Abstract
At present there are no clinical therapies that can repair traumatic brain injury, spinal cord injury or degenerative brain disease. While redundancy and rewiring of surviving circuits can recover some lost function, the brain and spinal column lack sufficient endogenous stem cells to replace lost neurons or their supporting glia. In contrast, pre-clinical studies have demonstrated that exogenous transplants can have remarkable efficacy for brain repair in animal models. Mesenchymal stromal cells (MSCs) can provide paracrine factors that repair damage caused by ischemic injury, and oligodendrocyte progenitor cell (OPC) grafts give dramatic functional recovery from spinal cord injury. These studies have progressed to clinical trials, including human embryonic stem cell (hESC)-derived OPCs for spinal cord repair. However, ESC-derived allografts are less than optimal, and we need to identify a more appropriate donor graft population. The cell reprogramming field has developed the ability to trans-differentiate somatic cells into distinct cell types, a technology that has the potential to generate autologous neurons and glia which address the histocompatibility concerns of allografts and the tumorigenicity concerns of ESC-derived grafts. Further clarifying how cell reprogramming works may lead to more efficient direct reprogram approaches, and possibly in vivo reprogramming, in order to promote brain and spinal cord repair.
Highlights
The focal problem for traumatic brain and spinal column injury, or neuro-degenerative disease, is that the CNS, unlike all other epithelial tissues, does not self-repair
This review will briefly summarize the preclinical studies on myelin cell transplants which led to the first clinical trials for stem cell based therapy, examine the status of cell reprogramming in order to generate autologous cells for brain repair
The pre-graft tissue preparation proved challenging indicating that the grafts need to be optimized and standardized, and the results revealed the need for a reliable index of how many grafted cells are necessary for functional improvement [21,22]
Summary
The focal problem for traumatic brain and spinal column injury, or neuro-degenerative disease, is that the CNS, unlike all other epithelial tissues, does not self-repair. The MS lesion repair is illuminating, as partial remyelination correlates with transient improvement of clinical symptoms in relapse-remitting MS This endogenous repair is overpowered by the disease process [2,3,4]. These observations suggest that functional repair may be possible if we could enhance the stem/progenitor cell pool at the injury site. This has proven true using cell transplants (exogenous repair) in many preclinical models of genetic, chemical and traumatic injury, and this opens the door for clinical transplants. This review will briefly summarize the preclinical studies on myelin cell transplants which led to the first clinical trials for stem cell based therapy, examine the status of cell reprogramming in order to generate autologous cells for brain repair
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