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Polymer Chemistry · 2019 ·Vol. 10 ·期 18 ·2305-2315 · IF 4.76

Thermoresponsive dendronized chitosan-based hydrogels as injectable stem cell carriers

Xiacong Zhang,Lin Cheng,Letian Feng,Yu Peng,Zhimin Zhou,Guoyong Yin,Wen Li,Afang Zhang

Stimulus-responsive injectable hydrogels with self-healing properties are promising materials for the delivery of bioactives owing to their protection of the payloads, minimally invasive procedures and site-specific administration. In this work, we report on a type of thermoresponsive dendronized chitosan-based (G1-CS) injectable hydrogel and its potential as scaffolds for stem cell delivery. G1-CS was synthesized through dendronization of chitosan with dendritic oligoethylene glycols (OEGs) to afford characteristic thermoresponsiveness, and its further crosslinking through dynamic covalent Schiff-base chemistry generated the hydrogels. The mechanical properties of the obtained hydrogels are weak with a storage modulus around 0.2 kPa at room temperature, which can be significantly improved to about 1.4 kPa at 37 °C. This feature comes remarkably from thermally induced aggregation and a simultaneously enhanced Schiff-base reaction in an aqueous phase, resulting in promoted crosslinking of the hydrogel network and immediate gelation under physiological conditions. The Schiff-base linkage also endows the hydrogels with shear-thinning and self-healing properties, which facilitate the injection process of the hydrogels and maintenance of their stability. G1-CS hydrogels were examined to encapsulate stem cells. After long term (14 days) culture, the cells exhibited high viability and well maintained their differentiation potential. We therefore believe that hydrogels from this dendronized chitosan, featuring biocompatibility, thermoresponsiveness, self-healing ability, and enhanced mechanical properties, can serve as promising scaffolds for drug delivery and tissue engineering.

CAS / MDL: 9012-76-4
研究领域: 材料科学 · 生物材料 · 组织工程 · 干细胞研究
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ACS Applied Materials & Interfaces · 2015 · IF 6.723

Photo-Activatable Substrates for Site-Specific Differentiation of Stem Cells

Kai Han,Wei-Na Yin,Jin-Xuan Fan,Feng-Yi Cao,Xian-Zheng Zhang

In this report, a UV sensitive, PEGylated PFSSTKTC (Pro-Phe-Ser-Ser-Thr-Lys-Thr-Cys) peptide was modified on quartz substrate to investigate the spatial controlled differentiation of stem cells. This substrate could restrict the cell adhesion due to the steric hindrance of PEG shell. With UV irradiation, PFSSTKTC became exposed owing to the breakage of o-nitrobenzyl group with the detachment of PEG shell. The irradiation boundary on substrate was stable in the long term. The in vitro osteogenic differentiation results revealed that under the site-specific irradiation, the mesenchymal stem cells (MSCs) could specifically differentiate into osteoblast under the induction of PFSSTKTC peptide. This photoactivatable biomaterial shows great potential for region controllable and precise MSCs differentiation.

研究领域: 生物材料 · 干细胞生物学 · 组织工程
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

Kartogenin-Incorporated Thermogel Supports Stem Cells for Significant Cartilage Regeneration

Xuezhou Li,Jianxun Ding,Zhengzheng Zhang,Modi Yang,Jiakuo Yu,Jincheng Wang,Fei Chang,Xuesi Chen

Recently, cartilage tissue engineering (CTE) attracts increasing attention in cartilage defect repair. In this work, kartogenin (KGN), an emerging chondroinductive nonprotein small molecule, was incorporated into a thermogel of poly(l-lactide-co-glycolide)–poly(ethylene glycol)–poly(l-lactide-co-glycolide) (PLGA–PEG–PLGA) to fabricate an appropriate microenvironment of bone marrow mesenchymal stem cells (BMSCs) for effective cartilage regeneration. More integrative and smoother repaired articular surface, more abundant characteristic glycosaminoglycans (GAGs) and collagen II (COL II), and less degeneration of normal cartilage were obtained in the KGN and BMSCs coloaded thermogel group in vivo. In conclusion, the KGN-loaded PLGA–PEG–PLGA thermogel can be utilized as an alternative support for BMSCs to regenerate damaged cartilage in vivo.

CAS / MDL: 9004-07-3 9004-06-2
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Frontiers in Cell and Developmental Biology · 2021 · IF 6.684

Microtubule Stabilization Enhances the Chondrogenesis of Synovial Mesenchymal Stem Cells

Li Jiawei,Sun Ziying,Lv Zhongyang,Jiang Huiming,Liu Anlong,Wang Maochun,Tan Guihua,Guo Hu,Sun Heng,Wu Rui,Xu Xingquan,Yan Wenjin,Jiang Qing,Ikegawa Shiro,Shi Dongquan

Mesenchymal stem cells (MSCs) are well known for their multi-directional differentiation potential and are widely applied in cartilage and bone disease. Synovial mesenchymal stem cells (SMSCs) exhibit a high proliferation rate, low immunogenicity, and greater chondrogenic differentiation potential. Microtubule (MT) plays a key role in various cellular processes. Perturbation of MT stability and their associated proteins is an underlying cause for diseases. Little is known about the role of MT stabilization in the differentiation and homeostasis of SMSCs. In this study, we demonstrated that MT stabilization via docetaxel treatment had a significant effect on enhancing the chondrogenic differentiation of SMSCs. MT stabilization inhibited the expression of Yes-associated proteins (YAP) and the formation of primary cilia in SMSCs to drive chondrogenesis. This finding suggested that MT stabilization might be a promising therapeutic target of cartilage regeneration.

研究领域: 干细胞生物学 · 骨科 · 再生医学
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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA · 2021 ·Vol. 118 ·期 43 ·e2112704118 · IF 11.205

Roe-inspired stem cell microcapsules for inflammatory bowel disease treatment

Guopu Chen,Fengyuan Wang,Min Nie,Hui Zhang,Han Zhang,Yuanjin Zhao

Mesenchymal stem cells (MSCs), which exert regulatory effects on various immune cells, have been a promising therapy for inflammatory bowel disease treatment. However, their therapeutic effects are limited by lack of nutritional supply, immune system attack, and low accumulation on the target site. Here, inspired by the natural incubation mechanism of roe, we present immune-isolating, wet-adhesive, and nutrient-rich microcapsules for therapeutic MSCs encapsulation. The adhesive shells were fabricated by ionic cross-linking of alginate and visible curing of epsilon-poly-L-lysine-graft-methacrylamide and dopamine methacrylamide, which encapsulated the liquid core of the MSCs and roe proteins. Due to the core-shell construction of the resultant microcapsules, the MSCs might escape from attack of the immune system while still maintaining immunomodulating functions. In addition, the roe proteins encapsulated in the core phase offered sufficient nutrient supply for MSCs’ survival and proliferation. Furthermore, after intraperitoneal transplantation, the wet-adhesive radicals on the shell surface could immobilize the MSCs-encapsulating microcapsules onto the bowel. Based on these features, practical values of the roe-inspired microcapsules with MSCs encapsulation were demonstrated by applying them to treat dextran sulfate sodium (DSS)–induced colitis through increasing residence time, regulating immune imbalance, and relieving disease progression. We believe that the proposed roe-inspired microcapsules with MSCs encapsulation are potential for clinical application.

研究领域: 医学 · 生物材料学 · 免疫学
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Advanced Science · 2026 · IF 14.1

TTNPB Promotes Human Pluripotent Stem Cell-to-Neural Stem Cell Transition via Modulation of Chromatin Accessibility and the S-(5′-adenosyl)-L-homocysteine/Choline Metabolic Network

Ruilin Du,Yudi Ren,Qiaoqiao Meng,Peng Wei,Ruyu Zhu,Junjie Bao,Ye Yang,Shuo Yan,Chaorong Yue,Xueying Zhu,Shuo Cao,Chunxia Hao,Wei Sun,Yongli Song,Xihe Li,Zhimin Wu,Siqin Bao,Yanglin Chen

Efficient derivation of neural stem cells (NSCs) from human pluripotent stem cells (PSCs) is crucial in regenerative medicine. Here, we report that the combined application of the retinoic acid receptor agonist TTNPB and the GSK3β inhibitor CHIR99021 in a chemically defined medium enabled the induction of a highly advanced NSCs (ANSCs) population from PSCs. ANSCs display robust neuroectodermal gene expression and a heightened capacity for neural lineage commitment. The combination of TTNPB and CHIR99021 markedly enhanced global chromatin accessibility, particularly at neuroectoderm-specific regulatory elements such as PAX6 and SOX1 , in parallel with reduced accessibility at the loci of pluripotency factors. Notably, TTNPB alone also exerts a marked effect in enhancing chromatin accessibility. Untargeted metabolomic analysis identified a distinct neural-ectoderm associated metabolic state in ANSCs, prominently characterized by elevated choline, alongside S-(5′-adenosyl)-L-homocysteine, adenosine 5′-diphosphate, and glutathione. Exogenous addition of these metabolites was sufficient to induce neuroectodermal marker expression, highlighting the instructive role of the metabolic network in neural fate induction. Moreover, functional studies showed that ANSCs enabled engraftment into depressed rat hippocampi and restored depression-like behavioral deficits. Our study presents a novel small-molecule strategy that leverages TTNPB-centered epigenetic remodeling and metabolic reprogramming as dual mechanisms driving neural differentiation.

CAS / MDL: 58-64-0 67-48-1 70-18-8
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ACS Biomaterials Science & Engineering · 2023 · IF 5.8

Potential of an Aligned Porous Hydrogel Scaffold Combined with Periodontal Ligament Stem Cells or Gingival Mesenchymal Stem Cells to Promote Tissue Regeneration in Rat Periodontal Defects

Wenhao Wang,Ao Wang,Gaofu Hu,Mengyao Bian,Lili Chen,Qian Zhao,Weilian Sun,Yanmin Wu

Periodontal tissue regeneration is a major challenge in tissue engineering due to its regenerated environment complexity. It aims to regenerate not only the supporting alveolar bone and cementum around teeth but also the key connecting periodontal ligament. Herein, a constructed aligned porous hydrogel scaffold carrying cells based on chitosan (CHI) and oxidized chondroitin sulfate (OCS) treated with a freeze-casting technique was fabricated, which aimed to induce the arrangement of periodontal tissue regeneration. The microscopic morphology and physical and chemical properties of the hydrogel scaffold were evaluated. The biocompatibilities with periodontal ligament stem cells (PDLSCs) or gingival-derived mesenchymal stem cells (GMSCs) were verified, respectively, by Live/Dead staining and CCK8 in vitro. Furthermore, the regeneration effect of the aligned porous hydrogel scaffold combined with PDLSCs and GMSCs was evaluated in vivo. The biocompatibility experiments showed no statistical significance between the hydrogel culture group and blank control (P > 0.05). In a rat periodontal defect model, PDLSC and GMSC hydrogel experimental groups showed more pronounced bone tissue repair than the blank control (P < 0.05) in micro-CT. In addition, there was more tissue repair (P < 0.05) of PDLSC and GMSC hydrogel groups from histological staining images. Higher expressions of OPN, Runx-2, and COL-I were detected in both of the above groups via immunohistochemistry staining. More importantly, the group with the aligned porous hydrogel induced more order periodontal ligament formation than that with the ordinary hydrogel in Masson’s trichrome analysis. Collectively, it is expected to promote periodontal tissue regeneration utilizing an aligned porous hydrogel scaffold combined with PDLSCs and GMSCs (CHI–OCS–PDLSC/GMSC composite), which provides an alternative possibility for clinical application.

CAS / MDL: 9007-28-7 39455-18-0
研究领域: 组织工程 · 牙科材料 · 干细胞生物学 · 再生医学 · 生物医学工程
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Journal of Translational Medicine · 2023 ·Vol. 21 ·期 1 ·1-22 · IF 7.4

Comparison of retinal degeneration treatment with four types of different mesenchymal stem cells, human induced pluripotent stem cells and RPE cells in a rat retinal degeneration model

Liu Qian,Liu Jun,Guo Minmei,Sung Tzu-Cheng,Wang Ting,Yu Tao,Tian Zeyu,Fan Guoping,Wu Wencan,Higuchi Akon

Background Retinal degeneration (RD) is a group of disorders on irreversible vision loss. Multiple types of stem cells were used in clinical trials for RD treatment. However, it remains unknown what kinds of stem cells are most effective for the treatment. Therefore, we investigated the subretinal transplantation of several types of stem cells, human adipose-derived stem cells (hADSCs), amniotic fluid stem cells (hAFSCs), bone marrow stem cells (hBMSCs), dental pulp stem cells (hDPSCs), induced pluripotent stem cell (hiPSC), and hiPSC-derived retinal pigment epithelium (RPE) cells for protection effects, paracrine effects and treatment efficiency in an RD disease model rats.Methods The generation and characterization of these stem cells and hiPSC-derived RPE cells were performed before transplantation. The stem cells or hiPSC-derived RPE cell suspension labelled with CellTracker Green to detect transplanted cells were delivered into the subretinal space of 3-week-old RCS rats. The control group received subretinal PBS injection or non-injection. A series of detections including fundus photography, optomotor response (OMR) evaluations, light–dark box testing, electroretinography (ERG), and hematoxylin and eosin (HE) staining of retinal sections were conducted after subretinal injection of the cells.Results Each stem cell, hiPSC-derived RPE cell or PBS (blank experiment) was successfully transplanted into at least six RCS rats subretinally. Compared with the control rats, RCS rats subjected to subretinal transplantation of any stem cells except hiPSCs showed higher ERG waves (p < 0.05) and quantitative OMR (qOMR) index values (hADSCs: 1.166, hAFSCs: 1.249, hBMSCs: 1.098, hDPSCs: 1.238, hiPSCs: 1.208, hiPSC-RPE cells: 1.294, non-injection: 1.03, PBS: 1.06), which indicated better visual function, at 4 weeks post-injection. However, only rats that received hiPSC-derived RPE cells maintained their visual function at 8 weeks post-injection (p < 0.05). The outer nuclear layer thickness observed in histological sections after HE staining showed the same pattern as the ERG and qOMR results.Conclusion sCompared to hiPSC-derived RPE cells, adult and fetal stem cells yielded improvements in visual function for up to 4 weeks post-injection; this outcome was mainly based on the paracrine effects of several types of growth factors secreted by the stem cells. Patients with RD will benefit from the stem cell therapy.

CAS / MDL: 59865-13-3
研究领域: 眼科学 · 干细胞研究 · 神经科学 · 再生医学
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Nano Energy · 2018 · IF 13.12

Cation and anion Co-doping synergy to improve structural stability of Li- and Mn-rich layered cathode materials for lithium-ion batteries

Guorong Chen,Juan An,Yiming Meng,Changzhou Yuan,Bryan Matthews,Fei Dou,Liyi Shi,Yongfeng Zhou,Pingan Song,Gang Wu,Dengsong Zhang

Cobalt-free Li and Mn-rich layered cathode materials are promising for next generation lithium ion batteries due to their high specific capacity and low cost. However, these materials are facing serious issues, such as structural collapse due to volume shrinkage during Ni 2+ oxidation to Ni 4+ and oxygen vacancy generation over 4.5V. In this work, we report a strategy to address the issue of volume shrinkage caused by structural deformation via constructing a large-size rigid frame by simultaneously doping inactive and large radius atoms of Cd and S. This strategy significantly reduces the volume shrinkage when fully delithiated relative to the pristine material. The Cd- and S-doped cathode materials present a highly reversible structure, which were determined by using HAADF-STEM and in-situ XRD characterization. The doped Cd and S atoms act as supporting atoms and synergistically enlarge the layer spacing of crystalline from 0.455 to 0.483 nm. The in-situ XRD monitors the structural changes in real time during charging and discharging processes, further verifying structural stability during cycling. Due to the unique structural properites, an initial capacity of 268.5 mAh g −1 at 0.1 C along with a good rate capacity of 153.8 mAh g −1 at 5 C were achieved. Also, a capacity of 243.4 mAh g-1 at 0.1 C over 80 cycles indicate good cyclic stability of the co-doped Li- and Mn-rich layered cathode.

研究领域: 材料科学 · 电化学 · 电池技术
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Theranostics · 2024 · IF 12.4

Nicotinamide mononucleotide enhances fracture healing by promoting skeletal stem cell proliferation

Yitian Shi,Jiayin Peng,Mengfan Liu,Xiling Qi,Siyu Li,Qiangqiang Li,Qing Jiang,Liming Zheng,Jiankun Xu,Yun Zhao,Yifeng Zhang

The process of skeletal regeneration initiated by stem cells following injury, especially in fractures, is significantly impaired by aging and adverse factors. Nicotinamide mononucleotide (NMN), a critical endogenous precursor of nicotinamide adenine dinucleotide (NAD), has garnered extensive attention for its multifaceted regulatory functions in living organisms and its wide-ranging therapeutic potential. However, whether NMN contributes to trauma-induced skeletal regeneration remains unclear. Methods : The transverse femoral shaft fracture model was employed to evaluate the potential advantages of NMN administration for overall repair during the initial fracture stages in male mice through micro-CT analysis, histochemistry, and biomechanical testing. The pro-proliferative function of NMN on skeletal stem cells (SSCs) was investigated through flow cytometry, qRT-PCR, NAD content measurement, and cell proliferation assay. Results : In this study, we observed that the administration of NMN during the initial phase of fracture in mice led to a larger callus and corresponding improvement in micro-CT parameters. NMN enhances the cartilaginous component of the callus by elevating the NAD content, consequently accelerating subsequent endochondral ossification and the fracture healing process. Subsequent analyses elucidated that NMN was beneficial in promoting the expansion of diverse stem cells in vivo and in vitro potentially via modulation of the Notch signaling pathway. Moreover, the depletion of macrophages profoundly obstructs the proliferation of SSCs. Conclusion : Our discoveries provide a potential strategy for enhancing fracture healing through stimulation of callus SSC proliferation at an early stage, shedding light on the translational value of NMN as an enhancer for skeletal regeneration and highlighting the pivotal role of macrophage-stem cell interactions in governing the regenerative influence of NMN on stem cells.

研究领域: 再生医学 · 干细胞生物学 · 骨科 · 分子生物学
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Nature Chemical Biology · 2024 · IF 12.9

Control of DNA demethylation by superoxide anion in plant stem cells

Wang Shiwen,Liu Min,Hu Dongping,Dong Zhicheng,Zhao Zhong

Superoxide anion is thought to be a natural by-product with strong oxidizing ability in all living organisms and was recently found to accumulate in plant meristems to maintain stem cells in the shoot and undifferentiated meristematic cells in the root. Here we show that the DNA demethylase repressor of silencing 1 (ROS1) is one of the direct targets of superoxide in stem cells. The Fe–S clusters in ROS1 are oxidized by superoxide to activate its DNA glycosylase/lyase activity. We demonstrate that superoxide extensively participates in the establishment of active DNA demethylation in the Arabidopsis genome and that ARABIDOPSIS RESPONSE REGULATOR 12 acts downstream of ROS1-mediated superoxide signaling to maintain stem cell fate. Our results provide a mechanistic framework for superoxide control of the stem cell niche and demonstrate how redox and DNA demethylation interact to define stem cell fate in plants.

研究领域: 植物生物学 · 表观遗传学 · 干细胞生物学
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RUSSIAN JOURNAL OF PLANT PHYSIOLOGY · 2018 ·Vol. 65 ·期 3 ·372-383 · IF 0.816

Physiological and Molecular Changes during Lily Underground Stem Axillary Bulbils Formation

Zhang Y.,Yong Y. B.,Wang Q.,Lu Y. M.

Lily is regarded as one kind of the most economically important cut flowers in China. In this paper, lily cultivar ‘Aladdin’ ( Lilium longiflorum × Lilium asiatic ) was chosen as experimental material for its distinct high propagation coefficient in nature and three main conclusions were achieved. Firstly, our observation results revealed that the noticeable propagation coefficient of ‘Aladdin’ depended on strong capacity to form many underground stem axillary bulbils positioned on underground node of plant after 70 days of cultivation and having 1 cm flower buds. Secondly, in terms of physiological changes, zeatin riboside (ZR) relative concentration, soluble sugar and starch content peak when and where such bulbils are forming. Finally, two KNOX family Lilium genes were sequenced completely and one BELL family gene was sequenced partly; besides, there might be an interaction between KNOX-2 and BELL protein to accomplish their functions in bulbils organogenesis according to qRT-PCR results. As far as we know, it is the first time to study the formation mechanism of lily underground stem axillary bulbils. We illustrated physiological and molecular profiles, as well as offered a new prospect to lily molecular breeding in the future.

研究领域: 植物学 · 分子生物学 · 植物生理学 · 遗传学
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