Journal of Materials Chemistry B
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2024
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IF 6.1
Jing Hong,Zhanchi Zhu,Leisha Cui,Zhaojun Wang,Ying Hao,Xiaopeng Tian,Guosheng Cheng
Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin–hyaluronic acid (Gel–HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel–HA hydrogel surrounding the GF. The “soft” Gel–HA hydrogel and “stiff” GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel–HA/GF scaffold proliferated well and retained the CD34+CD38− immunophenotype and pluripotency, suggesting that the Gel–HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.
研究领域:
生物材料
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组织工程
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干细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Teng Wang,Weilin Liu,Chunyi Lyu,Yunxiao Luo,Xinyu Tang,Chen Han,Ruirong Xu
Ethnopharmacological relevance Realgar is an arsenic-containing mineral medicine and a key component of Realgar-Indigo naturalis formula, an oral traditional Chinese medicine preparation clinically used in China for acute promyelocytic leukemia (APL), a biologically distinct subtype of acute myeloid leukemia (AML). Realgar Transforming Solution (RTS) is a microbially processed realgar preparation. Its activity in AML stem cell-like contexts outside APL remains insufficiently defined, particularly in cell-line-derived CD34 + CD38 − LSC-like models. Aim of the study: To evaluate whether RTS suppresses stemness-associated phenotypic features in KG-1a-derived CD34 + CD38 − LSC-like cells and to explore its association with endoplasmic reticulum stress (ERS), mitochondrial injury, and mitophagy-related alterations. Materials and methods CD34 + CD38 − LSC-like cells were enriched from KG-1a cells and used as a cell-line-derived in vitro model. Cell viability, apoptosis, cell cycle, CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression were assessed after RTS treatment. RNA sequencing, Ca 2+ measurement, ROS detection, mitochondrial membrane potential assay, MDC staining, western blotting, RT-qPCR, immunofluorescence, and transmission electron microscopy were performed. 4-phenylbutyric acid and Mdivi-1 were used as pharmacological rescue agents. Results RTS reduced the CD34 + CD38 − fraction, colony formation, and TIM3/ HAVCR2 expression, while inducing apoptosis in KG-1a-derived LSC-like cells. Transcriptomics implicated ER protein processing, unfolded protein response, apoptosis, autophagy, and mitophagy-related pathways. RTS increased Ca 2+ levels, ROS accumulation, mitochondrial depolarization, PERK-eIF2α-ATF4-CHOP signaling, and PINK1/Parkin-associated mitophagy-like marker changes. 4-phenylbutyric acid and Mdivi-1 partially rescued RTS-impaired LSC-like phenotypic features, supporting pathway involvement. Conclusions RTS suppressed stemness-associated phenotypic features in a KG-1a-derived CD34 + CD38 − LSC-like model. These effects were associated with ERS, mitochondrial injury, and PINK1/Parkin-related mitophagy-like alterations.
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DOI
PubMed
高影响因子
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