Dr. Mitchell Weiss, Dr. Monica Bessler, Dr. Philip Mason and their entire team at The Children’s Hospital of Philadelphia have shown that skin cells from patients with DBA can be reprogrammed to produce blood cells. This breakthrough work is a step forward in understanding DBA and could lead to exciting new approaches in gene therapy and treatment options.

For many years, physicians and scientists have been trying to find out what goes wrong with the blood in patients with Diamond Blackfan Anemia and why they can’t make the same number of red blood cells as other people. The answer most likely can be found by studying the bone marrow precursor cells that are destined to become red blood cells. Unfortunately, there are very few of these cells in the bone marrow of DBA patients. In addition, obtaining these cells requires bone marrow sampling, which can be painful and inconvenient for the patient. Some progress has been made by generating “human DBA-like mutations” in other species such as yeast, flies, fish and mice and these models have been used in research efforts. However, human based experimental systems for studying DBA have been unavailable.

Now a breakthrough has been made by a collaborating group of scientists working at The Children’s Hospital of Philadelphia and has been published in BLOOD (http://www.ncbi.nlm.nih.gov/pubmed/23744582). These investigators found that skin cells taken from a DBA patient can be reprogrammed in a test tube to make stem cells, called induced pluripotent stem cells or iPS cells. iPS cells are capable of producing red blood cells when cultured under the correct conditions. Similar to the patients from whom they have been derived, iPS cells from DBA patients make red cells inefficiently when compared with iPS cells from other people. However, when the mutation that caused DBA is corrected, the patient derived iPS cells make red blood cells normally.

Thus, scientists can now use a patient’s iPS cells to investigate at the level of individual molecules exactly what goes wrong in DBA. What’s more, the stem cells made in this way are unique to each patient. These tools should allow some important questions about DBA to be answered. For example, why are some patients only mildly affected while others are dependent on blood transfusions?

Comparison of iPS cells from these patients might reveal the answer. The DBA iPS cells can also be used for preclinical studies to test and develop new drugs that may improve blood production in DBA patients. In the longer term, it may one day be possible to use iPS or similar cells to produce blood cells that can be used for bone marrow transplantation or transfusion therapies. Although much work still needs to be done, development of iPS cells from DBA patients represents a new step towards better understanding and curing this disease.

Most importantly, these exciting advances would not have been possible without the support of DBA patients and their families and their willingness to participate in research studies. (For more information and/or study participation in iPSC research for DBA, contact Weissmi@chop.edu and Besslerm@email.chop.edu).