Over the past five years, stem cell researchers have learned how to induce or reprogram skin cells to become pluripotent stem cells—cells capable of becoming any type of cell in the body. The result: induced pluripotent stem cells or iPSCs. Scientists have also discovered how to reprogram cells to become precursor or progenitor cells. Precursor cells have a much narrower range of potential for development. They are able to become one very specific type of cell in the body.
Expanding on previous work, the latest breakthrough achieves a kind of “goldilocks” or just-right level. Working with mice, the team led by Hans Schöler discovered how to reprogram fully differentiated skin cells into neuronal stem cells (NSC)s. Unlike pluripotent cells, NSCs are far more suitable for clinical use. And now, with this breakthrough, the Max Plank Institute team has learned how to reprogram or induce NSCs or iNSCs.
And unlike precursor or progenitor cells, iNSCs are capable of multiplying and diffentiating once they are implanted. When researchers implanted their iNSCs into mouse brains, iNSCs generated new cells that began to take on some of the characteristics of ordinary developing brain cells.
Caption: This is an immunofluorescence microscopy image of the induced neural stem cells (iNSCs) using antibodies against two neural stem cell markers SSEA1 (red color) and Olig2 (green color). Credit: MPI for Molecular Biomedicine
The field of stem cell research has faced many obstacles, some moral and some medical. The main moral objection is that the prime source of human pluripotent cells is the human embryo, and many object to the destruction of the embryo for medical purposes. One of the medical challenges is that implanted cells are likely to be rejected by the immune system, much as transplanted organs are rejected unless immunosuppressant drugs are given.
Unless, of course, the source of the cells is from the patient’s own body. That’s why this achievement is important. If this technique can be applied to human cells—and there’s no reason to think it can’t—then someday it may be possible to take a small sample of cells from a patient’s skin, convert them to iNSCs, and then implant them in the patient’s brain to repair damage from disease or injury.
Not only does the iNSC discovery use the patient’s own cells as the source. It also by-passes the pluripotent stage. That fact should help researchers avoid creating cancer or other problems.
According to Schöler, "pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumours instead of regenerating a tissue or an organ."
"Our research shows that reprogramming somatic cells does not require passing through a pluripotent stage," Schöler said in a press release issued by the Max Plank Institute. "Thanks to this new approach, tissue regeneration is becoming a more streamlined—and safer—process."
The article, "Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors," appears in the March 22 issue of Cell Stem Cell.