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hiPSCs
ACS Applied Materials & Interfaces · 2025 · IF 8.2

Efficient Differentiation of hiPSCs into hMSC-like Cells under Chemically Defined Conditions on Temperature-Sensitive Micropatterned Surfaces

Pengxia Zhang,Maoying Liu,Suying Pei,Hongxin Huang,Zhengyan Zhao,Ling Yang,Wen Pan,Siyi Li,Qifeng Bai,Rui Zhang,Ping Zhou

The fairness of long-term self-renewal and robust cell proliferation limits the applications of human mesenchymal stem cells (hMSCs) in regenerative medicine. Inducing hMSCs from human-induced pluripotent stem cells (hiPSCs), which have the advantages of autogenous and no cell number issues, is highly valuable. However, current induction methods using FBS-containing mesenchymal culture medium have problems, including immunogenicity, microbial contamination, and low efficiency. To solve these problems, we propose a chemically defined induction protocol incorporating transforming growth factor-beta 1 and retinoic acid (RA) additives in serum-free E6 medium for the suspension induction of embryoid bodies in hiPSCs. Additionally, microgroove-patterned polydimethylsiloxane surfaces coated with temperature-sensitive N-isopropylacrylamide (PNIPAAm) were prepared for efficient harvesting and purification of induced hiPSC-derived hMSCs (hiPSC-MSCs). The results showed that both supplementation with RA and patterned microgrooves with a width of 20 μm could accelerate the induction of hiPSC-MSCs, realizing the promising scalable production of homogeneous cells. This study successfully established a chemically defined induction protocol and utilized patterned surfaces to obtain clinically applicable hiPSC-MSCs, which show great promise in tissue engineering, gene therapy, and cell transplantation.

CAS / MDL: 60-00-4 2210-25-5
研究领域: 再生医学 · 干细胞研究 · 组织工程
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Biomaterials Science · 2020 ·Vol. 8 ·期 19 ·5476-5488 · IF 6.183

One-step synthesis of composite hydrogel capsules to support liver organoid generation from hiPSCs

Yaqing Wang,Haitao Liu,Min Zhang,Hui Wang,Wenwen Chen,Jianhua Qin

Advances in biomaterials, especially in hydrogels, have offered great opportunities for stem cell organoid engineering with higher controllability and fidelity. Here, we propose a novel strategy for one-step synthesis of composite hydrogel capsules (CHCs) that enable engineering liver organoids from human induced pluripotent stem cells (hiPSCs) in an oil-free droplet microfluidic system. The CHCs composed of a fibrin hydrogel core and an alginate–chitosan composite shell are synthesized by an enzymatic crosslinking reaction and electrostatic complexation within stable aqueous emulsions. The proposed CHCs exhibit high uniformity with biocompatibility, stability and high-throughput properties, as well as defined compositions. Moreover, the established system enables 3D culture, differentiation and self-organized formation of liver organoids in a continuous process by encapsulating hepatocyte-like cells derived from hiPSCs. The encapsulated liver organoids consisting of hepatocyte- and cholangiocyte-like cells show favorable cell viability and growth with consistent size. Furthermore, they maintain proper liver-specific functions including urea synthesis and albumin secretion, replicating the key features of the human liver. By combining stem cell biology, defined hydrogels and the droplet microfluidic technique, the proposed system is easy-to-operate, scalable and stable to engineer stem cell organoids, which may offer a robust platform to advance organoid research and translational applications.

研究领域: 生物材料 · 干细胞生物学 · 组织工程 · 微流控技术 · 类器官研究
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CARBOHYDRATE POLYMERS · 2025 · IF 12.5

Acetylated glucomannan-CNT scaffolds with dual-drug release promote hiPSCs-driven cortical regeneration by suppressing inflammation and anoikis

Yue Gao,Wenxi Li,Wanting Lu,Fuqiang Tang,Xian Xiao,Yinggang Li,Jiaxing Huang,Zhiqi Liang,Yuqing Wu,Yanwen Li,Qingjian Zou,Liangxue Lai,Yanxian Feng,Song Ang,Min Chen

The regenerative capacity of the central nervous system is extremely limited, posing significant challenges for repairing brain injuries. Human induced pluripotent stem cells (hiPSCs) offer a promising cell source for neural regeneration, but their clinical application is hindered by inefficient neuronal differentiation, and poor post-transplant survival. To overcome these challenges, we prepared electrospun fibrous membranes composed of acetylated glucomannan, gelatin, polycaprolactone, and carbon nanotubes. These scaffolds exhibited anti-inflammatory properties in vitro and in vivo . Their excellent adhesion and support properties mimic the extracellular matrix, facilitating the 3D culture of our previous engineered NILB-hiPSCs in vitro . After loading with doxycycline (differentiation inducer) and cyclosporin A (immunosuppressant), the scaffolds achieved sustained release of these agents, ensuring timely neuronal differentiation and maintaining localized immunosuppression, thereby circumventing the need for high systemic doses. Moreover, the composites improved the survival and differentiation of NILB-hiPSCs, promoting the neural repairment in controlled cortex injury mice. Our study highlights the importance of customized multifunctional biomaterials in stem cell transplantation therapy.

CAS / MDL: 9000-70-8
研究领域: 生物材料 · 干细胞治疗 · 神经组织工程 · 药物递送系统 · 再生医学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Engineering microcapsules to construct vascularized human brain organoids

Yujuan Zhu,Lingyu Sun,Xiao Fu,Junying Liu,Zhenjiang Liang,Hui Tan,Weiping Li,Yuanjin Zhao

Brain organoid is a promising technique with potential applications in developmental study, drug discovery and regenerative medicine, however, its practical values are restricted by poor flexibility, and lack of near-physiological structures or functions. Here, we present a multidisciplinary strategy to engineer novel vascularized human induced pluripotent stem cells (hiPSCs)-derived brain organoids system with biomimetic features using microfluidic hydrogel microcapsules. Due to the precise fluids control of microfluidic electrospray technology , its generated microcapsules enable the efficient encapsulation of hiPSCs-derived neural cells and formation of uniform human brain organoids. Through embedding microcapsules in hydrogel, vascularized brain organoids with structured organization and reasonable tissue size are established. We have found hiPSC-derived brain organoids with in vivo-like neural identity, brain region and layered cortex, as well as complex vascular networks, proving the capability to generate more relevant model of vascularized human brain. Thus, this biomimetic neural system could be injected for traumatic brain injury, and in vivo animal study has shown graft-to-host functional neural connectivity and neural regeneration, suggesting the organ-level functions for tissue repair. Our studies indicated that this simple, scalable and flexible system could be applied to develop biomimetic human tissues, which potentially advanced the organoid models for biomedical applications.

研究领域: 生物医学工程 · 神经科学 · 再生医学 · 干细胞研究
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JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION · 2023 ·Vol. 37 ·期 6 ·1271-1278 · IF 1.6

Integrated Organ-on-a-chip with Human-induced Pluripotent Stem Cells Directional Differentiation for 3D Skin Model Generation

Luo Zhang,Gong Chaihong,Mao Xiaowei,Wang Zhe,Liu Zhifan,Ben Yali,Zhang Weiying

Keratinocytes and fibroblasts, derived from hiPSCs, were used to construct the human epidermal model by a culture patch made by monolayer poly-(lactic-co-glycolic acid) (PLGA) nanofibers and a human skin-on-a-chip device. Unlike the conventional culture dish method, two different epidermal cells are successfully adhered to the front and back sides of the patch, which produces a three-dimensional nanofibrous scaffold similar to a natural extracellular matrix before the patch was cultured in the skin-on-a-chip device to mimic the physiological conditions of human skin. As expected, the differentiated hiPSCs show the expression of keratinocyte- and fibroblast- specific proteins on the patch, and the layering is found between these two kinds of cells, indicating that this approach creates a powerful in vitro system for modeling skin development and diseases.

CAS / MDL: 24650-42-8
研究领域: 组织工程 · 再生医学 · 干细胞研究 · 生物医学工程
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ACS Biomaterials Science & Engineering · 2024 · IF 5.4

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization

Weidong Wu,Youjun Liu,Renfeng Liu,Yuhao Wang,Yuqi Zhao,Hui Li,Botao Lu,Cheng Ju,Xinlin Gao,Hailiang Xu,Yulin Cao,Shixiang Cheng,Zhiyuan Wang,Shuaijun Jia,Chunping Hu,Lei Zhu,Dingjun Hao

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

研究领域: 神经科学 · 干细胞生物学 · 组织工程 · 再生医学 · 疾病建模
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