The early phase of engraftment after murine blood cell transplantation is mediated by hematopoietic stem cells

Abstract

Blood cell transplantation is largely replacing bone marrow transplantation because engraftment is more rapid. This accelerated engraftment is thought to be mediated by relatively mature committed hematopoietic progenitor cells. Herein, we have used a modified rhodamine (Rho) staining procedure to identify and purify Rho ؉/؉؉ (dull͞bright) and Rho ؊ (negative) subpopulations of hematopoietic progenitor cells in murine cytokine-mobilized blood. The Rho ؉/؉؉ cell population contained >99% of committed progenitor cells with in vitro colony-forming ability. The Rho ؊ cell population contained the majority of hematopoietic stem cells with in vivo marrow repopulating ability. The rate of hematopoietic reconstitution was identical in recipients of grafts containing only purified Rho ؊ stem cells or purified Rho ؊ stem cells in combination with large numbers of Rho ؉/؉؉ committed progenitor cells. In contrast, transplantation of 3-fold more hematopoietic stem cells resulted in accelerated reconstitution, indicating that the reconstitution rate was determined by the absolute numbers of Rho ؊ stem cells in the graft. In addition, we observed a 5-to 8-fold reduced frequency of the subset of hematopoietic stem cells with long-term repopulating ability in cytokine-mobilized blood in comparison to steady-state bone marrow. Our results indicate that hematopoietic stem cells and not committed progenitor cells mediate early hematopoietic reconstitution after blood cell transplantation and that relative to bone marrow, the frequency of stem cells with long-term repopulating ability is reduced in mobilized blood.

Evaluation of optimal survival of primitive progenitor cells (LTC-IC) from PBPC apheresis products after overnight storage

“…18,19 In this context, primitive progenitors become more and more important because there is evidence that higher numbers of primitive cells may result in an accelerated hematopoietic reconstitution. 7 Our data also suggest that PBSC collections from unrelated donors (which probably will be performed more frequently over the next few years) should be transported at 4°C. To date, recommendations in this respect by the World Marrow Donor Association only exist for the transportation of bone marrow.…”

“…Recent animal data suggest that primitive progenitor cells are not only important for long-term engraftment but also contribute significantly to the early phase of hematopoietic engraftment after myeloablative therapy. 6,7 Moreover, transplantation of higher numbers of rhodamine-negative hematopoietic stem cells has resulted in an accelerated reconstitution. 7 These animal data seem to be relevant also in humans.…”

“…6,7 Moreover, transplantation of higher numbers of rhodamine-negative hematopoietic stem cells has resulted in an accelerated reconstitution. 7 These animal data seem to be relevant also in humans. When patients with multiple myeloma or breast cancer were transplanted with only a small subpopulation of CD34 + cells, that is highly enriched for primitive stem cells (ie CD34 + Thy1 + ), a rapid hematologic engraftment of all lineages occurred.…”

Survivin, a cancer target with an emerging role in normal adult tissues

“…These data suggest that prolonged or intensified antisurvivin therapy may have the potential to affect primitive hematopoietic cells. Because only hematopoietic stem cells support hematopoiesis, not progenitor cells (105,106), evaluation of the in vivo function of hematopoietic stem cells treated with antisurvivin therapy using long-term repopulating assays will be required to provide accurate information on primitive hematopoietic cell toxicity.…”

Clinical application of hematopoietic progenitor cell expansion: current status and future prospects

“…2 If successful, this would improve both early and late engraftments as HSCs, when given in sufficient quantity, contribute to both short-and long-term engraftments in mice. [102][103][104] This concept recently was proven in clinical trials involving high-speed sorting and transplantation of cells defined by a primitive hematopoietic phenotype. 105,106 Resources should be allocated towards the development of in vitro systems designed to expand LTRC.…”