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Challenges and innovations in hematopoietic stem cell transplantation: exploring bone marrow niches and new model systems

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Hematopoietic stem cell transplantation (HSCT) remains an indispensable therapeutic strategy for various hematological diseases. This review discusses the pivotal role of bone marrow (BM) niches in influencing the efficacy of HSCT and evaluates the current animal models, emphasizing their limitations and the need for alternative models. Traditional animal models, mainly murine xenograft, have provided significant insights, but due to species-specific differences, are often constrained from accurately mimicking human physiological responses. These limitations highlight the importance of developing alternative models that can more realistically replicate human hematopoiesis. Emerging models that include BM organoids and BM-on-a-chip microfluidic systems promise enhanced understanding of HSCT dynamics. These models aim to provide more accurate simulations of the human BM microenvironment, potentially leading to improved preclinical assessments and therapeutic outcomes. This review highlights the complexities of the BM niche, discusses the limitations of current models, and suggests directions for future research using advanced model systems.

Abstract

Hematopoietic stem cell transplantation (HSCT) remains an indispensable therapeutic strategy for various hematological diseases. This review discusses the pivotal role of bone marrow (BM) niches in influencing the efficacy of HSCT and evaluates the current animal models, emphasizing their limitations and the need for alternative models. Traditional animal models, mainly murine xenograft, have provided significant insights, but due to species-specific differences, are often constrained from accurately mimicking human physiological responses. These limitations highlight the importance of developing alternative models that can more realistically replicate human hematopoiesis. Emerging models that include BM organoids and BM-on-a-chip microfluidic systems promise enhanced understanding of HSCT dynamics. These models aim to provide more accurate simulations of the human BM microenvironment, potentially leading to improved preclinical assessments and therapeutic outcomes. This review highlights the complexities of the BM niche, discusses the limitations of current models, and suggests directions for future research using advanced model systems.

참고문헌 (107)

  1. Philippidis A, "CASGEVY makes history as FDA approves first CRISPR", Cas9 genome edited therapy, 2024, pp.35, 1~4
  2. Parums DV, "First regulatory approvals for CRISPRCas9therapeutic gene editing for sickle cell disease and transfusion-dependent -thalassemia", Med Sci Monit, 30, pp.e944204~ (2024)
  3. Philippidis A, "Graphite bio pauses lead gene editing program in sickle cell disease", Hum Gene Ther, 34, pp.90~93 (2023)
  4. Maganti HB, "Persistence of CRISPR", Cas9 gene edited hematopoietic stem cells following transplantation : a systematic review and meta-analysis of preclinical studies, 2021, pp.10, 996~1007
  5. Radtke S, "Mouse models in hematopoietic stem cell gene therapy and genome editing", Biochem Pharmacol, 174, pp.113692~ (2020)
  6. Uchida N, "Preclinical evaluation for engraftment of CD34+ cells gene-edited at the sickle cell disease locus in xenograft mouse and non-human primate models", Cell Rep Med, 2, pp.100247~ (2021)
  7. Schofield R, "The relationship between the spleen colony-forming cell and the haemopoietic stem cell", Blood cells, 4, pp.7~25 (1978)
  8. Nilsson SK, "Hemopoietic stem cell engraftment", Exp Hematol, 34, pp.123~129 (2006)
  9. Ratajczak MZ, "Emerging strategies to enhance homing and engraftment of hematopoietic stem cells", Stem Cell Rev Rep, 12, pp.121~128 (2016)
  10. Lapidot T, "The brain-bone-blood triad : traffic lights for stem-cell homing and mobilization", Hematology Am Soc Hematol Educ Program, 2010, pp.1~6 (2010)
  11. Aiuti A, "The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood", J Exp Med, 185, pp.111~120 (1997)
  12. Imai Y, "Essential roles of VLA-4 in the hematopoietic system", Int J Hematol, 91, pp.569~575 (2010)
  13. Krause DS, "Selectins and their ligands are required for homing and engraftment of BCR-ABL1+leukemic stem cells in the bone marrow niche", Blood, 123, pp.1361~1371 (2014)
  14. Xia L, "Surface fucosylation of human cord blood cells augments binding to P-selectin and E-selectin and enhances engraftment in bone marrow", Blood, 104, pp.3091~3096 (2004)
  15. Rademakers T, "Hematopoietic stem and progenitor cells use podosomes to transcellularly cross the bone marrow endothelium", Haematologica, 105, pp.2746~2756 (2020)
  16. Mitroulis I, "Regulation of the bone marrow niche by inflammation", Front Immunol, 11, pp.1540~ (2020)
  17. Nilsson SK, "Potential and distribution of transplanted hematopoietic stem cells in a nonablated mouse model", Blood, 89, pp.4013~4020 (1997)
  18. Al-Amoodi AS, "Refining the migration and engraftment of short-term and longterm HSCs by enhancing homing-specific adhesion mechanisms", Blood Adv, 6, pp.4373~4391 (2022)
  19. Nilsson SK, "Spatial localization of transplanted hemopoietic stem cells : inferences for the localization of stem cell niches", Blood, 97, pp.2293~2299 (2001)
  20. Birbrair A, "Niche heterogeneity in the bone marrow", Ann N Y Acad Sci, 1370, pp.82~96 (2016)
  21. Morrison SJ, "The bone marrow niche for haematopoietic stem cells", Nature, 505, pp.327~334 (2014)
  22. Kopp HG, "The bone marrow vascular niche : home of HSC differentiation and mobilization", Physiology, 20, pp.349~356 (2005)
  23. Asada N, "Differential cytokine contributions of perivascular haematopoietic stem cell niches", Nat Cell Biol, 19, pp.214~223 (2017)
  24. Sugiyama T, "Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches", Immunity, 25, pp.977~988 (2006)
  25. Niswander LM, "SDF-1 dynamically mediates megakaryocyte niche occupancy and thrombopoiesis at steady state and following radiation injury", Blood, 124, pp.277~286 (2014)
  26. Petit I, "The SDF-1-CXCR4 signaling pathway : a molecular hub modulating neo-angiogenesis", Trends Immunol, 28, pp.299~307 (2007)
  27. Heino TJ, "Bone marrow niche : role of different cells in bone metastasis", Curr Mol Bio Rep, 4, pp.80~87 (2018)
  28. Arai F, "Tie2", angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche, 2004, pp.118, 149~161
  29. Robles H, "Characterization of the bone marrow adipocyte niche with three-dimensional electron microscopy", Bone, 118, pp.89~98 (2019)
  30. Tratwal J, "Bone marrow adiposity and the hematopoietic niche : a historical perspective of reciprocity, heterogeneity, and lineage commitment", Best Pract Res Clin Endocrinol Metab, 35, pp.101564~ (2021)
  31. Chow A, "Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche", J Exp Med, 208, pp.261~271 (2011)
  32. Sapoznikov A, "Perivascular clusters of dendritic cells provide critical survival signals to B cells in bone marrow niches", Nat Immunol, 9, pp.388~395 (2008)
  33. Semerad CL, "G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow", Blood, 106, pp.3020~3027 (2005)
  34. Yoshihara H, "Thrombopoietin", MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche, 2007, pp.1, 685~697
  35. Nilsson SK, "Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells", Blood, 106, pp.1232~1239 (2005)
  36. Goldman DC, "BMP4 regulates the hematopoietic stem cell niche", Blood, 114, pp.4393~4401 (2009)
  37. Varnum-Finney B, "Notch2 governs the rate of generation of mouse long-and short-term repopulating stem cells", J Clin Invest, 121, pp.1207~1216 (2011)
  38. Hosokawa K, "Cadherinbased adhesion is a potential target for niche manipulation to protect hematopoietic stem cells in adult bone marrow", Cell Stem Cell, 6, pp.194~198 (2010)
  39. Sims NA, "Bone remodeling : multiple cellular interactions required for coupling of bone formation and resorption", Semin Cell Dev Biol, 19, pp.444~451 (2008)
  40. Winkler IG, "Bone marrow macrophages maintain hematopoietic stem cell(HSC)niches and their depletion mobilizes HSCs", Blood, 116, pp.4815~4828 (2010)
  41. Mohamad SF, "Osteomacs promote maintenance of murine hematopoiesis through megakaryocyte-induced upregulation of Embigin and CD166", Stem Cell Reports, 19, pp.486~500 (2024)
  42. Bruns I, "Megakaryocytes regulate hematopoietic stem cell quiescence via CXCL4secretion", Nat Med, 20, pp.1315~1320 (2014)
  43. Yamazaki S, "Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche", Cell, 147, pp.1146~1158 (2011)
  44. Zhang P, "The physical microenvironment of hematopoietic stem cells and its emerging roles in engineering applications", Stem Cell Res Ther, 10, pp.1~13 (2019)
  45. Bhatia M, "Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice", Proc Natl Acad Sci U S A, 94, pp.5320~5325 (1997)
  46. Goyama S, "Xenograft models for normal and malignant stem cells", Blood, 125, pp.2630~2640 (2015)
  47. Kohnken R, "Overview of the use of murine models in leukemia and lymphoma research", Front Oncol, 7, pp.22~ (2017)
  48. Ito M, "NOD", SCID, Blood, pp.2002, 100[DOI]
  49. Ishikawa F, "Development of functional human blood and immune systems in NOD", SCID, Blood, pp.2005, 106[DOI]
  50. Audigé A, "Long-term leukocyte reconstitution in NSG mice transplanted with human cord blood hematopoietic stem and progenitor cells", BMC immunol, 18, pp.28~ (2017)
  51. Civini S, "Leukemia cells induce changes in human bone marrow stromal cells", J Transl Med, 11, pp.298~ (2013)
  52. Hanoun M, "Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche", Cell Stem Cell, 15, pp.365~375 (2014)
  53. Sarry JE, "Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD", SCID, J Clin Invest, pp.2011, 121[DOI]
  54. Zhang Y, "Engraftment of chronic myelomonocytic leukemia cells in immunocompromised mice supports disease dependency on cytokines", Blood Adv, 1, pp.972~979 (2017)
  55. Wunderlich M, "AML xenograft efficiency is significantly improved in NOD", SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3, 2010, pp.24, 1785~1788
  56. Reinisch A, "A humanized bone marrow ossicle xenotransplantation model enables improved engraftment of healthy and leukemic human hematopoietic cells", Nat Med, 22, pp.812~821 (2016)
  57. Medyouf H, "Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit", Cell Stem Cell, 14, pp.824~837 (2014)
  58. Wege A, "Functional and phenotypic characterization of the humanized BLT mouse model", Curr Top Microbiol Immunol, 324, pp.149~165 (2008)
  59. Marsden MD, "HIV latency in the humanized BLT mouse", J Virol, 86, pp.339~347 (2012)
  60. Wang LX, "Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection", Proc Natl Acad Sci U S A, 111, pp.3146~3151 (2014)
  61. Brainard DM, "Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virusinfected humanized BLT mice", J Virol, 83, pp.7305~7321 (2009)
  62. Lee BC, "A RUNX1-FPDMM rhesus macaque model reproduces the human phenotype and predicts challenges to curative gene therapies", Blood, 141, pp.231~237 (2023)
  63. Lee BC, "Impact of CRISPR", HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques, 2024, pp.31, 455~466
  64. Wu C, "Clonal expansion and compartmentalized maintenance of rhesus macaque NK cell subsets", Sci Immunol, pp.9781~ (2018)
  65. Clevers H, "Modeling development and disease with organoids", Cell, 165, pp.1586~1597 (2016)
  66. Kim J, "Human organoids : model systems for human biology and medicine", Nat Rev Mol Cell Biol, 21, pp.571~584 (2020)
  67. Sasai Y, "Cytosystems dynamics in self-organization of tissue architecture", Nature, 493, pp.318~326 (2013)
  68. Lancaster MA, "Disease modelling in human organoids", Dis Model Mech, 12, pp.039347~ (2019)
  69. Mantalaris A, "Engineering a human bone marrow model : a case study on ex vivo erythropoiesis", Biotechnol Prog, 14, pp.126~133 (1998)
  70. Olijnik AA, "Generating human bone marrow organoids for disease modeling and drug discovery", Nat Protoc, 19, pp.2117~2146 (2024)
  71. Khan AO, "Human bone marrow organoids for disease modeling, discovery, and validation of therapeutic targets in hematologic malignancies", Cancer Discov, 13, pp.364~385 (2023)
  72. Giger S, "Microarrayed human bone marrow organoids for modeling blood stem cell dynamics", APL Bioeng, 6, pp.036101~ (2022)
  73. Pievani A, "Human umbilical cord blood-borne fibroblasts contain marrow niche precursors that form a bone", marrow organoid in vivo, 2017, pp.144, 1035~1044
  74. Vallmajo-Martin Q, "PEG", HA hybrid hydrogels for biologically and mechanically tailorable bone marrow organoids, 2020, pp.30, 1910282~
  75. Frenz-Wiessner S, "Generation of complex bone marrow organoids from human induced pluripotent stem cells", Nat Methods, 21, pp.868~881 (2024)
  76. Boulais PE, "Making sense of hematopoietic stem cell niches", Blood, 125, pp.2621~2629 (2015)
  77. Shono Y, "Bone marrow graft-versus-host disease : early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation", Blood, 115, pp.5401~5411 (2010)
  78. Doan P, "The vascular niche : home for normal and malignant hematopoietic stem cells", Leukemia, 26, pp.54~62 (2012)
  79. Kfoury Y, "Mesenchymal cell contributions to the stem cell niche", Cell Stem Cell, 16, pp.239~253 (2015)
  80. Lee-Thedieck C, "The extracellular matrix of hematopoietic stem cell niches", Adv Drug Deliv Rev, 181, pp.114069~ (2022)
  81. Zhang X, "Stiffness matters : a soft bone marrow organoid rejuvenates hematopoietic stem cells", Mechanobiol Med, 1, pp.100009~ (2023)
  82. de Janon A, "Three-dimensional human bone marrow organoids for the study and application of normal and abnormal hematoimmunopoiesis", J Immunol, 210, pp.895~904 (2023)
  83. Rashad HM, "Multiple Myeloma 3D model : a platform for testing drug effects on myeloma in conjunction with the bone marrow niche", Cancer Res, 83, pp.184~184 (2023)
  84. Ferreira MSV, "Cord blood-hematopoietic stem cell expansion in 3D fibrin scaffolds with stromal support", Biomaterials, 33, pp.6987~6997 (2012)
  85. Mortera-Blanco T, "Long-term cytokine-free expansion of cord blood mononuclear cells in three-dimensional scaffolds", Biomaterials, 32, pp.9263~9270 (2011)
  86. Cuddihy MJ, "Replication of bone marrow differentiation niche : comparative evaluation of different three-dimensional matrices", Small, 9, pp.1008~1015 (2013)
  87. Sacchetti B, "Selfrenewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment", Cell, 131, pp.324~336 (2007)
  88. Reinisch A, "Generation and use of a humanized bone-marrowossicle niche for hematopoietic xenotransplantation into mice", Nat Protoc, 12, pp.2169~2188 (2017)
  89. Pievani A, "Acute myeloid leukemia shapes the bone marrow stromal niche in vivo", Haematologica, 106, pp.865~870 (2021)
  90. Serafini M, "Establishment of bone marrow and hematopoietic niches in vivo by reversion of chondrocyte differentiation of human bone marrow stromal cells", Stem Cell Res, 12, pp.659~672 (2014)
  91. Demirci S, "Definitive hematopoietic stem", progenitor cells from human embryonic stem cells through serum, Stem Cell Res Ther, pp.2020, 11[DOI]
  92. Yi SA, "Bioengineering approaches for the advanced organoid research", Adv Mater, 33, pp.2007949~ (2021)
  93. Wimmer RA, "Generation of blood vessel organoids from human pluripotent stem cells", Nature Protoc, 14, pp.3082~3100 (2019)
  94. Wimmer RA, "Human blood vessel organoids as a model of diabetic vasculopathy", Nature, 565, pp.505~510 (2019)
  95. Arranz L, "Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms", Nature, 512, pp.78~81 (2014)
  96. Han J, "High-oxygen submersion fetal thymus organ cultures enable FOXN1-dependent and-independent support of T lymphopoiesis", Front Immunol, 12, pp.652665~ (2021)
  97. Ramos SA, "Generation of functional thymic organoids from human pluripotent stem cells", Stem Cell Reports, 18, pp.829~840 (2023)
  98. Zlotoff DA, "Hematopoietic progenitor migration to the adult thymus", Ann N Y Acad Sci, 1217, pp.122~138 (2011)
  99. Torisawa YS, "Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro", Nat Methods, 11, pp.663~669 (2014)
  100. Sieber S, "Bone marrowon-a-chip : long-term culture of human haematopoietic stem cells in a three-dimensional microfluidic environment", J Tissue Eng Regen Med, 12, pp.479~489 (2018)
  101. Aleman J, "Deconstructed microfluidic bone marrow on-a-chip to study normal and malignant hemopoietic cell-niche interactions", Small, 15, pp.1902971~ (2019)
  102. Glaser DE, "Organon-a-chip model of vascularized human bone marrow niches", Biomaterials, 280, pp.121245~ (2022)
  103. Chou DB, "On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology", Nat Biomed Eng, 4, pp.394~406 (2020)
  104. Park Y, "Trabecular bone organoid model for studying the regulation of localized bone remodeling", Sci Adv, 7, pp.6495~ (2021)
  105. Zhao D, "Bone organoids : recent advances and future challenges", Adv Healthc Mater, 13, pp.2302088~ (2024)
  106. Kanton S, "Human assembloids", Development, 149, pp.201120~ (2022)
  107. Cannon P, "Safe and effective in vivo targeting and gene editing in hematopoietic stem cells : strategies for accelerating development", Hum Gene Ther, 32, pp.31~42 (2021)

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