- Why am I asked to provide rationale for using hESC lines?
- What type of information should I provide to justify the benefits of this research to society?
- Do you have an example of what type of information I should provide in the “Abstract”?
Why am I asked to provide rationale for using hESC lines?
One charge of ESCRO is to gain public trust. The application asks for rationale so that PIs provide information to address potential public concern. The information below should be included in your response:
- Explain why other approaches have weaknesses and how your proposed method avoids or mitigates against these problems. For example, one response might be that hESCs are much less likely to be mutated.
- Describe the advantages/disadvantages of using hESC for this project compared to other types of cells, for example, adult stem cells.
- Cite and describe supporting data and research in peer-reviewed scientific journals. If there are valid alternatives to using hESC to answer research questions, please briefly describe why these alternatives are not being used.
What type of information should I provide to justify the benefits of this research to society?
Describe how the potential benefits should outweigh the potential impacts and risks. Explain how the research is intended to advance science and medical knowledge and/or benefit human health.
Abstract: (describe in 250 words or less, in layman’s terms, the goals of the research, rationale for using hESC lines, brief description of the approach, and benefits to society)
Goals: To assess the efficacy of newly generated hESC lines by investigating the fate of hES cells that were 1) injected into various sites within the adult mouse, to test their ability to generate teratomas, e.g., sub-cutaneous, intramuscular, kidney capsules and testes, or 2) injected into a mouse embryo to generate xeno-chimeras, to test their normal development up to mouse embryonic day 11.5.
Rationale & Benefit: Teratoma formation is the only assay we currently have to assess the array of tissues that can be formed from a particular hESC line. Given that these tissues are tumors, growth is disorganized and difficult to relate to normal development. Contribution to chimeras provides a context to the development. If a cell is present within a particular tissue, development is considered normal and the starting hESC lines would be thought to have the capability of forming that tissue. hESC lines have different abilities following directed in vitro differentiation. There are as many protocols for directed differentiation as there are investigators and target tissues. Development within the in vivo context of a chimera could potentially allow us to assess the ability of any particular line more accurately than either in vitro assays or teratoma formation. We will start this project using non-human primate ES cell lines, with the plan that if the primate-cell assays work well, and once ESCRO approval is given, we will proceed to assess all human ES cell lines in this fashion.
Methods: Direct injection of undifferentiated and differentiated hESCs and iPSCs into tissues in question.