In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such an endothelial compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays. (c) 2022 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
机构:
Univ Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Assis-Ribas, Thais
;
Forni, Maria Fernanda
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Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Forni, Maria Fernanda
;
Brochado Winnischofer, Sheila Maria
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Univ Fed Parana, Dept Bioquim & Biol Mol, BR-81531990 Curitiba, Parana, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Brochado Winnischofer, Sheila Maria
;
Sogayar, Mari Cleide
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Univ Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Sogayar, Mari Cleide
;
Trombetta-Lima, Marina
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Univ Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Univ Sao Paulo, NUCEL NETCEM Fac Med, Rua Pangare,100 Cidade Univ, BR-05360120 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
机构:
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Au, Patrick
;
Tam, Joshua
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Tam, Joshua
;
Fukumura, Dai
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Fukumura, Dai
;
Jain, Rakesh K.
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h-index: 0
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Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
机构:
Univ Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Assis-Ribas, Thais
;
Forni, Maria Fernanda
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Forni, Maria Fernanda
;
Brochado Winnischofer, Sheila Maria
论文数: 0引用数: 0
h-index: 0
机构:
Univ Fed Parana, Dept Bioquim & Biol Mol, BR-81531990 Curitiba, Parana, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Brochado Winnischofer, Sheila Maria
;
Sogayar, Mari Cleide
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Sogayar, Mari Cleide
;
Trombetta-Lima, Marina
论文数: 0引用数: 0
h-index: 0
机构:
Univ Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
Univ Sao Paulo, NUCEL NETCEM Fac Med, Rua Pangare,100 Cidade Univ, BR-05360120 Sao Paulo, SP, BrazilUniv Sao Paulo, NUCEL NETCEM Fac Med, Dept Clin Med, BR-05360120 Sao Paulo, SP, Brazil
机构:
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Au, Patrick
;
Tam, Joshua
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Tam, Joshua
;
Fukumura, Dai
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA
Fukumura, Dai
;
Jain, Rakesh K.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USAHarvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA