Pluripotent Stem Cells - A Novel Source of Haematopoietic Cells for Transplantation and Transfusion Medicine

Haematopoietic stem cells (HSCs) are commonly used to reconstitute the bone marrow and blood of patients suffering from diseases such as leukaemias, lymphomas and non-malignant conditions like severe bone marrow aplasia and thalassemia major. The mature progeny of HSCs, especially erythrocytes and platelets, are used regularly for rapid transfusion into patients with acute conditions like life-threatening bleeding. For HSC transplantation (HSCT), cells must originate from an immunologically matched donor, and the chronic lack of supply of suitable cells drives the search for alternate HSC sources. Human embryonic stem cells (hESCs) hold the promise for development into every tissue type. Multiple laboratory based studies have demonstrated the careful, ontological approach to HSC differentiation from hESCs, leading to the differentiation of cells which are similar to bone marrow HSCs. Significant challenges remain in achieving HSC replicas, primarily improvement to both efficiency of HSC generation and sustained engraftment in vivo. The differentiation of mature blood cells from hESCs, in order to generate large numbers of “off the shelf” cells for transfusions, has been successful with the production of seemingly fully mature and functional cells, albeit in low numbers. Concerns about the need for immunosuppression after hESC transplantation, has meant that the development of patient-specific induced pluripotent stem cells, which have also been differentiated into blood cells, also has enormous potential for use in the clinic. Presently, these cell products have significant barriers to overcome before clinical translation, such as efficient in vivo function, large-scale manufacture of consistent cell products and short- and long-term safety issues.

Keywords: Haematopoietic stem cells, embryonic stem cells, immunosuppression, transpalantion.