Survival of irradiated recipient mice after transplantation of bone marrow from young, old and “early aging” mice

Abstract

Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16–18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best.

Mobilization‐based transplantation of young‐donor hematopoietic stem cells extends lifespan in mice

“…We therefore reasoned that an effect on lifespan shown in females would be a more robust finding than one shown in males. Furthermore, our shorter host lifespans (Guest et al, 2015) and increased myeloid lineage skewing due to "defective" HSCs (Lee, Yoon, Choi, & Jung, 2019).…”

“…Importantly, this study includes the first successful HSCT, in which severe adverse effects such as rapid declines in body weight (Duran‐Struuck & Dysko, ; Iestra, Fibbe, Zwinderman, Staveren, & Kromhout, ) and reduced survival (Guest, Ilic, Scrable, & Sell, ) were not observed. Recipients undergoing this mobilization‐based HSCT procedure required no additional care—e.g., antibiotics, acidic water, or frequent cage changes—to prevent HSCT‐related mortality (Duran‐Struuck & Dysko, ).…”

“…However, the HSCT protocol requires harvesting HSCs at a ratio of 2:1 (donors to recipients) over the 8 transplantation cycles for each recipient, totaling 16 donor mice per recipient, which was not possible due to strict limitations in the number of aged mice available from the NIA resource (20 animals/ month). We do not believe that the study is compromised by this limitation in aged donor HSC availability, since there are clear differences between transplanting young versus aged HSCs, including shorter host lifespans (Guest et al, ) and increased myeloid lineage skewing due to “defective” HSCs (Lee, Yoon, Choi, & Jung, ).…”

Inducible disruption of the c-myb gene allows allogeneic bone marrow transplantation without irradiation

“…4a, b). In comparison, in models of allogeneic BM transplantation using irradiation survival rates of 80–90% have been described (Cui et al, 2002; Guest et al, 2015). The relative percentage of chimerism critically depends on the extend of BM depletion before transplantation.…”

Animal Welfare in Radiation Research: The Importance of Animal Monitoring System

“…The main challenges in radiation research persist in terms of reproducibility and comparability, as there is a significant disparity in the main parameters used in BMT models, such as the murine strain and dose employed, which could be single or fractionated, and the time between irradiation and injection of hematopoietic cells, which could range from to 1 to 24 h [46][47][48]. In addition, the number of hematopoietic cells injected could vary from 5 × 10 5 to 7.5 × 10 6 , as well as the site of injection that could be retro-orbital, or intrafemoral, with the most used being the caudal vein [46][47][48][49][50].…”