Concise Review: Expanding Roles for Hematopoietic Cellular Therapy and the Blood Transfusion Services

Abstract

Hematopoietic stem cells (HSCs) have remained at the forefront of stem cell research for the past 50 years, since the therapeutic potential of bone marrow transplantation was realized. Uniquely, among stem and progenitor cells, research progress has been made in parallel between the laboratory benchtop and hospital bedside during this period. Integral to this work has been the role of the transfusion medicine services in the collection, storage, and processing of HSCs. The next decade promises to bring further developments: with new fields of cellular therapies, stem cell vaccination, and stem cell drug testing opening up. This article summarizes exciting areas of research concerning the behavior and potential clinical applications of HSCs. For the purposes of clarity, we describe in turn the trafficking and transfer of HSCs; ex vivo expansion of HSC units from different sources; and finally, applications of specifically selected subsets of hematopoietic cells and their progeny.

Age-old wisdom concerning cell-based therapies with added knowledge in the stem cell era: our perspectives

“…It is now known that it is the stem cells within the blood transfused which make the most significant contribution to the therapeutic effect, and that these cells complete their life cycle and eventually die off. Since the stem cells in the small quantity of blood are relatively few, their function is of a passive nature wherein these stem cells and the mature cells in blood provide a transient support for a short duration after which the body’s cells take charge of the function 6. That is probably why blood transfusion is not referred to as stem cell transplantation.…”

“…Although this recent attention can be attributed mainly to the catchy terminology associated with “stem cells”, cell-based therapies have been in clinical use for a long time, as evident from established procedures such as blood transfusion,1 bone marrow transplantation,2 and autologous transplantation of tissues, either with a pedicle with the vascular supply intact as in myocutaneous flap surgery, or without a vascular pedicle intact, as in skin transplantation 3. In all these procedures, it is now understood that a proportion of “stem cells” play an important role in producing beneficial results 4–6…”

“…In blood transfusion, the cells transfused are mostly mature adult cells which transiently take on the functions of cells involved in native hematopoiesis and then disappear,6 whereas in bone marrow transplantation, there are more stem cells, which replace the hematopoietic system of the patient and take over the responsibility for hematopoiesis; this could be one of the reasons why bone marrow transplantation came to be known as “hematopoietic stem cell transplantation” after the discovery of stem cells by Till and McCulloch in 1961 7,8. Within the spectrum of cell-based therapies, the ultimate is in vitro fertilization, where two germ cells of male and female origin are made to undergo fusion in a nonphysiological environment and then produce a potential life form, ie, an embryo which is transferred back to the native physiological environment of the uterus of the female gamete donor or a surrogate 9.…”

Feasibility study of red blood cell debulking by magnetic field-flow fractionation with step-programmed flow

“…It is widely used for blood sample enrichment of nucleated cells (leukocytes) for use in diagnostic and therapeutic biomedical applications [2]. The separation mechanism is based on differential cell sedimentation due to the characteristically higher RBC mass density as compared to other blood cells (and the suspending fluid) [3].…”

2012 and beyond

“…The scope of the most common cell therapy, haematopoietic stem cell transplantation, may be widened by increased use of cord blood, matched unrelated donors and haploidentical transplants. Immunotherapy, through donor lymphocyte infusions, antigen specific T cells clones, regulatory T cells and mesenchymal stem cells and other regulatory or effector populations may widen the scope and improve the safety of transplants (Hodby and Pamphilon, 2011). Here, there are many possible innovations but change will probably occur more slowly as there are significant costs and considerable technical difficulties associated with providing new formulations and conducting the necessary trials.…”