Stem Cells for improving the treatment of neurodevelopmental disorders

Unfortunately I cannot find the full document.


So stem cells work for autism?

Maybe. I donā€™t think it is settled, but I found this:

Eight subjects showed decreased CARS and ATEC scores over the course of treatment, to the point of changing symptom categories in their respective scales. The scores of three participants of this group, remarkably, changed from the category of severe autism to below the autism threshold on the CARS when the 12ā€month visit was compared with baseline.

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Very interesting!
I wonder which company is trust worthy to provide good stem cell supportā€¦
I also want to know how much a session and how many sessions it takes
And I also want to know for how long would I have to take them Im order to revive results
It would be to manage my social complexes which lead to agro behavior
And also to manage my obsessive behavior that result in anxiety and depression.
Thank yiu

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The autism study was in 20 kids, 8 of which had the notable results, and three had really spectacular results. The kids were an average age of 10, and had 4 intravenous infusions over a period of 9 months.

As far as I know, no one is doing this in schizophrenia yet and any ā€œstem cell clinicsā€ that are would be offering something unapproved and possibly dangerous (mostly because who knows what theyā€™re giving you.)

You can always try using SCI-HUB to download the full document.

It doesnā€™t appear to be there yet.

Itā€™s on scihub!

Selected quotes:

Early studies in this field demonstrated the remarkable ability for MGE interneurons to survive and migrate[131] and enhance inhibition[132] when transplanted into an adult brain. Therefore, the first proofā€ofā€concept studies transplanted fetal MGE tissue into the ventral hippocampus of rodent models of schizophrenia. Using the methylazoxymethanol (MAM) model of schizophrenia, Perez et al demonstrated that MGE transplants into the ventral hippocampus reduce pyramidal cell firing rate in the vHipp. Further, these cells also normalize firing of dopamine cells in the downstream ventral tegmental area (VTA) and reduced amphetamineā€induced locomotor activity, a behavioral test that is used as a correlate of positive symptoms[133]. Similarly, in a genetic model of hippocampal disinhibition, the Cyclin D2 knockout mouse (ccnd 2 ā€/ā€), MGE transplants were also able to normalize hippocampal activity and dopamine cell activity in the VTA. Further, amphetamineā€induced locomotor activity was also normalized by MGE transplants in this model. Interestingly, Gilani et al also found that MGE transplants improve contextual fear conditioning, one type of hippocampalā€dependent cognitive function that is disrupted in SZ[134]. The primary interneuron subtypes that have been implicated in schizophrenia are parvalbuminā€ and somatostatin positive cells[135] and these experiments found that the majority (56%) of transplanted MGE cells mature into PVā€positive interneurons while about 35% become SSTā€positive interneurons[136]. To better understand the role of these specific interneuron subtypes, more recent work has used a dualā€reporter mouse embryonic stem cell line to grown enriched populations of PVā€ or SSTā€positive interneurons. These cells were transplanted into the vHipp of the MAM model of schizophrenia. Both PVā€ and SSTā€positive interneurons were able to decrease firing rate and increased sIPSC amplitudes in vHipp pyramidal cells. Further, both cell types reduced hyperactivity in the dopamine system and attenuated deficits in dopamineā€dependent cognitive function[137].

While stem cells hold the potential to help us understand and better treat neurodevelopmental disorders like schizophrenia and autism, multiple questions remain. The first is the validity of 2D or 3D cultures for understanding complex disorders that involve multiple cell types and circuits. Both schizophrenia and autism have been associated with dysfunction of the immune system and to date, stem cell models do not include the primary immune cells of the brain, microglia. Further, epigenetic mechanisms, or nonā€permanent alterations to the 3D structure of DNA that causes changes in gene expression, have been implicated in both schizophrenia[149] and autism[150]. The process of reprogramming somatic cells can erase the epigenetic signature. However, newer processes reprogramming, called transdifferentiation, may be able to get around this problem

As stem cells move into the clinic as potential therapies, multiple issues will need to be addressed. First and foremost, extensive testing will be required to determine the safety of cell transplants and the duration of their effect. Although MSCs for the treatment of autism have already begun to make their way into the clinic, multiple questions still exist related to this highly controversial cellā€based therapy[154]. First, MSCs are an extremely heterogeneous population of cells with no specific cell markers[155]. In addition, without targeted delivery, it is impossible to ensure that the cells will reach the target site, especially in the case of autism where there is no overt tissue injury[155]. Further, little is known about the behavior of these cells in vivo, specifically the immunologic properties of the cells. Finally, although MSCs are thought to have their beneficial effects through their ability to suppress immune signaling, promote neurogenesis and plasticity, and to release neurotrophic factors, their mechanism has not been completely elucidated. In addition, highly standardized and efficient protocols for growing stem cells will need to be developed. In the case of using interneurons, for example, techniques for generating a highly pure population will be necessary to prevent the possibility of tumorigenesis. Further, the process or growing human interneurons in vitro is currently in line with the time course of human development, suggesting that more efficient protocols need to be developed.

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