Umbilical Cord Blood Found To Be Ready Source For Off-The-Shelf, Patient-Specific, Induced Pluripotent Stem cells

Umbilical cord blood cells can successfully be reprogrammed to function like embryonic stem cells, thus setting the basis for a comprehensive bank of tissue-matched, cord blood-derived induced pluripotent stem (iPS) cells for off-the-shelf applications.

Worldwide, there are already more than 400,000 cord blood units banked along with immunological information. Cells found in umbilical cord blood contain a minimal number of cell mutations and possess the immunological immaturity of newborn cells, allowing the HLA donor-recipient match to be less than perfect without the risk of immune rejection of the transplant.

Human leukocyte antigen (HLA) typing is used to match patients and donors for bone marrow or cord blood transplants. HLAs are special surface markers found on most cells in the body and help the immune system to distinguish between "self" and "non-self." Selecting common HLA haplotypes from among already banked cord blood units to create iPS cell would significantly reduce the number of cell lines needed to provide a HLA match for a large percentage of the population.

Since the first adult cells were converted into iPS cells, they have generated a lot excitement as an uncontroversial alternative to embryonic stem cells and as a potential source for patient-specific stem cells. Unfortunately, taking a patient's cells back in time is not only costly, but could be difficult when those cells are needed right away to mend injured spinal cords or treat acute diseases, and outright impossible when the effects of aging or chronic disease have irrevocably damaged the pool of somatic cells.

"Patient-specific iPS lines have been advocated as a theoretically ideal clinical option to regenerate tissue but from a practical and cost-benefit aspect, this approach may not be feasible," said Juan-Carlos Izpisúa Belmonte, Ph.D., a professor in the Salk Institute's Gene Expression Laboratory and lead researcher on this study done at the Salk Institute for Biological Studies and the Center for Regenerative Medicine in Barcelona, Spain.  Belmonte suggests that the, "large scale production and banking of cord blood-derived iPS lines in a publically available network could be a viable alternative for future clinical applications."

With this in mind, Belmonte and his colleagues set out to transform hematopoietic stem cells isolated from cord blood into iPS cells. They not only successfully converted them using only two out of the four most commonly used factors—OCT4 and SOX2—but also in less time than any other previously published methodology require. No matter, whether the researchers started with freshly collected cord blood or previously frozen samples, the resulting iPS cells were indistinguishable from human embryonic stem cells. 

"The population of cord blood cells used for reprogramming express reprogramming/stem cell factors at higher levels than those found in other adult somatic cells, which could explain why cord blood cells can be reprogrammed with less factors and in less time," says Izpisúa Belmonte. "It's almost like they are already half-way there."

In addition, the cord blood-derived iPS cells, CBiPS cells for short, passed all standard tests for pluripotency: They gave rise to stem cell tumors known as teratomas and differentiated into derivatives of the three embryonic tissue layers, including rhythmically beating cardiomyocytes and dopamine-producing neurons.

Izpisúa Belmonte's next goal is to convince cord blood cells to burn back time using methods that are considered safe for clinical applications in humans. The original protocols for producing iPS cells—including the one used by Belmonte and his team—rely on the integration of foreign "reprogramming" genes into the host-cell genome, a process associated with risks including mutation and the development of cancers after iPS-cell transplantation, limiting their therapeutic value. Several labs are working on creating iPS cells from adult cells without reprogramming with genes.

Adapted from the Salk Institute La Jolla announcement through EurekAlert.