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公开(公告)号：US20210000880A1
公开(公告)日：2021-01-07
申请号：US16982691
申请日：2019-03-22
发明人： Clive Svendsen , Dhruv Sareen
摘要： Type 2 diabetes (T2D) is a clinical syndrome caused by insufficient insulin secretion for insulin requirements. described herein are compositions and methods for microphysiological MPS models of disease (MODs) for diabetes. These platforms allow one to compare the effect of chronic β-cell stimulation in the presence and absence of patient specific immune cells in IPSC-derived islets from each group. Additionally, one can reproduce the T2D β-cell phenotype, using islets-on-chips will also be exposed to gluco-lipotoxicity. Likewise, skeletal muscle-on-chips are exposed to patient specific activated immune cells, variable motor neuron innervation and lipids characteristic of T2D.
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公开(公告)号：US11913022B2
公开(公告)日：2024-02-27
申请号：US16480778
申请日：2018-01-25
发明人： Ying Qu , Xiaojiang Cui , Dhruv Sareen , Armando E. Giuliano
CPC分类号： C12N5/0631 , A61K35/55 , C12N5/0696 , C12N2506/45 , C12N2533/54 , C12N2533/90
摘要： Human induced pluripotent stem cells (iPSCs) can give rise to multiple cell types and hold great promise in regenerative medicine and disease modeling applications. The Inventors herein developed a reliable two-step protocol to generate human mammary-like organoids from iPSCs. Non-neural ectoderm cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. Gene expression profile analysis suggested that mammary gland function-associated signaling pathways were hallmarks of 10-d differentiated mEBs. The Inventors generated mammary-like organoids from 10-d mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. These organoids expressed common breast tissue, luminal, and basal markers, including estrogen receptor, and could be induced to produce milk protein. These results demonstrate that human iPSCs can be directed in vitro toward mammary lineage differentiation.
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公开(公告)号：US20230174946A1
公开(公告)日：2023-06-08
申请号：US17922162
申请日：2021-04-30
发明人： Barry R. Stripp , Apoorva Mulay , Bindu Konda , Arun Sharma , Clive Svendsen , Vaithilingaraja Arumugaswami , Dhruv Sareen , Hanan Shaharuddin , Victoria Wang , Roberta S. Santos
CPC分类号： C12N5/0676 , C12M23/16 , C12N5/0657 , C12N5/0688 , C12N2503/02 , C12N2506/45
摘要： Described herein are particular infection model systems, methods of studying infection, and method of screening compounds in various model systems. Particularly, SARS-CoV-2 is studied in these organ and infection models.
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公开(公告)号：US20200370023A1
公开(公告)日：2020-11-26
申请号：US16919456
申请日：2020-07-02
发明人： Dhruv Sareen , Loren A. Ornelas , Clive Svendsen
IPC分类号： C12N5/074
摘要： Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.
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25.发明申请公开(公告)号：US20200332316A1
公开(公告)日：2020-10-22
申请号：US16917008
申请日：2020-06-30
发明人： Xiaojiang Cui , Dhruv Sareen , Loren A. Ornelas
摘要： Described herein are reprogramming techniques allowing for production of mammary-derived iPSCs (“m-iPSCs”). The m-iPSCs described herein exhibit all the hallmarks of stem cell identity including round cluster, bright colony morphology, clonal expansion, and pluripotent marker expression (alkaline phosphatase expression, Oct-4, nanog, etc.) Further refined techniques allow for generation of m-iPSCs under essentially defined conditions.
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公开(公告)号：US20200157508A1
公开(公告)日：2020-05-21
申请号：US16614924
申请日：2018-05-18
摘要： Induced pluripotent stem cell (iPSC)-based organoid technology has tremendous potential to elucidate the intestinal and colonic epithelium's role in health and disease. Described herein are methods and compositions for generation of intestinal and colonic cells from iPSCs. Derivation of iPSCs from subjected afflicted with early onset and very early onset Inflammatory Bowel Disease (IBD), serves as an excellent model for understanding disease pathogenesis.
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公开(公告)号：US20190153395A1
公开(公告)日：2019-05-23
申请号：US16074747
申请日：2017-02-01
发明人： Robert Barrett , Clive Svendsen , Stephan R. Targan , Michael Workman , Dhruv Sareen , Uthra Rajamani
摘要： Organs-on-chips are microfluidic devices for culturing living cells in micrometer sized chambers in order to model physiological functions of tissues and organs. Engineered patterning and continuous fluid flow in these devices has allowed culturing of intestinal cells bearing physiologically relevant features and sustained exposure to bacteria while maintaining cellular viability, thereby allowing study of inflammatory bowl diseases. However, existing intestinal cells do not possess all physiologically relevant subtypes, do not possess the repertoire of genetic variations, or allow for study of other important cellular actors such as immune cells. Use of iPSC-derived epithelium, including IBD patient-specific cells, allows for superior disease modeling by capturing the multi-faceted nature of the disease.
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28.发明公开公开(公告)号：US20240158757A1
公开(公告)日：2024-05-16
申请号：US18352622
申请日：2023-07-14
发明人： Dhruv Sareen , Loren Ornelas , Robert Barrett
CPC分类号： C12N5/0696 , A61K35/17 , C12N15/00 , C12N15/86 , A61K2035/124 , C12N2501/115 , C12N2501/15 , C12N2501/16 , C12N2501/235 , C12N2501/48 , C12N2501/602 , C12N2501/603 , C12N2501/604 , C12N2501/606 , C12N2501/608 , C12N2501/727 , C12N2501/999 , C12N2506/11
摘要： Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors, including generation of iPSCs from lymphoblastoid B-cells and lymphoblastoid B-cell lines. Such methods and compositions find use in regenerative medicine applications.
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公开(公告)号：US20230340420A1
公开(公告)日：2023-10-26
申请号：US18151625
申请日：2023-01-09
发明人： Dhruv Sareen , Loren A. Ornelas , Clive Svendsen
CPC分类号： C12N5/0696 , C12N5/0018 , C12N2500/12 , C12N2500/38 , C12N2501/115 , C12N2501/2302 , C12N2501/2303 , C12N2501/2306 , C12N2501/33 , C12N2501/60 , C12N2501/602 , C12N2501/603 , C12N2501/604 , C12N2501/606 , C12N2501/998 , C12N2506/11 , C12N2506/115 , C12N2510/00 , C12N2533/52
摘要： Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.
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公开(公告)号：US20210269776A1
公开(公告)日：2021-09-02
申请号：US17254783
申请日：2019-06-26
发明人： Andrew R. Gross , Dhruv Sareen
摘要： Bioprinting is the layer-by-layer construction of synthetic tissues or scaffolds. Described herein is a motorized extruder which can precisely extrude and retract extrudate such as bioinks in a compact and rapidly-loadable form-factor. This includes a compact bioprinter using a stepper motor coupled with a threaded shaft to directly move the plunger of an extruder. This pneumatic-mechanical system obviates the needs for pneumatic tubing, rods, or other complex elements of existing designs. The direct drive design further allows for a lighter, smaller gantry that is capable of more precise fabrication of bioprinted constructions. This includes delicate vasculature systems that are beyond limits of existing bioprinting technologies.
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