Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-22
·
IF 7.4
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.
研究领域:
眼科学
·
干细胞研究
·
神经科学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Stem Cells International
·
2024
·Vol. 2024
·期 1
·7419270
·
IF 3.8
Rui Zhai,Fumin Tai,Kexin Ding,Xin Tan,Hujie Li,Zhengyue Cao,Changhui Ge,Xiaofei Zheng,Hanjiang Fu
Radiation-induced lung injury (RILI) is frequently observed in patients undergoing radiotherapy for thoracic malignancies, constituting a significant complication that hampers the effectiveness and utilization of tumor treatments. Ionizing radiation exerts both direct and indirect detrimental effects on cellular macromolecules, including DNA, RNA and proteins, but the impact of oxidized RNA in RILI remains inadequately explored. Mesenchymal stem cells (MSCs) can repair injured tissues, and the reparative potential and molecular mechanism of MSCs in treating RILI remains incompletely understood. This study aimed to investigate the therapeutic effects and mechanisms of action of three distinct sources of MSCs, including human umbilical cord mesenchymal stem cells (UCMSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose-derived stem cells (ADSCs), in thoracically irradiated mice. Comparative analysis revealed that all three types of MSCs exhibited the ability to mitigate radiation-induced inflammatory infiltration, alveolar hemorrhage, and alveolar wall thickening in the lung tissue of the mice. MSCs also attenuated RILI by decreasing inflammatory factors, upregulating anti-inflammatory factor expression, and reducing collagen accumulation. Immunohistochemical results showed that all three MSCs reduced radiation-induced cell apoptosis and promoted the regeneration of lung tissue cells. The analysis of malondialdehyde (MDA) and 8-hydroyguanosine (8-OHG) content indicated that MSCs possess reparative properties against radiation-induced oxidative damage in lung tissue. The study provides evidence that UCMSCs are a more appropriate therapeutic option for RILI compared to BMSCs and ADSCs. Additionally, MSCs effectively reduce the accumulation of oxidized RNA in RILI, thereby, presenting a unique avenue for investigating the underlying mechanism of MSC-based treatment for RILI.
研究领域:
肿瘤学
·
干细胞生物学
·
放射生物学
·
肺科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cellular Reprogramming
·
2014
·Vol. 16
·期 5
·379-391
·
IF 2.345
Chao Yang,Liang Sun,Xinghan Li,Li Xie,Mei Yu,Lian Feng,Zongting Jiang,Weihua Guo,Weidong Tian
Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.
研究领域:
干细胞生物学
·
神经科学
·
再生医学
✓ 已验证
DOI
高影响因子
MOLECULES
·
2021
·Vol. 26
·期 3
·604
·
IF 4.412
Dan Xing,Kai Wang,Jun Wu,Yu Zhao,Wei Liu,Jiao Jiao Li,Tingting Gao,Deng Yan,Liu Wang,Jie Hao,Jianhao Lin
Mesenchymalstem cell (MSC)-based therapy is being increasingly explored in preclinical and clinical studies as a regenerative method for treating osteoarthritis (OA). However, the use of primary MSCs is hampered by a number of limitations, including donor heterogeneity and inconsistent cell quality. Here, we tested the therapeutic potential of embryonic stem cell-derived MSCs (ES-MSCs) in anOA rat model. ES-MSCs were generated and identified by morphology, trilineage differentiation and flow cytometry. Sprague Dawley rats were treated with either a single dose (106cells/rat) of ES-MSCs or with three doses spaced one week apart for each dose, starting at four weeks after anterior cruciate ligament transectionto induce OA. Cartilage quality was evaluated at 6 and 10 weeks after treatment with behavioral analysis, macroscopic examination, and histology. At sixweeks after treatment, the groups treated with both single and repeated doses of ES-MSCs had significantly better modified Mankin scores and International Cartilage Repair Society (ICRS) macroscopic scores in the femoral condyle compared to the control group. At 10 weeks after treatment, the repeated doses group had a significantly better ICRS macroscopic scores in the femoral condyle compared to the single dose and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, along with lower Mankin scores in the repeated doses group. In conclusion, treatment with multiple injections of ES-MSCs can ameliorate OA in a rat model. TheES-MSCs have potential to be considered as a regenerative therapy for OA, and can provide an infinite cellular source.Keywords:embryonic stem cells;mesenchymal stem cells;osteoarthritis;cell therapy;tissue repair
研究领域:
再生医学
·
干细胞研究
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2023
·
IF 3.9
Juan Ning,Leisheng Zhang,Hanjing Xie,Lian Chai,Jun Yao
Supernumerary teeth are advantaged sources for high-quality stem cell preparation from both apical papilla (SCAP-Ss) and dental pulp (DPSCs). However, the deficiency of the systematic and detailed comparison of the biological and transcriptomic characteristics of the aforementioned stem cells largely hinders their application in regenerative medicine. Herein, we collected supernumerary teeth for SCAP-S and DPSC isolation and identification by utilizing multiple biological tests (e.g., growth curve, cell cycle and apoptosis, adipogenic and osteogenic differentiation, and quantitative real-time polymerase chain reaction). Furthermore, we took advantage of transcriptome sequencing and multifaceted bioinformatic analyses to dissect the similarities and diversities between them. In this study, we found that SCAP-Ss and DPSCs showed indistinctive signatures in morphology and immunophenotypes, whereas with diversity in cell vitality and multi-lineage differentiation as well as gene expression profiling and differentially expressed genes-associated gene ontology and signaling pathways. Collectively, our data indicated the diversity of the multifaceted signatures of human supernumerary teeth-derived stem cells both at the cellular and molecular levels, which also supplied new references for SCAP-Ss serving as splendid alternative stem cell sources for regenerative medicine purposes.
研究领域:
口腔医学
·
干细胞研究
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
·
2024
·
IF 10.7
Xixi Cai,Hang Zhang,Changqing Mu,Yanjun Chen,Chongzhen He,Mingyu Liu,Thomas Laux,Limin Pi
In multicellular organisms, communication between cells is vital for their fate determination. In plants, the quiescent center (QC) signals to adjacent stem cells to maintain them undifferentiated. However, how surrounding stem cells instruct the QC remains poorly understood. Here, we show that in the Arabidopsis root, microRNA160 (miR160) moves from stele stem cells (SSCs) to the QC, where it degrades the mRNAs of two auxin response factors, ARF10 and ARF17 . This degradation relieves BRAVO from direct transcriptional repression, maintaining QC quiescence. We further identify that blocking miR160 movement due to DNA damage-induced SSC death and restricted symplastic transport reduces BRAVO and WOX5 expression, leading to QC division to replenish damaged stem cells during root regeneration. Together, our results demonstrate that a transcriptional axis initiated by mobile miR160 regulates the QC and stem cell behavior, advancing our understanding of the communication between stem cells and their surrounding cellular environment.
研究领域:
植物生物学
·
分子遗传学
·
发育生物学
✓ 已验证
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2021
·Vol. 12
·期 1
·1-16
·
IF 6.832
Zhou Meiling,Xi Jiaoya,Cheng Yaofeng,Sun Denglong,Shu Peng,Chi Shuiqing,Tian Shuo,Ye Shunan
Background Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for the osteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations. Methods In the present study, the bone marrow samples of patients with ONFH ( n = 16) and patients with the fracture of the femoral neck ( n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFH patients (ONFH-BMSCs) were reprogrammed to iPSCs, following which the iPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups ( n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after the establishment of the ONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of the femoral head necrosis area was analyzed after MSC transplantation. Results The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFH rat model revealed that the iPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in the necrosis region of the femoral head. Conclusion Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in the necrosis area of the femoral head.
研究领域:
干细胞生物学
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cellular Reprogramming
·
2018
·Vol. 20
·期 2
·99-106
·
IF 1.43
Mengya Zhao,Lin Li,Jundong Zhou,Xueyuan Cui,Qingmei Tian,Yaqing Jin,Yimin Zhu
Cancer stem cells (CSCs) are responsible for cancer initiating, recurrence, and drug resistance. Discovery of novel biomarkers for CSCs is helpful for early diagnosis and prognosis. Lung cancer stem cells (LCSCs) were closely related to the occurrence and development of lung cancer. In our study, the important role of miR-2861 in maintaining the stemness of LCSCs was investigated. The LCSC differentiation model was established through introducing serum into the medium of H460 spheres. miR-2861 expression was significantly higher in LCSCs no matter compared to the differentiation cells or normal cells. HDAC5 expression was positively correlated with miR-2861 in LCSCs, and knockdown of miR-2861 decreased the expression of HDAC5, which implied that HDAC5 may be involved in the differentiation of LCSCs mediated by miR-2861. The role of HDAC5 in the regulation of LCSC differentiation was further verified by the inhibitory effect of LMK-235 on the phosphorylation of ERK1/2, which was recognized as the regulator of CSC differentiation. Our study provided a better understanding of miR-2861 and HDAC5 axis in maintaining the stemness of LCSCs and laid a foundation for molecular targeted therapy.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Cell Stem Cell
·
2024
·
IF 19.8
Haiyue Dang,Panpan Feng,Shuning Zhang,Lihua Peng,Shuli Xing,Yuchen Li,Xiang Wen,Liqiang Zhou,Shyamal Goswami,Mingbing Xiao,Nick Barker,Philippe Sansonetti,Parag Kundu
The maternal microbiome influences child health. However, its impact on a given offspring’s stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring’s stem cells, we manipulated maternal microbiota using Akkermansia muciniphila . Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients’ offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings’ stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings’ stem cells and represent a promising target for interventions.
研究领域:
微生物学
·
干细胞生物学
·
发育生物学
·
生理学
·
健康科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYOLETTERS
·
2024
·Vol. 45
·期 2
·114-121
·
IF 1
Song Tao,Liu Baolin
BACKGROUND: Stem cell-laden hydrogel microcapsules construction is important for a wide application in tissue engineering and cell-based medicine, such as building an ideal immune barrier. Challenges are emerging for effectively storing such microcapsules by cryopreservation,
and a large proportion of research has been on the cryopreservation of single cells encapsulated into microcapsules without a core-shell structure. OBJECTIVE: To achieve the effective cryopreservation of stem cell-laden hydrogel microcapsules with a core-shell structure. MATERIALS
AND METHODS: A novel core-shell alginate hydrogel encapsulation method was used to produce mesenchymal stem cell-laden microcapsules by microfluidic technique. RESULTS: This microcapsule could inhibit ice formation to achieve vitreous cryopreservation with a low concentration (2
M) of penetrating cryoprotectants. CONCLUSION: Cell laden hydrogel microcapsules may have the potential to be the basis of a new strategy of cell cryopreservation and applications.
研究领域:
组织工程学
·
细胞生物学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
PLoS Genetics
·
2021
·Vol. 17
·期 7
·e1009649
·
IF 5.917
Kun Wu,Yiming Tang,Qiaoqiao Zhang,Zhangpeng Zhuo,Xiao Sheng,Jingping Huang,Jie’er Ye,Xiaorong Li,Zhiming Liu,Haiyang Chen
The differentiation efficiency of adult stem cells undergoes a significant decline in aged animals, which is closely related to the decline in organ function and age-associated diseases. However, the underlying mechanisms that ultimately lead to this observed decline of the differentiation efficiency of stem cells remain largely unclear. This study investigated Drosophila midguts and identified an obvious upregulation of caudal ( cad ), which encodes a homeobox transcription factor. This factor is traditionally known as a central regulator of embryonic anterior-posterior body axis patterning. This study reports that depletion of cad in intestinal stem/progenitor cells promotes quiescent intestinal stem cells (ISCs) to become activate and produce enterocytes in the midgut under normal gut homeostasis conditions. However, overexpression of cad results in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, this study suggests that cad prevents intestinal stem/progenitor cell differentiation by modulating the Janus kinase/signal transducers and activators of the transcription pathway and Sox21a-GATAe signaling cascade. Importantly, the reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila . This study identified a function of the homeobox gene cad in the modulation of adult stem cell differentiation and suggested a potential gene target for the treatment of age-related diseases induced by age-related stem cell dysfunction.
Adult stem cells undergo an aging-related decline of differentiation efficiency in aged animals. However, the underlying mechanisms that ultimately lead to this observed decline of differentiation efficiency in stem cells still remain largely unclear. By using the Drosophila midgut as a model system, this study identified the homeobox family transcription factor gene caudal ( cad ), the expression of which is significantly upregulated in intestinal stem cells (ISCs) and progenitor cells of aged Drosophila . Depletion of cad promoted quiescent ISCs to become activate and produce enterocytes (ECs) in midguts under normal gut homeostasis conditions; However, overexpression of cad resulted in the failure of ISC differentiation and intestinal epithelial regeneration after injury. Moreover, cad prevents ISC-to-EC differentiation by inhibiting JAK/STAT signaling, and the expressions of Sox21a and GATAe . Reduction of cad expression in intestinal stem/progenitor cells restrained age-associated gut hyperplasia in Drosophila . These findings enable a detailed understanding of the roles of homeobox genes in the modulation of adult stem cell aging in humans. This will be beneficial for the treatment of age-associated diseases that are caused by a functional decline of stem cells.
研究领域:
发育生物学
·
干细胞生物学
·
衰老研究
·
分子遗传学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Tianyuan Zhang,Xixi Zheng,Ruyi Lin,Hao Sun,Honghui Wu,Jinsong Zhang,Shihan Chen,Yaosheng Li,Donghang Xu,Jianqing Gao
The hybridization of liposome with stem cell membranes is an emerging technology to prepare the nanovehicle with the capacity of disease-responsive targeting. However, the long-term storage of this hybrid liposome has received limited attention in the literature, which is essential for its potential applicability in the clinic. Therefore, the preservation of long-term activity of stem cell-hybrid liposome using freeze-drying is investigated in the present study. Mesenchymal stem cell-hybrid liposome is synthesized and its feasibility for freeze-drying under different conditions is examined. Results reveal that pre-freezing the hybrid liposome at −20 °C in Tris buffer solution (pH 7.4) containing 10% trehalose can well preserve the liposomal structure for at least three months. Notably, major membrane proteins on the hybrid liposome are protected in this formulation and CXCR4-associated targeting capacity is maintained both in vitro and in vivo. Consequently, the hybrid liposome stored for three months demonstrates a comparable tumor inhibition as the fresh-prepared one. The present study provides the first insights into the long-term storage of stem cell hybrid liposome using lyophilization, which may make an important step forward in enhancing the long-term stability of these promising biomimetic nanovehicle and ease the logistics and the freeze-storage in the potential clinical applications.
研究领域:
药学
·
生物技术
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）