Quick answer
What types of pluripotent stem cells are there?
The reviews summarized here focus on pluripotent stem cells, which come in more than one form12. Embryonic stem cells are pluripotent cells of embryonic origin2. Induced pluripotent stem cells are somatic cells reprogrammed to pluripotency, and one review describes them as expandable to an almost unlimited degree and able to mature into most somatic cell types12.
What are pluripotent stem cells?
Pluripotent stem cells renew themselves and keep, at the same time, the ability to mature into many other cell types13. One review credits human iPSCs with two traits: they can keep dividing for long periods, and they can turn into nearly any cell type in quantities that are not limited3. A second review notes that these cells can expand to an almost unlimited degree and can be matured into most of the body's somatic cell types1. A third puts their range at all three germ layers2. The reviews treat self-renewal and pluripotency as the reasons these cells suit disease modeling and regenerative medicine2. The reviews describe more than one route to a pluripotent cell, and those routes differ in where the starting material comes from12.
Where do embryonic stem cells fit in?
Embryonic stem cells are pluripotent cells of embryonic origin, and a review that compares them with iPSCs notes that they are allogeneic2. The same review reports that iPSCs were found not to affect the host immune system2. It also notes that iPSC lines can be sourced from patients, including people with rare diseases, and that harvesting can be non-invasive2. Both cell types are therefore described as pluripotent, while the material they start from differs2.
| Cell type | Starting point | Noted in the reviews | Source |
|---|---|---|---|
| Embryonic stem cells | Human embryos | Allogeneic; pluripotent | 2 |
| Induced pluripotent stem cells | Reprogrammed somatic cells | Pluripotent and expandable; patient-specific lines possible | 12 |
| iPSC-derived cells | Differentiation of iPSC lines | Disease models and drug screening | 1 |
| Autologous iPSC therapy | The patient's own cells | In development as a cell therapy | 1 |
| Allogeneic iPSC therapy | A donor-derived line | In development as a cell therapy | 1 |
How are induced pluripotent stem cells made?
Induced pluripotent stem cells are made by reprogramming a somatic cell until it regains pluripotency, a step that reshapes the epigenetic landscape considerably13. The earliest approach described in a review of the field introduced four transcription factors, Oct3/4, Sox2, Klf4 and c-Myc, known together as OSKM, into fibroblasts2. The technology was introduced in 20062. Human iPSCs have also been derived with Oct4, Sox2, Nanog and Lin28, which the review says indicates that pluripotency can be reached through different sets of factors2.
DNA methylation and histone tail modifications are among the changes that help set a somatic cell's gene expression back to a self-renewing, pluripotent pattern3. Delivery falls into integrative and nonintegrative systems using viral or nonviral vectors, and each has been assessed for efficiency and quality2. A lentiviral vector has been documented with a reprogramming efficiency of between 0.1 and 1%2. Later work replaced c-Myc with the microRNAs miR-291-3p, miR-294 and miR-295 and produced homogenous colonies of human iPSCs2. Efficiency matters because the review lists roadblocks to conversion, among them loss of the somatic program, the switching on of endogenous pluripotency genes and the late activation of the Nanog locus2.
The review tabulates the strategies and what each one was reported to achieve2.
| Strategy | What it uses | Reported in the review | Source |
|---|---|---|---|
| Viral integrative | Integrating viral vector | First iPSCs; incomplete pluripotency gene expression | 2 |
| Lentiviral vector | Viral delivery of the factors | Efficiency of between 0.1 and 1% | 2 |
| Nonviral integrative | Two plasmids, one carrying c-Myc | Low efficiency; possible integration | 2 |
| Nonintegrative nonviral | Self-replicating vectors or cytoplasmic RNA | Easy to use; lower efficiency than lentiviral | 2 |
| MicroRNA-based | MicroRNAs in place of c-Myc | Improved efficiency; homogenous colonies | 2 |
What can researchers do with iPSCs?
iPSCs are used to model human development and disease, to screen drugs and to develop cell therapies1. The models range from cultures of a single cell type to three-dimensional organoids, and they serve high-throughput drug screening1. The review notes that iPSCs can be genetically engineered, which broadens what researchers can do with a single line1. Both reviews place iPSC work within regenerative medicine12.
- Neurological disorders, COVID-19 and cancer are used as examples of disease-specific phenotypes modeled with iPSC-derived cells1.
- Cardiac disease and inherited arrhythmias are among the conditions studied with iPSC models2.
- Alzheimer's disease, liver disease and spinal cord injury are also modeled2.
- For Parkinson's disease, the work has reached a clinical trial: researchers began testing neurons derived from iPSCs after in vivo studies went well2.
The reviews describe autologous and allogeneic iPSC-based cell therapies as being developed for human diseases, with the details still taking shape1.
What is still being studied?
Two themes recur across the reviews: how uniform iPSC-derived cells are, and how stable their genomes remain34. Genetic abnormalities may already sit in donor somatic cells, or appear while the cells are reprogrammed or kept in culture, and one review recommends checking genetic integrity at regular intervals3. The same review notes that residual epigenetic memory from the original cell influences the iPSC phenotype3. A review on cellular heterogeneity attributes variation to donors, tissue sources, methodologies and analytical challenges4.
That review proposes practical responses, including differentiation protocols improved with new media morphogens, biomaterials, three-dimensional culture and mechanical stimulation4. The same review asks for agreed standards on producing and using cell lines and neo-tissues, for detailed characterization of them, and for a system of central banks in which cells are registered4. The same review points to analytical tools and artificial intelligence applied to omics datasets as ways to help tell cell types apart inside mixed populations and to spot the factors behind off-target differentiation4. The authors also suggest that a degree of heterogeneity may be necessary for lab models meant to reproduce the body closely4.
Frequently asked questions
Are embryonic stem cells and induced pluripotent stem cells the same?
No. Embryonic stem cells are pluripotent cells of embryonic origin with an allogeneic trait, while induced pluripotent stem cells are made by reprogramming somatic cells, which allows patient-specific lines to be generated2.
Can induced pluripotent stem cells become any cell type?
One review describes them as able to mature into practically any cell type, in unlimited numbers3, and another says all three germ layers are within their range2. A third puts it at most somatic cell types1.
Why does reprogramming efficiency vary between methods?
The review reports different recorded efficiencies depending on the method: between 0.1 and 1% for lentiviral vectors, and lower efficiency for nonintegrative nonviral systems2. The roadblocks it lists include late activation of the Nanog locus2.
