Clinical Trial: Feasibility of Generating Pluripotent Stem Cells From Patients With Familial Retinoblastoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Feasibility, Validation and Differentiation of Induced Pluripotent Stem Cells Produced From Patients With Heritable Retinoblastoma

Brief Summary:

The goal of this study is to determine if human RB1-deficient induced pluripotent stem cells (iPSCs) can produce retina, and, furthermore, can give rise to retinoblastoma in culture. This unique opportunity to study the initiation of retinoblastoma in the developing retina will shed light on the cell of origin for retinoblastoma and allow the investigators to study the earliest molecular and cellular events in retinoblastoma tumorigenesis.

OBJECTIVES:

  • To establish the feasibility of producing induced pluripotent stem cells (iPSCs) from retinoblastoma patients with germline RB1 mutations (RB1-deficient iPSCs).
  • To validate human RB1-deficient iPSCs by confirming karyotype, pluripotency and RB1 mutation.
  • To differentiate the RB1-deficient iPSCs into retina as a model of the initiation of retinoblastoma in the developing retina.

Detailed Summary: This is an observational study where a small skin cell sample or peripheral blood sample will be used to produce iPSCs. After RB1-deficient iPSCs are produced, their karyotype and RB1 mutation will be confirmed and their pluripotency will be tested by studying the expression of pluripotent genes and proteins according to standardized guidelines established for human iPSCs. After validation of the RB1-deficient iPSCs, they will be differentiated in the laboratory into retina following established protocols.
Sponsor: St. Jude Children's Research Hospital

Current Primary Outcome: Number of samples which successfully produced iPSCs [ Time Frame: Once at enrollment ]

Skin biopsy or peripheral blood mononuclear cells will be collected from eligible, consenting participants and shipped directly to the University of Wisconsin for processing. All samples will be returned to the St. Jude investigator within two months of reprogramming for further analysis.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of samples with validated RB1-deficient iPSCs [ Time Frame: Once at enrollment ]
    Samples will be analyzed for standard G band karyotype and FISH analysis (RB1 probe), targeted RB1 mutation (based on known mutation of patient from whom the sample was derived), and validation of pluripotency based on standard protocols.
  • Number of samples that differentiate human iPSCs toward an eye field fate [ Time Frame: Once at enrollment ]
    The best available methodology will be utilized for analyses of the RB1-deficient iPSCs.


Original Secondary Outcome: Same as current

Information By: St. Jude Children's Research Hospital

Dates:
Date Received: July 16, 2014
Date Started: November 4, 2014
Date Completion: April 30, 2018
Last Updated: May 15, 2017
Last Verified: May 2017