Acceptability of neural stem cell therapy for cerebral palsy: survey of the Australian cerebral palsy community

Background Neural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions. The aim of this study was to determine the acceptability of NSC therapy for CP in the CP community. Methods Australian residents with CP and parents/carers of those with CP completed a questionnaire to determine their willingness to use NSCs from three sources (fetal, embryonic and induced pluripotent stem cells) and their willingness to undergo accompanying procedures (neurosurgery, immunosuppression) that carry potential risks. To further explore their views, participants also answered free text questions about their ethical concerns regarding the source of NSCs and their perceptions of meaningful outcomes following NSC treatment. Results In total, 232 responses were analyzed. Participants were willing to use NSCs from all three cell sources and were willing to undergo NSC therapy despite the need for neurosurgery and immunosuppression. Participants identified a range of outcome domains considered important following NSC treatment including gross motor function, quality of life, independence and cognitive function. Conclusions Hypothetical NSC therapy was acceptable to the Australian CP community. This study has identified important findings from the CP community which can be used to inform future NSC research, including the design of clinical trials which may help to increase recruitment, compliance and participant satisfaction. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-023-03246-2.

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Are there any benefits associated with being in the study?
This survey aims to gather your opinions about neural stem cells, which could inform our future research and could help ensure stem cell therapies are relevant to people in the cerebral palsy community. We do not expect the results of this survey to have any direct or immediate benefit to the participants.
What will happen to information about me that is collected during the study?
All information gathered in this survey is confidential and can only be accessed by Madeleine Smith and Dr Madison Paton. All data gathered will be stored securely via the cloud on the University of Sydney's version of REDCap. Study findings may be published, presented at scientific conferences and written up in Madeleine Smith's PhD thesis, but you will not be individually identifiable. You will have access to the results of this survey at the study's completion, via a report emailed to you once this study is finished.
What if I have a complaint or any concerns about this study?
Research involving humans in Australia is reviewed by an independent group of people call a Human Research Ethic Committee (HREC). The ethical aspects of this study have been approved by the HREC of the University of Sydney (protocol number: 2020/495). As part of this process, we have agreed to carry out the study according to the National Statement on Ethical Conduct in Human Research (2007). This statement has been developed to protect people who agree to take part in research studies.
If you are concerned about the way this study is being conducted or you wish to make a complaint to someone independent from this study, please contact the university using the outlined details below. Please quote the study title and protocol number.

Survey welcome
Thank you for agreeing to participate in our research survey: Your opinion: Neural Stem Cell Therapy for Cerebral Palsy The following questions will ask for some contact details and some information about you. You will now be presented with some information on stem cells

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Cells are the building blocks for every part of our body, which are formed from stem cells.
Stem cells are able to develop into specialised cell types in the body. In most countries stem cells are only used to treat blood cancers, for skin grafting and some autoimmune diseases.
There is yet to be a proven stem cell treatment for cerebral palsy, but different stem cell types are currently being researched. There are currently more than 10 human research trials, known as clinical trials, underway internationally using stem cells to treat cerebral palsy.
14) We want to know your opinion prior to giving you more 0 -Totally unacceptable information about stem cells. You will now be presented with some information on neural stem cells There are many different types of stem cells. This survey is focusing on one type, neural stem cells, which can turn into the main cell types of the brain. Neural stem cells can reduce the damage caused by brain injury and therefore, can potentially reduce the severity of cerebral palsy.
There have been many animal studies conducted around the world showing that neural stem cells can be beneficial following brain injury. Additionally, neural stem cells have been tested in clinical trials as a potential treatmeant for disorders of the central nervous system such as stroke, Parkinson's disease and spinal cord injury. Therefore, neural stem cells could possibly be used to treat people diagnosed with cerebral palsy.
The following table below outlines examples of scientific outcomes following studies using infant animal models.
Page 9 16) The next section will ask your opinion on neural stem cell therapy, please ensure that you have read and understood the above.

How do we obtain neural stem cells?
Neural stem cells get their name 'neural' because they come from the brain. We, therefore, need to obtain these cells from brain tissue or produce brain cells from other cell types in the laboratory.
You will now be presented with information on three different sources of neural stem cells to understand whether you find each cell type acceptable.

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Neural stem cells can be sourced from fetal tissue. In this case, they are obtained from brain tissue of electively aborted fetuses with consent and as a donation to medical research. The neural stem cells are then isolated and grown in the laboratory, ready to use for research.
Would you be willing to use fetally-derived neural 0-Not willing to use stem cells to treat cerebral palsy in yourself/your 1 child? 2 3 4 5 -Unsure 6 7 8 9 10 -Very willing to use Furthermore, neural stem cells can be formed from embryos. They are sourced from embryos that are either unsuitable for IVF or are no longer required by the patient and are donated to medical research, with consent. Embyronic stem cells are obtained from the inner cell mass of the blastocyst (seen below). In normal development these cells would subsequently turn into all cells of the body, for example muscle and bone cells. When scientists extract these cells from the inner cell mass, they maintain their embryonic stem cell characteristics in the laboratory. These embryonic stem cells then require some laboratory manipulation to form neural stem cells.
Would you be willing to use embryonically derived 0-Not willing to use neural stem cells to treat cerebral palsy in 1 yourself/your child? 2 3 4 5 -Unsure 6 7 8 9 10 -Very willing to use Adult cells can be engineered in the laboratory to form neural stem cells. These cells are not derived from the brain, they can be sourced from cells such as skin cells. These cells are called induced pluripotent stem (iPS) cells. An example of this process would be forming neural stem cells from adult skin cells (fibroblast cells).
Would you be willing to use neural stem cells derived 0-Not willing to use from induced pluripotent stem cells to treat cerebral 1 palsy in yourself/your child? 2 3 4 5 -Unsure 6 7 8 9 10 -Very willing to use

Availability of neural stem cells for research and clinical trials
Fetally-derived neural stem cells are ready to be used in human research trials, known as clinical trials. Some may consider these cells to be ethically controversial, since they are derived from fetal tissue.
In contrast, induced pluripotent stem cells are derived from adult cells, but are not yet available for human clinical trials. Induced pluripotent stem cell are not ready to use in humans because further research is required to determine their safety and effectiveness. This is summarised in the How do we give neural stem cells to patients?
Stem cells could be administered into the body to treat brain injury via: -Intravenous infusion: stem cells delivered into the blood circulation via a drip -Direct injection to the site injury: requires neurosurgery so stem cells can be directly injected to the site of injury, where they are needed Scientists have considered both methods listed above to give neural stem cells. It is more likely that direct injection of neural stem cells into the brain would be the most effective way to deliver neural stem cells. This would involve neurosurgical injection of neural stem cells by a neurosurgeon under general anaesthetic (deep sleep during surgery).
Neural stem cells are different from other stem cell types, because to be most effective, they cannot be given via a drip. If a drip was used to deliver neural stem cells, they cannot travel effectively to the brain, which is were we want the cells to do their work in the brain and rebuild tissue.
You will now be presented with a table that 'weighs up' the benefits and risks/considerations of neurosurgical administration of neural stem cells.