Reprogramming Stem Cells Offers Powerful Tool

First produced in the past decade, induced pluripotent stem cells (iPSCs) are capable of developing into many or even all human cell types. In two recent studies, scientists reprogrammed skin cells from patients with rare blood disorders into iPSCs, highlighting the great promise of these cells in advancing understanding of those challenging diseases — and eventually in treating them.

“The technology for generating these cells has been moving very quickly,” said the studies’ leader, Mitchell J. Weiss, MD, PhD. “These investigations can allow us to better understand at a molecular level how blood cells go wrong in individual patients — and to test and generate innovative treatments for the patients’ diseases.”

Dr. Weiss, a hematologist and stem cell researcher, along with CHOP’s Monica Bessler, MD, Philip Mason, PhD, and Deborah L. French, PhD, published a study on iPSCs and Diamond Blackfan anemia, a rare congenital blood disorder. Another study published by Dr. Weiss and his team in the same journal on April 25 focused on iPSCs in the childhood cancer juvenile myelomonocytic leukemia.

In the June Blood study, the researchers removed fibroblasts (skin cells) from DBA patients and using proteins called transcription factors reprogrammed the cells into iPSCs. As those iPSCs were stimulated to form blood tissues, like the patient’s original mutated cells, they were deficient in producing red blood cells. However, when the researchers corrected the genetic defect that causes DBA, the iPSCs developed into red blood cells in normal quantities.

“This showed that in principle, it’s possible to repair a patient’s defective cells,” said Dr. Weiss, who cautioned that this finding is an early step, with further studies needed to verify if this approach will be safe and effective in clinical use.

The study of juvenile myelomonocytic leukmia published in April, meanwhile, provides a concrete example of using iPSCs for drug testing, specifically for the rare and often-aggressive childhood cancer juvenile myelomonocytic leukemia. And a long-term goal of this line of research, said Dr. Weiss, is for iPSC lines generated by researchers to provide the raw materials for eventual cell therapies that could be applied to specific genetic disorders.