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RL1-00672-1: In vitro and in vivo characterization of human neuronal precursor cells

Recommendation: Not recommended for funding

Public Abstract (provided by applicant)

There are a number of diseases that affect the brain, including Alzheimer’s disease, Parkinson’s disease, and Amyotrophic lateral sclerosis (ALS). In addition, trauma can cause neurological problems. We have developed two cell strains that are derived from human neuronal cells. These cell strains are precursors to other neuronal cells, and we have shown that the cells can differentiate when grown in cell culture. This project will determine the characteristics of these cells, including which important proteins are found in the cells, in order to better understand how the cells function. In addition, a variety of signaling molecules will be investigated to see how they affect the cell strains. These signaling molecules may affect differentiation or other functions of the cells. We will also test the cells strains in animals to determine if they may be suitable for therapy for neurological diseases. Overall, the project will determine if these cell strains will be useful for further experiments that may lead to drug or stem cell therapy.

Statement of Benefit to California (provided by applicant)

There are many Californians that have neurological problems. These problems range from injuries due to trauma, degenerative diseases such as Alzheimer’s and Parkinson’s diseases, and dementia caused by HIV and HCV. We have developed human neuronal precursor cells. Studying these cell strains will provide information that will advance the field of neurobiology. In addition, these strains or the information obtained through these studies may be useful in the future for therapies for a variety of neurological problems.

Review

This proposal examines two neural cell lines that have been established from human neuronal cells, and then maintained in cell culture using growth factors but without feeders. The cells will grow either as adherent cells or neurospheres, but their potency has not thus far been assessed. The project plan is to molecularly and functionally characterize the two cell lines in culture and upon transplantation into mice.

Well-validated neuronal stem cell lines that have the ability to form different types of human neurons in culture and in vivo would certainly be valuable to the field, but the lack of detail in this application makes it impossible to be confident that this goal would be achieved. The applicant will use two poorly-characterized cell lines to conduct a series of poorly-described and poorly-thought-out experiments. The applicant and the institution that he/she works in have little to no experience in the field and are not equipped to do the kind of research outlined here. Finally, this proposal is not responsive to the RFA in that the cell lines are not pluripotent.

Specifically, the characterization of the cells is poor and the preliminary data does not suggest that they will be useful in generating new and significant knowledge on stem cells, or likely be used in transplantation-induced repair in any human disease. No details on the proposed molecular tools are provided. The transplantation experiments are absolutely critical, but are described in so little detail that interpretation is impossible. It was unclear where the cells would be implanted, how integration and function would be assessed, or how potential tumor formation would be determined.

In conclusion, this application did not give the reviewers any confidence that the investigator understands the field well enough to generate valuable data. Their concern was heightened by the CV of the principal investigator, as his/her published experience appears to be largely in virology.

The following Working Group members had a conflict of interest with this application and were therefore recused from participating in review of, discussion of, and voting on the application:

• None