Abstract
The inflamed bone marrow niche shortly after total body irradiation (TBI) is known to contribute to loss of hematopoietic stem cells in terms of their number and function. In this study, autologous bone marrow transfer (AL-BMT) was evaluated as a strategy for mitigating hematopoietic form of the acute radiation syndrome by timing the collection phase (2 h after irradiation) and reinfusion (24 h after irradiation) using mice as a model system. Collection of bone marrow (BM) cells (0.5 × 106 total marrow cells) 2 h after lethal TBI rescued different subclasses of hematopoietic stem and progenitor cells (HSPCs) from the detrimental inflammatory and damaging milieu in vivo. Cryopreservation of collected graft and its reinfusion 24 h after TBI significantly rescued mice from lethal effects of irradiation (65% survival against 0% in TBI group on day 30th) and hematopoietic depression. Transient hypometabolic state (HMS) induced 2 h after TBI effectively preserved the functional status of HSPCs and improved hematopoietic recovery even when BM was collected 8 h after TBI. Homing studies suggested that AL-BMT yielded similar percentages for different subsets of HSPCs when compared to syngeneic bone marrow transfer. The results suggest that the timing of collection, and reinfusion of graft is crucial for the success of AL-BMT.
Highlights
Matched allogenic bone marrow transfer (AG-bone marrow transplantation (BMT)) has long been established and used for treating radiation-induced hematopoietic depression [1]
Victims exposed to lower doses (
The AL-BMT of aspirated BM reinfused 24 h after TBI resulted in a survival advantage (16%) in comparison to the 0 survival observed in the TBI + HMS + Surg group (Figure 2)
Summary
Matched allogenic bone marrow transfer (AG-BMT) has long been established and used for treating radiation-induced hematopoietic depression [1]. Non-human primates (NHPs), and humans have reported that if a sufficient number of HSCs could be protected (by shielding the femur), it is possible to ameliorate the myeloablative effects of chemotherapy or radiation [5,6,7]. These studies prompted researchers to explore the efficiency of AL-BMT in the management of radiation-induced BM aplasia. In addition to its application in high-dose exposure patients, AL-BMT may be effective in enhancing hematopoietic recovery against moderate to sublethal radiation doses, where AG-BMT is not desired
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