Induced Pluripotent Stem Cells from Bone Marrow-Derived, Peripheral Blood-Derived Hematopoietic Cells and Cord Blood.

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As mentioned in a previous article—Public and Private Cord Blood Banking: United We Stand!—umbilical cord blood obtained from the umbilical cord and placenta is a rich source of MSPC’s and HSPC’s; the latter can be used for transplantation to treat a range of malignant, genetic, metabolic, and immune disorders. In fact, it was shown that cord blood HSPC’s are more proliferative and have a greater chance of matching family members than stem cells from bone marrow. Additionally, cord blood is not only widely available and easily accessible—collection is relatively non-invasive, safe and painless—but its derived HSPC’s can even be safely infused when they are an incomplete match for the recipient due to their immunologically naïve quality.

Given the importance of bone marrow and cord blood transplants, the growing numbers of patients requiring them, their growing availability and the quality of those units, one can only wonder if those cells wouldn’t make better candidates for not only inducing pluripotency but also in making pluripotent cells of better quality for clinical use once the difficulties discussed in the previous article are overcome. Indeed, nuclear and mitochondrial mutations in adult stem cells and differentiated somatic lineages appear to accumulate over a lifetime and have been suggested to contribute to aging and cancer formation.

After many efforts, it was found that mature bone marrow derived hematopoietic cells were indeed reprogrammable into pluripotent cells, however it was more difficult than in fibroblast cells. Indeed, they initially required previous transdifferentiation into adherent macrophage-like cells through retroviral overexpression of the myeloid transcription factor CCAAT/enhancer-binding protein-beta. It was later found that less mature bone marrow derived hematopoietic cells were more easily reprogrammable into pluripotent cells.

Peripheral blood derived hematopoietic cells were found to be very bad candidates for inducing pluripotency as they are predominantly nonadherent and slow-cycling. Indeed, researchers were initially simply unable to induce pluripotency unless using G-CSF-mobilization of HSCs, however that was expensive, time consuming and was found to potentially have detrimental effects on individual donors. After many efforts, and without prior stem cell mobilization, several groups were able to induce pluripotency of different mouse and human blood lineages. However, the observed reprogramming efficiencies were typically lower than for fibroblasts.

It was found that cord blood endothelial cells were superior cells for the induction of pluripotent stem cells based on the criteria that they were adherent and actively dividing cells. Furthermore, Giorgetti et al. demonstrated that even frozen cord blood could be used to generate iPSCs with overexpression of OCT4 and SOX2 only. These cells have biological superiority and, thus, could be made available quite rapidly for thousands of patients. For example, children born with cardiac malformations could benefit from CB-iPSC-derived tissue transplants.

In conclusion, it was found that hematopoietic cells from cord blood represent an easily accessible cell source for the derivation of clinically useful iPSCs. Indeed, allogeneic and autologous cord blood from public and commercial CB banking may provide a superior and almost unlimited juvenescent cell source for the production of clinically useful iPSCs.

Y.S.H.

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