Stem Cells and Development · 2009 · 203 citations · 33 references
Life SciencesCell BiologyDevelopmental BiologyCell TherapyRegenerative MedicineStem Cell BiologyEmbryonic Stem CellsGene Delivery To Stem CellsOrgan RegenerationPluripotent Stem CellsStem Cell DifferentiationStem Cell ReprogrammingEmbryonic Stem Cell BiologyGrowth FactorsInduced PluripotencyInduced Pluripotent Stem CellsPluripotent Stem Cell DifferentiationSpermatogonial Stem Cell BiologySpermatogonial Stem Cell NicheStem Cell-based Organ Regeneration
Adult tissue cells, including spermatogonial stem cells, can be reprogrammed to pluripotent, ES‑like cells—sometimes without viral gene delivery—and these cells can differentiate into all three germ layers and organ lineages. Using 1‑g testis biopsies from organ donors, the authors isolated germ cells, removed them from their niche, and cultured them in embryonic stem cell medium with growth factors, thereby reprogramming them to pluripotent ES‑like cells. The resulting pluripotent ES‑like cells from SSCs hold promise for autologous organ regeneration, and the authors’ simplified protocol may be more clinically applicable than existing methods.
Recent reports have demonstrated that adult tissue cells can be induced to pluripotency, the iPS cells, mostly with the addition of genes delivered using viruses. Also, several publications both in mouse and in human have demonstrated that spermatogonial stem cells (SSCs) from testes can convert back to embryonic stem (ES)-like cells without the addition of genes. Furthermore, these pluripotent ES-like cells can differentiate into all three germ layers and organ lineages. Thus, SSCs have great potential for cell-based, autologous organ regeneration therapy for various diseases. We obtained testes from organ donors and using 1 g pieces of tissue (biopsy size) we demonstrate that testis germ cells (putative SSCs and/or their progenitors) reprogram to pluripotency when removed from their stem cell niche and when appropriate growth factors and reagents in embryonic stem cell medium are added. In addition, our method of obtaining pluripotent ES-like cells from germ cells is simpler than the described methods and may be more suitable if this procedure is developed for the clinic to obtain pluripotent cells to cure disease.
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