Starting Out on the Long Road to Tissue Engineering for the Brain

Can one replace parts of the brain? In principle, yes. It is a tissue, and tissue engineering is a field intent on regrowth and replacement of lost or damaged tissue. There are parts of the brain immediately vital to life, and parts that hold the memory that defines the self; if those are lost, that is irrecoverable. But much of the brain might be tissue engineered in the same way as muscle or liver might be replaced. Researchers are still in the early stages of the long road towards replacement tissues created to order, as illustrated by the scientific work noted here, but much of the brain will be a part of that field of development.

The transplantation of pluripotent stem cell-derived neural precursors into the cortex is an exciting potential approach to repair the brain. To achieve this goal, grafted cells must re-establish damaged neural circuits that participate in the restoration of lost behavioral function. Significant progress has been made in demonstrating the feasibility of transplanting precursor cells to replace neurons in the cortex. Graft-derived neurons can survive for years in mice and differentiate into appropriate neuronal subtypes that exhibit normal electrophysiological activity, project long distances outside of the graft to appropriate targets, synaptically integrate with surrounding host neurons, and respond to sensory input and participate in motor output.

Despite these significant discoveries, it is unclear whether grafted neurons in the neocortex can encode useful behavior as a result of their electrophysiological activity. Reported behavioral benefits are instead a result of activity-independent functions such as the secretion of anti-inflammatory or neurotrophic factors. The inability to demonstrate that electrophysiological activity of grafted neurons encode useful behavior is not surprising considering there are cortical cell types that are thus far missing in grafts, in addition to these grafts lacking normal cortical cytoarchitecture. While cerebral organoids display a subset of similar characteristics to a normal fetal cortex, their differentiation has thus far been abnormal after transplantation. Therefore, there is currently no method of generating facsimiles of neocortical tissue in adults, whether for the purpose of study or therapy.

The goal of this study is to provide an initial proof of concept for a neocortical grafting platform that supports (1) the survival and differentiation of the major neocortical cell types, (2) vascularization, (3) neuronal integration, and (4) layering. Toward this goal, we tested whether grafting cells in a three-dimensional scaffold could sustain the differentiation of all the major cortical cell types, vascularization, and a layered cytoarchitecture. Using dissociated mouse cortical fetal cells mixed with a commercial scaffold, we found that the neuronal, glial, and vascular components within the graft survived and successfully integrated with the host tissue. Our results suggest that this platform is suitable for future optimization and testing of structured, vascularized, multi-cell type neocortical tissue prototypes.



The brain consists of lots of supporting tissues which if kept . There are some non-cortex areas which might be repairable at 100% of capacity can help maintaining the actual neurons for at least 100 years (we have supercentenarians who are in their mind).

As for the (neo) cortex tissue repair ... hile this is an extremely interesting subject its value for the next couple of decades will lie rather on the philosophical plane. We have very poor understanding of mind/"self"/intelligence or even creativity. If we look at the generative AI , i am left in the dust on creativity and art and essay writing, for example. It is very plausible that some trait-defining features of the human personality can be tweaked with small hormone influences like being more/less aggressive and lazier, more alert/more impulsive. A few small changes can add-up over 10 years to a completely different personality. Without any profound meddling. Interestingly, a huge chunk of our perception of "self" is the professional knowledge. That part most probably will be amenable to "uploading". Another part that defines us is what books we read and what movies we watch. And ironically a somewhat smaller portion is our actual experience and memories. For now this discussion is quite theoretical and dare i say scholastic.

Posted by: Cuberat at February 27th, 2023 9:13 AM

I'd say I could loose all my memories since I was ~35 years old (tragic as that would be) and would still be essentially the same person I am now, perhaps even happier, as events since then have contributed to an unhealthy level of cynicism.

Posted by: Thomas Schaefer at March 2nd, 2023 8:10 AM
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