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Directed Differentiation of Induced Pluripotent Stem Cells towards T Lymphocytes
Published on: May 14, 2012
Immunogenicity of induced pluripotent stem cells
Tongbiao Zhao1, Zhen-Ning Zhang, Zhili Rong
1Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0322, USA.
Nature
|May 17, 2011
Summary
Induced pluripotent stem cells (iPSCs) can trigger immune responses in recipients, contrary to expectations for autologous therapies. This study reveals that iPSC-derived cells, unlike embryonic stem cells (ESCs), can be immunogenic, necessitating pre-clinical evaluation.
Area of Science:
- Stem Cell Biology
- Immunology
- Regenerative Medicine
Background:
- Induced pluripotent stem cells (iPSCs) are a promising source for regenerative medicine due to their autologous potential.
- It is generally assumed that iPSC-derived cells are immune-tolerant, but their immunogenicity requires rigorous examination.
Purpose of the Study:
- To investigate the immunogenicity of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in syngeneic mouse models.
- To determine if iPSC-derived cells elicit immune responses in the host, potentially impacting their therapeutic application.
Main Methods:
- Teratoma formation assays were performed using allogeneic and syngeneic ESCs and iPSCs (derived via retroviral and episomal methods).
- Immunogenicity was assessed by observing teratoma growth, immune cell infiltration (T cells), tissue damage, and regression.
- Global gene expression analysis was conducted on teratomas to identify differentially expressed genes.
Main Results:
- Allogeneic ESCs were rejected, while syngeneic ESCs formed teratomas without immune rejection.
- Teratomas derived from syngeneic iPSCs (both retroviral and episomal) showed significant immune rejection and T cell infiltration.
- Gene expression analysis revealed overexpression of specific genes in iPSC-derived teratomas that contribute to immunogenicity.
Conclusions:
- Unlike ESCs, iPSC-derived cells can induce T-cell-dependent immune responses in syngeneic recipients.
- Abnormal gene expression in differentiated iPSCs can lead to immunogenicity.
- Therapeutic application of patient-specific iPSC-derived cells requires thorough evaluation of their immunogenicity prior to clinical use.
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