Induced pluripotent stem cells (iPS cells, or iPSC) were first described in a 2006 paper from Shinya Yamanaka, which demonstrated that somatic cells (cells aside from germ cells and gametes) from mice can be converted into pluripotent stem cells. Yamanaka and his research partners then derived human iPS cells from adult fibroblast cells in 2007.Because pluripotent stem cells can differentiate into virtually any cell type in the body, iPS cells have come to be featured in an abundance of research and innovative medical applications.
Induced pluripotent stem cells are immature stem cells derived from adult somatic cells in the body. As a type of pluripotent stem cell, iPSC can differentiate into other types of cells after receiving the appropriate stimulation.
The typical procedure for generating iPS cells involves introducing genes called “reprogramming factors” that are linked to pluripotency in a mature cell type. Introducing such reprogramming factors to mature somatic cells induces them to dedifferentiate into iPS cells in a matter of weeks, at which point the resulting iPS cells can be stimulated to differentiate into specific cell types, depending on the treatment needs.
Embryonic stem cells are another type of pluripotent stem cell, with the same ability to become any type of cell that iPS cells have. That said, isolating stem cells can damage or destroy the embryo, which poses ethical concerns over using embryonic stem cells in research and treatment applications.
Meanwhile, induced pluripotent cells can be generated from cells that have already matured, so iPS cell research poses no risk to a developing embryo. Furthermore, culturing iPSC from adult tissue generates patient-specific lines of pluripotent stem cells, which can differentiate into cells that are a perfect match for the donor. These factors allow iPS cell therapies to avoid ethical quandaries and reduce the risks of a negative immune response or tissue rejection for transplant or regenerative treatment patients.
Perhaps the most promising aspects of induced pluripotent stem cell research involve the ability to custom-tailor tissue repair, pharmaceutical treatment, or transplant procedures for each patient. Because iPS cells are cultivated directly from a patient’s cellular tissue, the cells they differentiate into are genetic matches for the patient. Genetic compatibility with tissues generated from iPS cells minimizes the likelihood that a patient’s immune system will reject regenerated or transplanted tissue, and allows for specific drug therapies to be tested on a patient’s “own” cells or tissues in vitro, giving medical teams insight into how the patient might respond to a given treatment plan.
That said, given that iPS cell research is a relatively new field of biotechnology, there are several drawbacks to be solved before iPS cell therapies can become regular treatment options. For one, processes for converting adult cells to iPS cells are relatively inefficient. In addition, introducing reprogramming factors to the somatic cells carries the risk of introducing genetic mutations to the target cell’s genome.
Induced pluripotent stem cell differentiation brings similar promise to immunobiology and immunotherapy. One area of interest involves differentiating iPSC to T cells to study the behavior of T cells in vitro as well as develop patient-specific treatment applications.
For example, iPSC-derived T cells have been shown to preserve the T cell receptor (TCR) structure of the parent T cell. In this case, mature T cells are reprogrammed into iPSC, which are then stimulated to differentiate into new T cells. The TCRs on these new T cells retain their antigen-specific binding, activation, and cytotoxic capabilities. A recent study found that iPSC-derived T cells demonstrate anti-tumor activity in vivo, suggesting the potential to develop personalized iPSC T cell therapies for cancer patients. Moreover, the telomeres at the ends of the DNA strands in these iPSC-derived T cells are elongated compared to their progenitors, allowing iPSC-derived T cells to endure more proliferation with a lower risk of decay or mutation to the DNA contained in the cells.
To perform an iPSC T cell differentiation protocol in a lab, researchers must obtain a sample of mature T cells from a patient, and acquiring T cells from a blood sample requires performing cell sorting, cell separation, or cell isolation procedures.
Traditional methods for cell sorting involve subjecting samples to intense mechanical, magnetic, or radiative environments, which pose risks to the health of the T cells in the sample. Furthermore, cell separation protocols like Fluorescence-Activated Cell Sorting or Magnetic Activated Cell Sorting typically involve expensive equipment that can require specialized training to operate.
Meanwhile, Buoyancy Activated Cell Sorting (BACS) using microbubble technology from Akadeum Life Sciences is an affordable, easy-to-use, and effective alternative for isolating rare immune cells such as some T cell subsets or iPSC. BACS with microbubbles involves labeling unwanted cells or cellular debris in a sample with antibodies, then gently floating those cells to the surface of the sample to be discarded, leaving behind a pure and viable solution of the desired T cells. Akadeum offers T cell isolation products for separating mouse and human naïve T cells, CD4+ T cells, and naïve CD4+ T cells ready to kick off any iPSC T cell differentiation protocol.