To What Degree Can Cell Therapies Rebuild the Aging Brain?

Repair of the aging brain is perhaps the most important of goals in regenerative medicine. We are the data that is stored in some way within the small-scale structures of our brain tissue, and so the options for outright replacement of brain cells and tissues are somewhat constrained. As a thought experiment, it is in principle possible, given significant progress in biotechnology, to manufacture a cloned body to receive a transplanted brain. All of the steps needed either already happen in nature, such as the growth of bodies without brains, and would need control and direction, or have been crudely demonstrated in animal studies, such as brain transplants, albeit with major limitations and risk of failure. There may well be little gain in transplanting an aged brain if it cannot be repaired, however.

In any case, my view is that major surgery involving replacement parts will not be a primary focus for the future of medicine. Instead, increasing control over cells and cell signaling will lead to rejuvenation through either restoration and repair of native cells or, where that is impractical, the delivery of youthful cells to replenish stem cell populations. It is an interesting question as how far one might be able to go with this type of approach for the aging brain. Much of the brain, while vital, is uninvolved directly in the storage of the data of the mind. It might be considered simply a less accessible and more difficult target for regeneration in comparison to other organs. It is those areas of the brain in which data is stored that present a challenge for any sort of replacement therapy, however, and it remains to be seen as how this challenge may be effectively addressed.

Pluripotent stem cell strategies for rebuilding the human brain

Age - it's the one mountain you can't overcome, and as the average life expectancy extends into the eighth decade, neurodegenerative diseases are becoming increasingly prevalent. Despite their increasing incidence, preventative or disease-modifying strategies for these emotionally and financially draining disorders are lacking. Due to the fundamental lack of regeneration within the central nervous system (CNS), neurodegenerative diseases relentlessly attacking discrete populations of neurons are excellent candidates for cell replacement therapies. Here, we review the current prospects on the application of pluripotent stem cell-derived cell types for the treatment of neurodegenerative disease.

Pluripotent stem cells provide a uniquely scalable source of functional somatic cells, including cells of the CNS, that can potentially replace damaged or diseased tissues. Although prospects for using stem cell derivatives seemed fanciful at the start of the millennium, approximately two decades later several clinical trials using cellular products of pluripotent stem cells are underway or about to reach the clinic. It's an incredibly exciting time for stem cell-based regenerative medicine with a number of clinical trials started and more just on the horizon for neurodegenerative diseases, including one for Parkinson's disease.

The demand for neurodegenerative disease therapeutics continues to grow as populations around the globe age. Currently, no pharmacological strategies exist that can significantly alter disease course for neurodegenerative diseases, thus cell replacement therapies remain an attractive avenue of exploration. Although the prospect of using stem cell-derived neurons to treat many of the diseases discussed in this review remains abstract, the Parkinson's disease clinical trials, grounded on years of fetal transplant studies and animal models with high fidelity, will provide important guideposts as others venture into these uncharted territories.