• This record comes from PubMed

Second bone marrow transplantation into regenerating hematopoiesis enhances reconstitution of immune system

. 2024 ; 15 () : 1405210. [epub] 20240614

Language English Country Switzerland Media electronic-ecollection

Document type Journal Article

In bone marrow transplantation (BMT), hematopoiesis-reconstituting cells are introduced following myeloablative treatment, which eradicates existing hematopoietic cells and disrupts stroma within the hematopoietic tissue. Both hematopoietic cells and stroma then undergo regeneration. Our study compares the outcomes of a second BMT administered to mice shortly after myeloablative treatment and the first BMT, with those of a second BMT administered to mice experiencing robust hematopoietic regeneration after the initial transplant. We evaluated the efficacy of the second BMT in terms of engraftment efficiency, types of generated blood cells, and longevity of function. Our findings show that regenerating hematopoiesis readily accommodates newly transplanted stem cells, including those endowed with a robust capacity for generating B and T cells. Importantly, our investigation uncovered a window for preferential engraftment of transplanted stem cells coinciding with the resumption of blood cell production. Repeated BMT could intensify hematopoiesis reconstitution and enable therapeutic administration of genetically modified autologous stem cells.

See more in PubMed

Brecher G, Cronkite EP. Post-radiation parabiosis and survival in rats. Proc Soc Exp Biol Med. (1951) 77:292–4. doi: 10.3181/00379727-77-18754 PubMed DOI

Ford CE, Hamerton JL, Barnes DW, Loutit JF. Cytological identification of radiation-chimaeras. Nature. (1956) 177:452–4. doi: 10.1038/177452a0 PubMed DOI

Till JE, McCulloch EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. (1961) 14:213–22. doi: 10.2307/3570892 PubMed DOI

Becker AJ, Mcculloch EA, Simin0vitch L, Till JE. The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony-forming cells of mice(1965) (Accessed July 27, 2023). PubMed

Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. (2006) 354:1813–26. doi: 10.1056/NEJMRA052638 PubMed DOI

Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med. (2007) 357:1472–5. doi: 10.1056/NEJMP078166 PubMed DOI

Henig I, Zuckerman T. Hematopoietic stem cell transplantation-50 years of evolution and future perspectives. Rambam Maimonides Med J. (2014) 5:e0028. doi: 10.5041/RMMJ.10162 PubMed DOI PMC

Morita Y, Ema H, Nakauchi H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med. (2010) 207:1173–82. doi: 10.1084/jem.20091318 PubMed DOI PMC

Ema H, Morita Y, Suda T. Heterogeneity and hierarchy of hematopoietic stem cells. Exp Hematol. (2014) 42:74–82.e2. doi: 10.1016/j.exphem.2013.11.004 PubMed DOI

Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph KL, et al. . Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell. (2013) 154:1112–26. doi: 10.1016/j.cell.2013.08.007 PubMed DOI

Yamamoto R, Wilkinson AC, Ooehara J, Lan X, Lai CY, Nakauchi Y, et al. . Large-scale clonal analysis resolves aging of the mouse hematopoietic stem cell compartment. Cell Stem Cell. (2018) 22:600–607.e4. doi: 10.1016/j.stem.2018.03.013 PubMed DOI PMC

Faltusová K, Chen C-L, Heizer T, Báječný M, Szikszai K, Páral P, et al. . Altered erythro-myeloid progenitor cells are highly expanded in intensively regenerating hematopoiesis. Front Cell Dev Biol. (2020) 8:98. doi: 10.3389/FCELL.2020.00098 PubMed DOI PMC

Nishi K, Sakamaki T, Sadaoka K, Fujii M, Takaori-Kondo A, Chen JY, et al. . Identification of the minimum requirements for successful haematopoietic stem cell transplantation. Br J Haematol. (2022) 196:711–23. doi: 10.1111/BJH.17867 PubMed DOI PMC

Biasco L, Pellin D, Scala S, Di SC, Naldini L, Aiuti A. In vivo tracking of human hematopoiesis reveals patterns of clonal dynamics during early and steady-state reconstitution phases. Cell Stem Cell. (2016) 19:107–19. doi: 10.1016/j.stem.2016.04.016 PubMed DOI PMC

Dykstra B, Kent D, Bowie M, McCaffrey L, Hamilton M, Lyons K, et al. . Long-term propagation of distinct hematopoietic differentiation programs in vivo . Cell Stem Cell. (2007) 1:218–29. doi: 10.1016/j.stem.2007.05.015 PubMed DOI

Wilson NK, Kent DG, Buettner F, Shehata M, Macaulay IC, Calero-Nieto FJ, et al. . Combined single-cell functional and gene expression analysis resolves heterogeneity within stem cell populations. Cell Stem Cell. (2015) 16:712–24. doi: 10.1016/j.stem.2015.04.004 PubMed DOI PMC

Adolfsson J, Månsson R, Buza-Vidas N, Hultquist A, Liuba K, Jensen CT, et al. . Identification of flt3+ Lympho-myeloid stem cells lacking erythro-megakaryocytic potential. Cell. (2005) 121:295–306. doi: 10.1016/j.cell.2005.02.013 PubMed DOI

Faltusová K, Báječný M, Heizer T, Páral P, Nečas E. T-lymphopoiesis is severely compromised in ubiquitin-green fluorescent protein transgenic mice. Folia Biol (Praha). (2020) 66:47–59. doi: 10.14712/fb2020066020047 PubMed DOI

Mendelson A, Frenette PS. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med. (2014) 20:833. doi: 10.1038/NM.3647 PubMed DOI PMC

Pinho S, Frenette PS. Haematopoietic stem cell activity and interactions with the niche. Nat Rev Mol Cell Biol. (2019) 20:303–20. doi: 10.1038/S41580-019-0103-9 PubMed DOI PMC

Colvin GA, Lambert J-F, Abedi M, Hsieh C-C, Carlson JE, Stewart FM, et al. . Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology. Leukemia. (2004) 18:575–83. doi: 10.1038/sj.leu.2403268 PubMed DOI

Forgacova K, Savvulidi F, Sefc L, Linhartova J, Necas E. All hematopoietic stem cells engraft in submyeloablatively irradiated mice. Biol Blood Marrow Transplant. (2013) 19:713–9. doi: 10.1016/j.bbmt.2013.02.012 PubMed DOI

Lu R, Czechowicz A, Seita J, Jiang D, Weissman IL. Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo . Proc Natl Acad Sci U.S.A. (2019) 116:1447–56. doi: 10.1073/pnas.1801480116 PubMed DOI PMC

Slayton WB, Li X-M, Butler J, Guthrie SM, Jorgensen ML, Wingard JR, et al. . The role of the donor in the repair of the marrow vascular niche following hematopoietic stem cell transplant. Stem Cells. (2007) 25:2945–55. doi: 10.1634/stemcells.2007-0158 PubMed DOI

Li XM, Hu Z, Jorgenson ML, Wingard JR, Slayton WB. Bone marrow sinusoidal endothelial cells undergo nonapoptotic cell death and are replaced by proliferating sinusoidal cells in situ to maintain the vascular niche following lethal irradiation. Exp Hematol. (2008) 36:1143–56. doi: 10.1016/j.exphem.2008.06.009 PubMed DOI

Dominici M, Rasini V, Bussolari R, Chen X, Hofmann TJ, Spano C, et al. . Restoration and reversible expansion of the osteoblastic hematopoietic stem cell niche after marrow radioablation. Blood. (2009) 114:2333–43. doi: 10.1182/blood-2008-10-183459 PubMed DOI PMC

Zhao M, Perry JM, Marshall H, Venkatraman A, Qian P, He XC, et al. . Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells. Nat Med. (2014) 20:1321–6. doi: 10.1038/NM.3706 PubMed DOI

Bowers E, Slaughter A, Frenette PS, Kuick R, Pello OM, Lucas D. Granulocyte-derived TNFα promotes vascular and hematopoietic regeneration in the bone marrow. Nat Med. (2018) 24:95. doi: 10.1038/NM.4448 PubMed DOI PMC

Golan K, Singh AK, Kollet O, Bertagna M, Althoff MJ, Khatib-Massalha E, et al. . Hematopoiesis and Stem Cells: Bone marrow regeneration requires mitochondrial transfer from donor Cx43-expressing hematopoietic progenitors to stroma. Blood. (2020) 136:2607. doi: 10.1182/BLOOD.2020005399 PubMed DOI PMC

Shen H, Yu H, Liang PH, Cheng H, XuFeng R, Yuan Y, et al. . An acute negative bystander effect of γ-irradiated recipients on transplanted hematopoietic stem cells. Blood. (2012) 119:3629–37. doi: 10.1182/BLOOD-2011-08-373621 PubMed DOI PMC

Ratajczak MZ, Adamiak M, Deptała A, Domagała-Kulawik J, Ratajczak J, Kucia M. Myeloablative conditioning for transplantation induces state of sterile inflammation in the bone marrow: implications for optimizing homing and engraftment of hematopoietic stem cells. Antioxid Redox Signal. (2022) 37:1254–65. doi: 10.1089/ARS.2022.0042 PubMed DOI PMC

Báječný M, Chen C-L, Faltusová K, Heizer T, Szikszai K, Páral P, et al. . Hematopoiesis remains permissive to bone marrow transplantation after expansion of progenitors and resumption of blood cell production. Front Cell Dev Biol. (2021) 0:660617. doi: 10.3389/FCELL.2021.660617 PubMed DOI PMC

Faltusová K, Szikszai K, Molík M, Linhartová J, Páral P, Šefc L, et al. . Stem cell defect in ubiquitin-green fluorescent protein mice facilitates engraftment of lymphoid-primed hematopoietic stem cells. Stem Cells. (2018) 36:1237–48. doi: 10.1002/stem.2828 PubMed DOI

Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. (2005) 121:1109–21. doi: 10.1016/j.cell.2005.05.026 PubMed DOI

Hooper AT, Butler JM, Nolan DJ, Kranz A, Iida K, Kobayashi M, et al. . Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Cell Stem Cell. (2009) 4:263–74. doi: 10.1016/j.stem.2009.01.006 PubMed DOI PMC

Kaur S, Raggatt LJ, Millard SM, Wu AC, Batoon L, Jacobsen RN, et al. . Self-repopulating recipient bone marrow resident macrophages promote long-term hematopoietic stem cell engraftment. Blood. (2018) 132:735–49. doi: 10.1182/blood-2018-01-829663 PubMed DOI

Ju W, Lu W, Ding L, Bao Y, Hong F, Chen Y, et al. . PEDF promotes the repair of bone marrow endothelial cell injury and accelerates hematopoietic reconstruction after bone marrow transplantation. J BioMed Sci. (2020) 27:91. doi: 10.1186/s12929-020-00685-4 PubMed DOI PMC

Chalot M, Barroca V, Devanand S, Hoffschir F, Romeo P-H, Ephanie S, et al. . Deleterious effect of bone marrow-resident macrophages on hematopoietic stem cells in response to total body irradiation. Blood Adv. (2022) 6:1766–79. doi: 10.1182/bloodadvances.2021005983 PubMed DOI PMC

Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, et al. . Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature. (2019) 571:117–21. doi: 10.1038/s41586-019-1244-x PubMed DOI PMC

Che JLC, Bode D, Kucinski I, Cull AH, Bain F, Becker HJ, et al. . Identification and characterization of in vitro expanded hematopoietic stem cells. EMBO Rep. (2022) 23:e55502. doi: 10.15252/EMBR.202255502 PubMed DOI PMC

Igarashi KJ, Kucinski I, Yi Chan Y, Tan TK, Khoo HM, Kealy D, et al. . Physioxia improves the selectivity of hematopoietic stem cell expansion cultures. Blood Adv. (2023) 7:3366–77. doi: 10.1182/BLOODADVANCES.2023009668 PubMed DOI PMC

Cohen S, Roy J, Lachance S, Delisle JS, Marinier A, Busque L, et al. . Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1–2 safety and feasibility study. Lancet Haematol. (2020) 7:e134–45. doi: 10.1016/S2352-3026(19)30202-9 PubMed DOI

Sakurai M, Ishitsuka K, Ito R, Wilkinson AC, Kimura T, Mizutani E, et al. . Chemically defined cytokine-free expansion of human haematopoietic stem cells. Nature. (2023) 615:127. doi: 10.1038/s41586-023-05739-9 PubMed DOI

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...