beneficial effects from the CB mono- nuclear cells infusions.
Several investigators have begun planning clinical trials to treat children with hypoxic/ischaemic and traumatic brain injury by utilising autologous CB stem cell infusions.
The observation that CB stem cells can become different types of nervous cells extends its utility to other areas of neurological damage, including spinal cord injury.
Spinal cord injured rats infused with CB stem cells have shown significant improvements 5 d post-treatment compared to untreated animals.
The CB stem cells were observed at the site of injury but not at uninjured regions of the spinal cord.
This finding is supported by another study demon- strating that CB stem cells transplanted into spinal cord injured animals differentiated into various neural cells, improving axonal regeneration and motor function.
Significantly, in a recently reported clinical use of CB stem cells to treat a patient with a spinal cord injury it was stated that transplantation of CB cells improved her sensory perception and mobility in the hip and thigh regions.
Both computed tomography and magnetic resonance imaging studies revealed regeneration of the spinal cord at the injury site.
Since the CB stem cells were allogeneic in origin it will be significant to determine if immune rejection or other immune-mediated problems occur that might jeopardize the early improvement.
Neither additional patients nor additional studies in this area have been reported.
However, the use of CB stem cells for spinal cord injury seems to be the next logical clinical trial.
Large numbers of children are unfortunate enough to suffer a spinal cord injury at an early age (e.g. diving into a pool, car accidents, falls, etc) and it would be expected that a significant number would have autologous CB banked and available for treatment.