Notice Number: NOT-HL-19-679
Key Dates
Release Date : February 07, 2019
Response Date : April 15, 2019
None
Issued by
National Heart, Lung, and Blood Institute (NHLBI)
National Eye Institute (NEI)
National Institute on Aging (NIA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute on Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS )
National Center for Advancing Translational Sciences (NCATS)
Purpose
This RFI is for information and planning purposes only, and should not be construed as a solicitation or an obligation on the part of the Federal Government and participating NIH Institutes and Centers (ICs). The participating NIH ICs do not intend to make any awards based on responses to this RFI or to otherwise pay for the preparation of any information submitted or for the Government's use of such information. As part of NIH’s commitment to implementing the Regenerative Medicine Innovation Project (RMIP) established by the 21st Century Cures Act, the participating NIH ICs are soliciting input regarding in-depth cell characterization of human adult stem cells which are not of embryonic or fetal origin, including induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs). The participating NIH ICs intend to apply state-of-the-art methods and approaches to the characterization of adult stem cells and derived cell products. This information will inform future strategies for assessing the safety and effectiveness of these cell products being developed for clinical applications. Toward this end, the participating NIH ICs are seeking input on which cell characteristics should be analyzed and the optimal methods/technologies for conducting these analyses. The information obtained from the in-depth characterization will help advance the field of regenerative medicine in numerous ways, including enhancing our scientific and clinical understanding of:
- The molecular and functional properties of adult stem cells and their derivative cells
- The mechanism of action of different types of adult stem cells
- How storage, handling, isolation, ex-vivo expansion, and differentiation affects functional and biomolecular properties of adult stem cells and their derivative cells
- The basis of therapeutic potential of different types of adult stem cells
- Stem cell heterogeneity and its influence on functional properties of adult stem cells and their derivative cells
- Standards and protocols that foster reproducible results in the storage, handling, preparation, characterization, manufacturing, and clinical utilization of stem cells
- Adult stem cell in vivo viability and function as well as integration into, and interaction with, host tissues
- Correlation of the characteristics of adult stem cells and their derivative cells with clinical outcomes
Background
Current RM strategies focus on the delivery of therapeutic cells that restore normal structure and function as well as on leveraging and enhancing the body’s own innate healing capacity. A widely acknowledged challenge in stem cell research is that there are important cellular features that are not fully characterized beyond the quality attributes that are commonly used for assessing clinical grade products.1, 2 To address this knowledge gap and inform future avenues of scientific inquiry, the participating NIH ICs intend to analyze adult stem cells for key cell characteristics that can be correlated to the cells biological function, potency, and clinical efficacy. The participating NIH ICs will use the information submitted in response to this RFI at their discretion.
References
1. Regenerative Medicine Innovation Workshop December 6-7, 2017
2. Exploring Sources of Variability Related to the Clinical Translation of Regenerative Engineering Products: A Workshop October 18, 2018
Information Requested
As part of its ongoing efforts to advance the field of RM, NIH RMIP will support in-depth cell characterization of human adult stem cell products (from non-embryonic or non-fetal sources but including iPSCs and MSCs) that have been developed for clinical application. The results of the in-depth cell characterization assays performed will be shared with the scientific community to increase understanding of adult stem cell and derived cell product characteristics and how they may predict clinical outcomes and safety. Toward this end, the participating NIH ICs seek input from the biomedical research community, small businesses, and other interested organizations and stakeholders on the best approaches to molecularly and functionally characterize adult stem cells used for clinical applications.
Participating NIH ICs seek comments on any or all of the following topics (where applicable, please include pertinent references and/or names of key experts):
- The cellular features (e.g. structural/morphological, functional, omics) that should be analyzed from representative samples of source stem cells, any intermediate stage material, and final clinical-grade cell products
- Reasoning for each recommended analysis being informative (e.g. markers of: function, potency, safety, product identity, product purity; and biomarkers of clinical efficacy)
- For specific types of stem cell differentiated products (e.g. epithelial layer implants, bone marrow grafts, neuronal cell infusions, iPSC-derived cell products), the molecular or functional analyses that would be most informative and why
- The specific cell surface markers that would adequately identify cell types studied
- The specific cell characteristics that would inform assessment of the safety of stem cell-based products (e.g. markers of tumorigenicity and differentiation fidelity as well as markers associated with ectopic/unintended differentiation)
- The cellular characteristics of stem cells and their differentiated products that are informative of heterogeneity in stem cell preparations due to factors such as donor, tissue source, manufacturing conditions (e.g. isolation, expansion, differentiation, incubation period, cryopreservation, and others) as well as shipping and handling conditions
- Optimal approaches/technologies/methods for characterization of the cellular features of iPSCs, MSCs, and other adult stem cells predictive of their capacity to generate specific mature cell types, including the strengths and limitations of specific approaches and any practical considerations around sample availability, numbers, and data mining
- The potential utility of single cell assessments to determine viability and the molecular profile (i.e. determining heterogenicity of the cellular population) and its correlation to the clinical outcome
How to Submit a Response
All responses to the RFI must be submitted via email to Joel Islam (aminul.islam@nih.gov) by April 15, 2019. Please include the Notice Number, NOT-HL-19-679, in the subject line.
Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIH staff, and individual feedback will not be provided to any responder. The Government will use the information submitted in response to this RFI at its discretion. The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.
This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this RFI or from the Government’s use of such information.
The participating NIH ICs look forward to your input and we hope that you will share this RFI document with your colleagues.
Inquiries
Please direct all inquiries to:
Joel Islam, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-1651
Email: aminul.islam@nih.gov
and Human Services (HHS)
