Scientific Retreats 2012

April 23, 2012

Session Topic: iPSC Opportunities in NIAMS Diseases


Pluripotent stem cells (SCs) have infinite self-renewal capacity and can differentiate into adult specialized cells of all types, properties that make them useful for a variety of biomedical applications. The recent demonstration that differentiated cells, such as fibroblasts, can be reprogrammed into induced pluripotent stem cells (iPSCs) has made it relatively easy to generate patient-specific pluripotent SCs. This discovery overcomes many of the limitations of embryonic stem cells (ESCs), and has therefore opened up new approaches to the study and treatment of human disease. Research over the last few years has been largely focused on developing efficient protocols for the generation of iPSCs, characterization of the resulting iPSCs, and development of protocols to differentiate iPSCs into specialized cell types.

The use of iPSCs in tissue engineering and regenerative medicine (TE/RM) may be an area of great potential for the development of personalized medicine approaches in NIAMS diseases. An iPSC-based therapeutic approach has the advantage that specialized cells derived from patient-specific iPSCs would be expected to be recognized as self by the immune system, thereby avoiding immune rejection. Cell replacement therapy could be possible even when the patient no longer has a sufficiently large endogenous tissue-specific stem cell population. In the case of monogenic diseases, it is theoretically possible to correct the genetic defect prior to differentiating iPSCs into specialized cell types used for therapy. The unlimited proliferative potential of iPSCs facilitates this gene correction step. Cell-based therapies using patient-derived iPSCs require the ability to 1) make iPSCs from patient cells (e.g., skin or blood), 2) efficiently differentiate these cells into the specialized adult cell type needed for therapy, and 3) purify these cells away from the pluripotent iPSCs that would form teratomas when introduced back into the patient.

Mouse models have been used extensively for studies on disease pathogenesis and for pre-clinical drug testing. However, it is difficult to engineer a mouse model for a polygenic disease. In addition, mouse models are not amenable to high-throughput drug screening, and many therapies that work in mice are ineffective in humans. As an alternative approach, iPSCs can be generated from patients with specific conditions or disease states, and then differentiated to the relevant cell type to be used to create an in vitro model for that disease or condition. Individualized in vitro cell-based models could be used to study disease pathogenesis and for preclinical screening of drug candidates. iPSCs offer multiple advantages over primary cells. For example, their unlimited proliferative potential allows researchers to culture the numbers of cells necessary for high-throughput screening, delivery of large numbers of therapeutic cells, and other applications. Patient-specific cellular models of polygenic disease may also be useful to interrogate molecular and cellular effects of genetic variations that are associated with disease pathogenesis, as well as drug efficacy and toxicity. Cellular and molecular phenotype data (e.g., mRNA and miRNA transcriptomics, epigenomics, metabolomics, proteomics) derived from these models could also be combined with genotype and clinical phenotype data to add a functional dimension to genomic studies.

The Purpose of the Session/ Goals

Participants will discuss recent advances in iPSC technology, as well as potential applications of iPSCs within the NIAMS mission areas. We will also discuss opportunities for NIAMS extramural programs to leverage resources and expertise being developed by the NIH Common Fund (e.g. the NIH Center for Regenerative Medicine (NIH CRM)) and by other institutes.

Issues to be Addressed/ Key Questions

  • What NIAMS diseases/conditions and research areas are poised to take advantage of recent advances in iPSC technologies, and would adoption of iPSC approaches accelerate progress? What are the current limitations in the use of iPSCs for these applications?
  • Are there appropriate in vitro cellular models for common and rare diseases of interest to NIAMS that could be generated from patient-specific iPSCs?
  • Are any of these models ready for 1) studies of disease pathogenesis, 2) functional studies of gene variants, 3) high-throughput drug screening, 4) drug toxicity studies, and 5) studies of gene repair?
  • What are the technological hurdles, and are special resources required to overcome them?
  • What are the opportunities for leveraging and partnerships?


Tiscornia G, Vivas EL, Belmonte JC. Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med. 2011 Dec;17(12):1570-6.

Grskovic M, Javaherian A, Strulovici B, Daley GQ. Induced pluripotent stem cells--opportunities for disease modeling and drug discovery. Nat Rev Drug Discov. 2011 Nov 11;10(12):915-29.