Kidney News August 2011 3#8 : Page 3
August 2011 | ASN Kidney News | 3 Stem Cells Continued from page 1 can be generated from patients with certain genetic disorders. In the current study, investigators questioned whether terminally differ-entiated kidney cells could be repro-grammed to pluripotency so that the resulting stem cells could differenti-ate into all three germ layers. To answer this, Ricardo and her colleagues used normal human me-sangial cells to derive iPS cell lines via genetic programming that con-sisted of transfection of 293FT cells with retroviral vectors containing the genes OCT3/4, SOX2, KLF4 , and c-Myc . After several days, mesangial cells were reseeded on mouse em-bryonic fibroblast feeders. From 5 × 104 normal human mesangial cells, an average of 40 iPS colonies was ob-served. Numerous in vitro tests dem-onstrated that the kidney-derived iPS (kiPS) cells resembled human embryonic stem cell–like colonies in morphology and gene expression. For example, they were alkaline phos-phatase positive; expressed OCT3/4, TRA-1-60, and TRA-1-81 proteins; and showed downregulation of me-sangial cell markers. The kiPS cells expressed genes analogous to embry-onic stem cells and showed silencing of the retroviral transgenes by the fourth passage of differentiation. In addition, the kiPS cells formed em-bryoid bodies and expressed markers of all three germ layers. To test the cells’ pluripotency in vivo, three immunodeficient mice were injected with kiPS colonies. En-capsulated cystic teratomas formed in all mice and showed differentiated tissues from all three germ layers. “Our study for the first time pro-vides proof-of-concept for the direct nuclear reprogramming of adult hu-man mesangial cells to generate kiPS cells,” the authors wrote. kidney disease.” Ricardo noted that through the study of an individual patient’s iPS cell line, researchers may be able to optimize that patient’s preventive and therapeutic care. Others in the field are interested to see what advances come next. “This article shows that the renal field, like many others, is embracing the possi-bility that iPS cell generation may act as a source of stem cells for eventual use in the repair of kidney disease,” said Melissa Little, PhD, of the Uni-versity of Queensland in St. Lucia, Queensland, Australia. “It should also be possible to make such cells from patients with genetic diseases such as polycystic kidney disease and poten-tially use them as tools to better un-derstand such diseases,” she added. Paola Romagnani, MD, of the Uni-versity of Florence in Italy, noted that the research may also advance drug development. “Mesangial cell–derived iPS cells may be helpful for screening of novel pharmacological compounds for treatment of these renal disorders,” he said. The study shows that human kid-ney biopsy specimens are a viable starting source for the generation of iPS cells,” Little said, but “what this does not address is how to take these cells and then regenerate useful renal cells for treatment.” To date, no one has developed a way of directing the differentiation of such cells into a kid-ney cell type. Implications for the clinic Patient-derived iPS cell lines gener-ated by reprogramming somatic cells could have considerable importance in the clinic. “Induced pluripotent cells hold tremendous promise for stem cell and regenerative medicine,” said Benjamin Humphreys, MD, who is codirector of the Harvard Stem Cell Institute’s Kidney Group and was not involved with the re-search. “Since iPS cells appear to re-tain some molecular memory of their tissue of origin, this demonstration that kidney mesangial cells can be reprogrammed to pluripotency is an important step forward in developing this technology for disease modeling, toxicity testing, and ultimately cell therapy for patients suffering from Kidney Week AmericAn Society of nephrology 2011 pennsylvania convention center philadelphia, pennsylvania Kidney Week 2011: November 8 – 13 Exhibit Dates: November 10 – 1 2 Register online at www.asn-online.org/KidneyWeek
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