Reprogramming Stem Cells to Treat, Study Disease

First produced in the past decade, induced pluripotent stem cells — which are derived from adult cells — are capable of developing into many cell types. In two new studies, investigators from The Children’s Hospital of Philadelphia reprogrammed skin cells from patients with rare disorders into induced pluripotent stem cells (iPSCs), highlighting the great promise these cells hold.

“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, led a study of induced pluripotent stem cells in Diamond Blackfan anemia — a rare congenital blood disorder — published in June in Blood. 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 Diamond Blackfan anemia (DBA), a mutation prevents a patient’s bone marrow from producing normal quantities of red blood cells, resulting in severe, sometimes life-threatening anemia, which can make it difficult for researchers to discern the underlying mechanism of the disease. According to the Diamond Blackfan Anemia Foundation, there are 25 to 35 new cases of the disease a year in the U.S., with more than 90 percent of patients showing symptoms in the first year of life. 

In the June study, the researchers removed skin cells from Diamond Blackfan Anemia patients and reprogrammed the cells into induced pluripotent stem cells. When those iPSCs were stimulated to form blood tissues, like the patient’s original mutated cells they produced a deficient amount of red blood cells. But 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. Nonetheless, the patient-derived iPSCs are highly useful as a model for investigating blood disorders, Dr. Weiss noted. 

Meanwhile, the study of juvenile myelomonocytic leukemia (JMML) published in April provides a concrete example of using iPSCs for drug testing, specifically for the rare and often-aggressive childhood leukemia JMML. The study team generated iPSCs from two children with JMML, and then manipulated the iPSCs in cell cultures to produce cells that multiplied uncontrollably, much as the original JMML cells do.

They then tested the cells with two drugs, one of which reduced the proliferation of cancerous cells in culture. “This provides a rationale for a potential targeted therapy for this specific subtype of JMML,” said Dr. Weiss.

For more details about both studies, see the full press release.