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公开(公告)号：US20240254449A1
公开(公告)日：2024-08-01
申请号：US18626855
申请日：2024-04-04
发明人： S. Jordan Kerns , Norman Wen , Carol Lucchesi , Christopher David Hinojosa , Jacob Fraser , Jefferson Puerta , Geraldine Hamilton , Robert Barrett , Clive Svendsen , Daniel Levner , Stephen R. Targan , Michael Workman , Dhruv Sareen , Uthra Rajamani , Magdalena Kasendra
CPC分类号： C12N5/0679 , C12M21/08 , C12M23/16 , C12N5/0618 , C12N5/0696 , G01N33/5005 , C12N2501/11 , C12N2501/119 , C12N2501/13 , C12N2501/155 , C12N2501/16 , C12N2501/24 , C12N2501/25 , C12N2501/415 , C12N2501/998 , C12N2501/999 , C12N2506/45 , C12N2535/00
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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12.发明公开公开(公告)号：US20240093154A1
公开(公告)日：2024-03-21
申请号：US18272969
申请日：2022-01-31
CPC分类号： C12N5/0676 , A61K35/39 , A61P3/10 , C12N5/0018
摘要： Diabetes is a clinical condition that affects millions of people worldwide, and is treated by insulin replacement therapies. New strategies to create scalable and compatible pancreatic islets containing insulin-producing beta cells are necessary as an alternative to limited supply of cadaveric islets or multiple exogenous insulin applications. Improvements are still necessary since many immature polyhormonal cells remain, and cannot attain a monohormonal state. During human development, pancreas co-develops with endothelium and shares signals, allowing for better maturation of beta cells, and this is not included in the current differentiation protocols. The organchip microfluidic devices allows dynamic co-culture of different cells, thus resembling in vivo physiology. Here the Inventors establish organ-chip models co-culturing human iPSC-derived pancreatic precursors with iPSC-derived endothelial cells to obtain more functional and monohormonal iPSC-derived beta cells.
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公开(公告)号：US11767513B2
公开(公告)日：2023-09-26
申请号：US16492906
申请日：2018-03-14
发明人： Dhruv Sareen , Berhan Mandefro , Anjoscha Kaus
CPC分类号： C12N5/0658 , C12N5/0068 , C12N5/0603 , C12N5/0619 , C12N5/0696 , C12N5/0697 , C12N2501/105 , C12N2501/115 , C12N2501/12 , C12N2501/999 , C12N2506/02 , C12N2506/45 , C12N2533/50
摘要： The invention relates to culturing motor neuron cells together with skeletal muscle cells in a fluidic device under conditions whereby the interaction of these cells mimic the structure and function of the neuromuscular junction (NMJ) providing a NMJ-on-chip. Good viability, formation of myo-fibers and function of skeletal muscle cells on fluidic chips allow for measurements of muscle cell contractions. Embodiments of motor neurons co-cultures with contractile myo-fibers are contemplated for use with modeling diseases affecting NMJ's, e.g. Amyotrophic lateral sclerosis (ALS).
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公开(公告)号：US11572545B2
公开(公告)日：2023-02-07
申请号：US16310360
申请日：2017-06-16
发明人： Dhruv Sareen , Loren A. Ornelas , Clive Svendsen
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：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：US12091650B2
公开(公告)日：2024-09-17
申请号：US16286185
申请日：2019-02-26
发明人： S. Jordan Kerns , Norman Wen , Carolina Lucchesi , Christopher David Hinojosa , Jacob Fraser , Geraldine Hamilton , Gad Vatine , Samuel Sances , Clive Svendsen , Daniel Levner , Dhruv Sareen
CPC分类号： C12M23/16 , B01L3/502715 , C12M25/02 , C12N5/0068 , C12N5/0619 , C12N5/0622 , C12N5/069 , B01L2200/0647 , B01L2300/0861 , C12N2502/081 , C12N2502/28 , C12N2506/02 , C12N2506/45 , C12N2531/00 , C12N2539/00
摘要： The invention relates to culturing brain endothelial cells, and optionally astrocytes and neurons in a fluidic device under conditions whereby the cells mimic the structure and function of the blood brain barrier. Culture of such cells in a microfluidic device, whether alone or in combination with other cells, drives maturation and/or differentiation further than existing systems.
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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：US20220282221A1
公开(公告)日：2022-09-08
申请号：US17678485
申请日：2022-02-23
发明人： S. Jordan Kerns , Norman Wen , Carol Lucchesi , Christopher David Hinojosa , Jacob Fraser , Jefferson Puerta , Geraldine Hamilton , Robert Barrett , Clive Svendsen , Daniel Levner , Stephen R. Targan , Michael Workman , Dhruv Sareen , Uthra Rajamani , Magdalena Kasendra
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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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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