Krencik R, Weick JP, Liu Y, Zhang ZJ, Zhang SC.
Specification of transplantable astroglial subtypes from human pluripotent stem cells.
Nat Biotechnol. 2011 Jun;29(6):528-34.
PubMed.
This work is very interesting because it shows that astrocytes can be successfully differentiated from human iPS cells (ES cells being less relevant, in my point of view). The paper is mostly oriented toward showing that astrocytes are functional. This is convincingly shown both in vitro and after graft in mouse brain.
Generating functional astrocytes from human iPS cells will be very valuable for fundamental studies to better understand their development and function in vitro and in vivo. However, the cells in this study were obtained from cell lines. To bring this technology to the study of ALS, this work needs to be done using the patient’s cells. This should be quite feasible, starting from a small skin biopsy, to generate iPS cells from fibroblasts. The next step is more challenging: to show that the ALS phenotype of astrocytes (still largely unknown) will be re-expressed in these cells even though they derived from iPS cells. In other words, it is not clear at this point if a patient-derived fibroblast transformed into an iPS cell, and then differentiated into an astrocyte, will express the same disease characteristics than a native astrocyte from the patient's spinal cord.
Demonstrating this re-expression of the ALS phenotype from iPS cells would be a major breakthrough.
Another potential approach could be a cell therapy, using the patient's own cells to generate iPS cells and astrocytes in order to graft back these autologous astrocytes in the patient brain or spinal cord. However, such an approach is purely speculative, since there is no clear evidence up to now that it could be beneficial, at least for ALS.
In conclusion, this work is an encouraging step in the long process to develop in-vitro models of ALS and, perhaps one day, a cell transplantation therapy (which is pure speculation today).
Comments
LOEX, Université Laval
This work is very interesting because it shows that astrocytes can be successfully differentiated from human iPS cells (ES cells being less relevant, in my point of view). The paper is mostly oriented toward showing that astrocytes are functional. This is convincingly shown both in vitro and after graft in mouse brain.
Generating functional astrocytes from human iPS cells will be very valuable for fundamental studies to better understand their development and function in vitro and in vivo. However, the cells in this study were obtained from cell lines. To bring this technology to the study of ALS, this work needs to be done using the patient’s cells. This should be quite feasible, starting from a small skin biopsy, to generate iPS cells from fibroblasts. The next step is more challenging: to show that the ALS phenotype of astrocytes (still largely unknown) will be re-expressed in these cells even though they derived from iPS cells. In other words, it is not clear at this point if a patient-derived fibroblast transformed into an iPS cell, and then differentiated into an astrocyte, will express the same disease characteristics than a native astrocyte from the patient's spinal cord.
Demonstrating this re-expression of the ALS phenotype from iPS cells would be a major breakthrough.
Another potential approach could be a cell therapy, using the patient's own cells to generate iPS cells and astrocytes in order to graft back these autologous astrocytes in the patient brain or spinal cord. However, such an approach is purely speculative, since there is no clear evidence up to now that it could be beneficial, at least for ALS.
In conclusion, this work is an encouraging step in the long process to develop in-vitro models of ALS and, perhaps one day, a cell transplantation therapy (which is pure speculation today).
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