Stem cell therapy for cerebral palsy
Updates on the prospects for stem cell therapy in cerebral palsy (CP) have been provided recurrently in scientific journals and meetings for more than 10 years. There have been definite advances in the understanding of the different types of stem cell, and in methods that can induce embryonic like pluripotent stem cells by reprogramming mature cells. Yet the messages seem to remain essentially unchanged: the mechanisms of action, optimal type of stem cells, method of administration and dose are still unclear. Much more knowledge is required concerning the biology of stem cells, cell differentiation, and intrinsic neural cell proliferation; relevant animal models of CP are wanting (though some recent ones might prove pertinent) safety and efficacy need to be more rigorously addressed. In sum, stem cells are promising, but clearly not ready even to be assessed for their potential contribution to management of individuals with CP. In parallel, media coverage has stimulated continuing public interest for stem cell treatment in CP. Articles in major and local newspapers have generally conveyed positive messages more often than neutral or negative ones, or ones cautious of risks. They have often uncritically portrayed stem cells as a viable treatment option, emphasizing benefits experienced or anticipated by patients and family members seeking services proposed by 'stem cell clinics' Such clinics, which operate in unregulated settings, often (unverifiably) claim to re inject patients with their own stem cells in a bid to treat conditions ranging from spinal cord injury to Alzheimer's disease. These practices are associated with unacceptable morbidity and mortality, and clinical trials which might lead eventually to sound therapeutic transplantation of stem cells are still in an early phase. Meanwhile, basic stem cell research has opened other important avenues that might inform the understanding and management of CP. Increasing mastery of pluripotent stem cell technologies has resulted in designing self organizing models of neural cell specialization, which recapitulate the molecular and cellular events that are thought to occur in vivo in the developing human brain. These include specification of different parts of the central nervous system, refinement of cerebral cortex cytoarchitecture in space and in time, neurite outgrowth, emergence of membrane excitability, and circuit formation through synaptogenesis. Alternative development of various aetiologies and potential compensatory mechanisms such as observed in CP may be better understood in this way. It has also become possible to generate similar modelling of cortical development based on induced pluripotent stem cells that are derived from patients with specific brain alterations of genetic origin. This may apply to 'simple' genetic defects e.g. point mutations, the stem cell models reproducing features that are potentially related to the pathogenesis of the neurogenetic disease. Hopefully, the relevance to CP of recently identified genes involved in human specific features of brain development can thus be determined. This approach may also provide insights into the mechanisms underlying more complex genetic disorders possibly related to some forms of CP, which are difficult to recapitulate with animal models. Furthermore, though much attention has understandably been directed towards the brain, the recent documentation of markedly reduced numbers of quiescent adult muscle stem cells, known as satellite cells, in contractured muscles of children with CP may also have therapeutic implications. As precursors, satellite cells play a role in skeletal muscle growth and regeneration. Reduced numbers in CP may be responsible for smaller muscle fibre size and impairment in muscle growth and contractile properties. Targeted therapies that would activate satellite cells might therefore join other efforts to design and study strategies for better management of individuals with CP. To date, however active and publicized, stem cell research has not resulted in any sound, direct therapeutic applications in CP. It has, however, taught us a great deal about many issues, from the specificity of human brain development and neuroplasticity to the challenges of discussing unproven, innovative interventions with patients and families. We have a lot yet to learn from its future developments.
Developmental medicine and child neurology