- Autologous iPSC-derived neural progenitors survive in the monkey brain for 6 months
- Grafted cells differentiate into neurons, astrocytes, and oligodendrocytes
- Autologous transplantation elicits minimal immune and glial response
The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.
Here’s the short short version: researchers took a skin biopsy of three Rhesus monkeys, treated it with a retrovirus to revert it back to a stem cell state, and then were differentiated into a 50/50 split of neurons and pre-neural cells. They were then put back into the original monkeys from which they were removed (that’s the “autologous” part … it’s a trick to prevent autoimmune response). After about 6 months, there was no trace of stem cells (meaning they all differentiated at this point), but their conditions didn’t improve much. This was likely due to the ratio of cell differentiation, since all of the other aspects of the transplant went very well.
Despite small graft size, the grafted neurons do project axons over a long distance even under the adult brain environment, oligodendrocytes produce myelin sheaths, and glial response is minimal. The scarcity of dopamine neurons in the grafts and lack of functional improvement in the animals are likely due to the neural differentiation strategy that does not yield sufficient numbers of midbrain dopamine neurons besides the reasons described above. Recently, we (Xi et al., 2012 ), as well as others (Kriks et al., 2011 ; Kirkeby et al., 2012 ), have developed an efficient strategy for differentiating primate ESCs and iPSCs to authentic midbrain dopamine neurons, which will allow us to evaluate individualized cell therapy in the primate model at the functional level for a longer term.
As proof of concept, the tests went well. Now they have to fine-tune the proportions of cell types, and they may see some improvement of symptoms. This kind of research shows promise in eventually being able to treat humans with degenerative brain disease.