Gene Therapy Combined with Stem Cell Technology Cures Inherited Anemia

The syndrome is caused by mutations in one of 13 Fanconi anemia (FA) genes, and is characterized by bone marrow failure, leukemia, and other cancers. Treatment includes bone marrow transplants to correct the hematological problems. However, patients remain at high risk of developing cancer and other serious health conditions.

Investigators at the Center of Regenerative Medicine (Barcelona, Spain) started by growing somatic cells from Fanconi anemia patients in tissue culture. To correct the hematologic aspect of the disease a normal copy of the mutated gene was introduced into the cells using a viral vector. Then the investigators transformed the repaired cells into induced pluripotent stem (iPS) cells using a combination of transcription factors, OCT4, SOX2, KLF4, and cMYC. The resulting FA-iPS cells were indistinguishable from human embryonic stem cells and iPS cells generated from healthy donors.

The corrected Fanconi-anemia-specific iPS cells gave rise to hematopoietic progenitors of the myeloid and erythroid lineages that were phenotypically normal, that is, disease-free.

"It has been ten years since human stem cells were first cultured in a Petri dish,” said senior author Dr. Juan-Carlos Izpisúa Belmonte, director of the Center of Regenerative Medicine. "The hope in the field has always been that we will be able to correct a disease genetically and then make iPS cells that differentiate into the type of tissue where the disease is manifested and bring it to clinic. We have not cured a human being, but we have cured a cell,” said Dr. Belmonte. "In theory we could transplant it into a human and cure the disease.”

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Center of Regenerative Medicine