We produce neurons by genetic engineering of somatic cells, typically commercially available dermal fibroblasts. These fibroblasts are often derived from perinatal foreskins or young donors which are relatively easy to convert into neurons, however, dermal adult fibroblasts from much older donors can also be reprogrammed into neurons. We have been able to reprogram skin fibroblasts obtained from 3mm-wide skin punch biopsies of a 58 years-old donor. This means that in the future, we could produce autologous neurons from any human donor.
Our technology has three advantages:
- We have developed a formulation of cryoprotectants to preserve skin punch biopsies 3mm in diameter into dry ice for long distance shipping. Outpatient biopsies are convenient for donors with reduced mobility. Following this procedure, frozen dermal tissues successfully produced fibroblasts that were reprogrammed into neurons.
- Our reprogramming procedure is direct from somatic cells, without pluripotent cell intermediates. This removes the risks of teratoma formation in implanted neurons derived from pluripotent stem cells.
- Our procedures do not involve expression vectors or transgenes. In absence of exogenous sequences and without any possibility of insertional mutagenesis, the risk of tumor formation upon reimplantation of autologous neurons is reduced compared to other methods.
Neurons generated by these procedures should be clean of any residual exogenous sequences and insertional mutations. During transplantation trials in laboratory animals that are immunodeficient like nude mice, these neurons should produce a lower rate of tumor or teratoma formation than those produced by other methods. This makes these induced neurons interesting candidates for future autologous implants in patients in advanced stages of neurodegeneration. Besides therapeutic applications, we may speculate on the effects of a few extra million neurons implanted in the brain of a human host that already contains ~80 billion neurons. We could reasonably predict that implanted autologous neurons should integrate the neural network of the host, producing improved neural plasticity and new synaptic connections for learning new tasks. Perhaps autologous neurons implants will become a commodity for the aging populations of the future. An example of neural reprogramming is shown below, starting with skin fibroblasts (left), these cells are slowly reprogrammed into neurons (right).
