Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches.
García-García A., Klein T., Born G., Hilpert M., Scherberich A., Lengerke C.
Prospective Study, published in Proc Natl Acad Sci U S A (2021) — summary generated from the PubMed abstract.
Early human evidence such as case series or small samples is exploring possible benefits.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Prospective Study
- Journal
- Proc Natl Acad Sci U S A (2021)
- Country
- United States
- Reported sample size
- —
- Source database
- PubMed
- PMID
- 34580200
- PMCID
- PMC8501773
- DOI
- 10.1073/pnas.2114227118
- Citations
- 32
Abstract (original English)
Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone marrow. Our group previously reported that human osteoblastic BM niches (O-N), engineered by culturing mesenchymal stromal cells within three-dimensional (3D) porous scaffolds under perfusion flow in a bioreactor system, are capable of maintaining, expanding, and functionally regulating healthy human cord blood-derived HSPCs. Here, we first demonstrate that this 3D O-N can sustain malignant CD34 + cells from acute myeloid leukemia (AML) and myeloproliferative neoplasm patients for up to 3 wk. Human malignant cells distributed in the bioreactor system mimicking the spatial distribution found in native BM tissue, where most HSPCs remain linked to the niches and mature cells are released to the circulation. Using human adipose tissue-derived stromal vascular fraction cells, we then generated a stromal-vascular niche and demonstrated that O-N and stromal-vascular niche differentially regulate leukemic UCSD-AML1 cell expansion, immunophenotype, and response to chemotherapy. The developed sy
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
Evidence level
Early human evidence such as case series or small samples is exploring possible benefits.
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