Good news!
"Researchers have successfully developed nerve grafts, currently being trialed as a treatment for Parkinson’s disease, that are invisible to the body’s immune system, according to a new study. It could mean risky post-transplant anti-rejection drugs are soon a thing of the past. ...
In stem-cell-derived neural grafting, human pluripotent stem cells (hPSCs), adult cells such as skin cells reprogrammed to act like stem cells again, are guided to develop into dopamine-producing (dopaminergic) neurons. These are the kinds of neurons that are destroyed in Parkinson’s disease. The dopaminergic neurons are grown in a lab and then transplanted into the brain. ...
For the present study, the researchers engineered hPSCs to “overexpress 8 immunomodulatory transgenes.” ... Overexpression just means making lots of something. "Immunomodulatory' is something that calms or adjusts the immune system. And transgenes are genes scientists have inserted into a cell that weren’t there originally. ...
This is the next generation of neurological treatment, and it could be used as a safe, off-the-shelf product suitable for treating diseases for which cell-based therapies are a viable option, such as stroke, Huntington’s disease, heart disease and diabetes.” ..."
"... Neural grafts are a realistic future treatment for many neurological disorders and for Parkinson’s disease patients this is coming close to reality, with at least 3 major clinical trials in progress. ...
said the neurons also had an ‘off’ switch [suicide gene?] so that they can be activated if desired, to eliminate the risk of tumours developing from grafts. ..."
From the highlights and abstract:
"Highlights
• Cloaked human neural grafts evade immune detection in humanized mouse model
• Cloaked human neural grafts reverse motor symptoms in Parkinsonian rats
• Suicide gene incorporation into cloaked donor stem cells ensures safety
Summary
Human pluripotent stem cell (hPSC)-derived therapies are a realistic possibility for numerous disorders, including Parkinson’s disease.
While generating replacement neurons is achievable, immunosuppressive drug challenges, to prevent rejection, remain.
Here we adopted a hPSC line (termed H1-FS-8IM), engineered to overexpress 8 immunomodulatory transgenes, to enable transplant immune evasion.
In co-cultures, H1-FS-8IM PSC-derived midbrain neurons evaded rejection by T lymphocytes, natural killer cells, macrophages, and dendritic cells.
In humanized mice, allogeneic H1-FS-8IM neural grafts evaded rejection, while control hPSC-derived neural grafts evoked activation of human immune cells, elevated inflammatory cytokines in blood and cerebrospinal fluid, and caused spleen and lymph node enlargement.
H1-FS-8IM neural grafts retained functionality, reversing motor deficits in Parkinsonian rats.
Additional incorporation of a suicide gene into the H1-FS-8IM hPSC line enabled proliferative cell elimination within grafts. Findings demonstrate feasibility of generating a population-wide applicable, safe, off-the-shelf cell product, suitable for treating diseases for which cell-based therapies are a viable option."
Parkinson’s disease researchers develop cellular ‘invisibility cloak’ to protect neural grafts (original news release)
Graphical abstract
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