Hematopoietic Stem Cells in Regenerative Medicine: Astray or on the Path?

Abstract

Hematopoietic stem cells (HSCs) are the best characterized adult stem cells and the only stem cell type in routine clinical use. The concept of stem cell transplantation laid the foundations for the development of novel cell therapies within, and even outside, the hematopoietic system. Here, we report on the history of hematopoietic cell transplantation (HCT) and of HSC isolation, we briefly summarize the capabilities of HSCs to reconstitute the entire hemato/lymphoid cell system, and we assess current indications for HCT. We aim to draw the lines between areas where HCT has been firmly established, areas where HCT can in the future be expected to be of clinical benefit using their regenerative functions, and areas where doubts persist. We further review clinical trials for diverse approaches that are based on HCT. Finally, we highlight the advent of genome editing in HSCs and critically view the use of HSCs in non-hematopoietic tissue regeneration.

Keywords: Autologous and allogeneic transplantation; Hematopoietic cell transplantation in hematopoietic and non-hematopoietic conditions; Hematopoietic reconstitution; Hematopoietic stem cells.

Fig. 1

Numbers of HCTs performed in Europe in 2012 by donor type and indication. Shown are numbers of HCTs in patients with the indicated donor types and disease groups as reported by the Registry of the European Society for Blood and Marrow Transplantation (EBMT). Total numbers of HCTs are given in brackets. Data were extracted from [25].

Fig. 2

Graft types used for HCTs. Upon harvest, grafts for HCT can be: unfractionated bone marrow, mobilized peripheral blood (PBSC) or cord blood that contain progenitors with multi- or dual lineage differentiation potential together with mature cells of different lineages. Alternative grafts are lineage-depleted cell populations, cell populations that were selectively expanded in vitro, or HSCs transduced with a viral vector encoding an intact copy of a mutated gene. T-LYs cannot reconstitute hematopoiesis, but selected and/or genetically engineered T-LYs (e.g. CAR T cells) could erase leukemic cells. Here, HSCs include hematopoietic stem and progenitor cells. Cell lineages are symbolized using indicated colors as shown in the legend. GR = Granulocyte; MEG-E = megakaryocyte-erythrocyte; MO = monocyte, NK = natural killer; Ly = lymphocyte.