Growing platelets from hematopoietic stem cells may be a small step in science, but a leap in transfusion medicine
Community blood drive efforts go on every day. The need for life-saving packed red blood cell units, peripheral blood mononuclear cells, plasma units, and platelet units is endless. Our quest for continuous improvement in transfusion medicine and in the quality of life in general takes us on an exploratory path seeking reliable manufacture of clinical grade cells. The production of platelets from stem cells is one arm of these investigations.
Platelets are small fragments that bud off from megakaryocytes – a certain blood cell that originates from bone marrow stem cells. In a microliter of blood, there are ~250,000 platelets. They are sized at about a twentieth that of a red blood cell. The importance of platelets comes from their ability to migrate to damaged blood vessels to plug up leaks and damages.
Scientists have been able to generate platelets in cell culture from cord blood stem cells, human embryonic stem cells, and induced pluripotent stem cells. While yields achieved by these strategies have not been sufficient for clinical purposes, the experiments do demonstrate proof of concept. One limitation that has been recognized is the need for technologies to scale up megakaryocytes in culture.
In the bone marrow, megakaryocytes arise from the differentiation of hematopoietic stem cells. Each megakaryocyte may release between 2000 to 5000 platelets. To achieve this, megakaryocytes grow their DNA content by becoming polyploid or having upwards of a 100 sets of chromosomes per cell. This allows for the production of proteins and organelles necessary to assemble platelets.
In the research lab, one feature that is being investigated in manufactured platelets is the concept of generating HLA class I deficient platelets. This genetic modification would cater to the group of patients who are heavily transfused and who develop HLA-related platelet refractoriness because they are immunized by repeated non-self platelet dosing.
HemaCare provides hematopoietic stem cells from cord blood, mobilized PBMC, and bone marrow, to support efforts towards achieving the clinical grade manufacture of platelets. Specifically, we can generate megakeratocytes from the bone marrow. Additionally, HemaCare supplies myeloid cells, CD34+ cells and CD133+ cells.
1: Avanzi MP, Mitchell WB. Ex vivo production of platelets from stem cells. Br J Haematol. 2014 Apr;165(2):237-47. PMID: 24521452.