A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells

Xu, Yan; Shan, Wei; Li, Xia; Wang, Binsheng; Liu, Senquan; Wang, Yebo; Long, Yan; Tie, Ruxiu; Wang, Limengmeng; Cai, Shuyang; Zhang, Hao; Lin, Yaw Huei; Zhang, Mingming; Zheng, Weiyan; Luo, Yi; Yu, Xiaohong; Yee, Jiing‐Kuan; Ji, Junfeng; Huang, He

doi:10.1186/s13045-016-0326-6

Cited by 16 publications

(21 citation statements)

References 63 publications

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“…Therefore, future work should emphasize the mechanisms of the HSC niche during aging. Moreover, expanding long-term HSCs in vitro is still a challenge, and the findings of HSC aging could be applied to this challenge [143][144][145][146]. For example, some rejuvenation molecules might be added to expand HSCs.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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Hematopoietic stem cell (HSC) aging, which is accompanied by reduced self-renewal ability, impaired homing, myeloid-biased differentiation, and other defects in hematopoietic reconstitution function, is a hot topic in stem cell research. Although the number of HSCs increases with age in both mice and humans, the increase cannot compensate for the defects of aged HSCs. Many studies have been performed from various perspectives to illustrate the potential mechanisms of HSC aging; however, the detailed molecular mechanisms remain unclear, blocking further exploration of aged HSC rejuvenation. To determine how aged HSC defects occur, we provide an overview of differences in the hallmarks, signaling pathways, and epigenetics of young and aged HSCs as well as of the bone marrow niche wherein HSCs reside. Notably, we summarize the very recent studies which dissect HSC aging at the single-cell level. Furthermore, we review the promising strategies for rejuvenating aged HSC functions. Considering that the incidence of many hematological malignancies is strongly associated with age, our HSC aging review delineates the association between functional changes and molecular mechanisms and may have significant clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Zhang

et al. 2020

J Hematol Oncol

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“…Thus far, many signaling pathways have been implicated in this complex process. However, a more comprehensive understanding remains needed, partly because of the failure to reproduce healthy HSCs for HSC transplantation (HSCT) in vitro 5–8 .…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 signaling regulates hematopoietic stem cell emergence

Tie

Cai

et al. 2019

Exp Mol Med

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Hematopoietic stem cells (HSCs) produce all lineages of mature blood cells for the lifetime of an organism. In vertebrates, HSCs derive from the transition of the hemogenic endothelium (HE) in the floor of the embryonic dorsal aorta. Most recently, a series of proinflammatory factors, such as tumor necrosis factor-α, interferon-γ, and Toll-like receptor 4, have been confirmed to play a key role in HSC specification. However, the full complement of necessary signaling inputs remains unknown to date. Here, we show that interleukin-6R (IL6R) via IL6 is required and sufficient for HSC generation. We found that Notch activates IL6R by regulating its expression in the HE and in HSCs. The secretion of IL6 mainly originates from HSC-independent myeloid cells, but not from HSCs and their adjacent vascular endothelial cells. In addition, blocking IL6 signaling does not affect vascular development or the production of primitive erythrocytes. Taken together, our results uncover a previously obscure relationship between IL6 signaling and HSC production and provide new insights into HSC regeneration using proinflammatory factors in vitro.

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“…The 3D scaffolds might better mimic the physiological environment to promote the differentiation of PSCs (Kraehenbuehl et al, ). Several 3D scaffolds materials have been used for hPSC differentiation (Zhang, Dutton, Su, Zhang, & Ye, ; Lu et al, ), and our lab have been using the self‐assembling peptide hydrogel to generate functional hematopoietic cells from human iPSCs (Xu et al, )…”

Section: Discussionmentioning

confidence: 99%

Generation of hematopoietic cells from mouse pluripotent stem cells in a 3D culture system of self‐assembling peptide hydrogel

Shan

Wang

et al. 2019

Journal Cellular Physiology

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In vitro generation of hematopoietic stem cells from pluripotent stem cells (PSCs) can be regarded as novel therapeutic approaches for replacing bone marrow transplantation without immune rejection or graft versus host disease. To date, many different approaches have been evaluated in terms of directing PSCs toward different hematopoietic cell types, yet, low efficiency and no function restrict the further hematopoietic differentiation study, our research aims to develop a three dimension (3D) hematopoietic differentiation approach that serves as recapitulation of embryonic development in vitro to a degree of complexity not achievable in a two dimension culture system. We first found that mouse PSCs could be efficiently induced to hematopoietic differentiation with an expression of hematopoietic makers, such as c-kit, CD41, and CD45 within self-assembling peptide hydrogel. Colony-forming cells assay results suggested mouse PSCs (mPSCs) could be differentiated into multipotential progenitor cells and 3D induction system derived hematopoietic colonies owned potential of differentiating into lymphocyte cells. In addition, in vivo animal transplantation experiment showed that mPSCs (CD45.2) could be embedded into nonobese diabetic/severe combined immunodeficiency mice (CD45.1) with about 3% engraftment efficiency after 3 weeks transplantation. This study demonstrated that we developed the 3D induction approach that could efficiently promote the hematopoietic differentiation of mPSCs in vitro and obtained the multipotential progenitors that possessed the short-term engraftment potential.

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A synthetic three-dimensional niche system facilitates generation of functional hematopoietic cells from human-induced pluripotent stem cells

Cited by 16 publications

References 63 publications

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Mechanisms and rejuvenation strategies for aged hematopoietic stem cells

Interleukin-6 signaling regulates hematopoietic stem cell emergence

Generation of hematopoietic cells from mouse pluripotent stem cells in a 3D culture system of self‐assembling peptide hydrogel

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