Sunday, May 15, 2022

Seeding stem cells into the brain may help cure Parkinson's motor symptoms -- it works in mice, so far

Good news!

"... Other neurodegenerative diseases could also be treated using this approach. ...
Researchers ... are homing in on a new and excitingly efficient cure against the motor symptoms of Parkinson’s disease. While promising, their results so far have only been obtained from lab rats.
Parkinson’s disease is a neurodegenerative disease that affects over 10 million people worldwide. ...
These motor impairments, according to the team, can be reversed using stem-cell-derived neural grafts — at least in the brains of mice. ...
the study, the team cultured iPSCs for 17, 24, and 37 days. While all batches successfully transformed into the desired type of neurons, those cultured for 17 days proved themselves to be the best at the task. The neurons that developed from this batch survived for longer and in greater numbers than the rest, and grew longer axons and dendrites. ...
Rats who received grafts made with the 17-day iPSCs showed ‘remarkable’ recovery from the motor symptoms of Parkinson’s, although this effect was dose-dependent. Animals who only received a small number of cells showed minimal improvements, but those who received larger grafts showed more developed neural branching and complete reversal of the symptoms. ..."

From the abstract:
"In pursuit of treating Parkinson’s disease with cell replacement therapy, differentiated induced pluripotent stem cells (iPSC) are an ideal source of midbrain dopaminergic (mDA) cells. We previously established a protocol for differentiating iPSC-derived post-mitotic mDA neurons capable of reversing 6-hydroxydopamine-induced hemiparkinsonism in rats. In the present study, we transitioned the iPSC starting material and defined an adapted differentiation protocol for further translation into a clinical cell transplantation therapy. We examined the effects of cellular maturity on survival and efficacy of the transplants by engrafting mDA progenitors (cryopreserved at 17 days of differentiation, D17), immature neurons (D24), and post-mitotic neurons (D37) into immunocompromised hemiparkinsonian rats. We found that D17 progenitors were markedly superior to immature D24 or mature D37 neurons in terms of survival, fiber outgrowth and effects on motor deficits. Intranigral engraftment to the ventral midbrain demonstrated that D17 cells had a greater capacity than D24 cells to innervate over long distance to forebrain structures, including the striatum. When D17 cells were assessed across a wide dose range (7,500-450,000 injected cells per striatum), there was a clear dose response with regards to numbers of surviving neurons, innervation, and functional recovery. Importantly, although these grafts were derived from iPSCs, we did not observe teratoma formation or significant outgrowth of other cells in any animal. These data support the concept that human iPSC-derived D17 mDA progenitors are suitable for clinical development with the aim of transplantation trials in patients with Parkinson’s disease."

Seeding stem cells into the brain may help cure Parkinson's motor symptoms -- it works in mice, so far

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