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  1. Article ; Online: Plasticity of muscle stem cells in homeostasis and aging.

    Porpiglia, Ermelinda / Blau, Helen M

    Current opinion in genetics & development

    2022  Volume 77, Page(s) 101999

    Abstract: We are living longer, but our healthspan has not increased. The goal of regenerative medicine is to increase quality of life through an understanding of the cellular and molecular processes that underlie effective tissue repair in order to restore ... ...

    Abstract We are living longer, but our healthspan has not increased. The goal of regenerative medicine is to increase quality of life through an understanding of the cellular and molecular processes that underlie effective tissue repair in order to restore damaged tissues. The drivers of muscle regeneration are the muscle stem cells that cycle between quiescent and activated states to meet tissue regenerative demands. Here we review recent findings on the role of the niche, or tissue microenvironment, in the modulation of muscle stem cell plasticity and the mechanisms responsible for the drastic loss of stem cell function with aging. These new studies unveil fundamental mechanisms of stem cell plasticity with broad relevance to other tissues and lay the foundation for the development of therapeutic strategies to boost the regenerative potential of aged muscle stem cells.
    MeSH term(s) Quality of Life ; Homeostasis/genetics ; Stem Cells/physiology ; Muscles ; Muscle, Skeletal
    Language English
    Publishing date 2022-10-26
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2022.101999
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reversing aging for heart repair.

    Wang, Yu Xin / Blau, Helen M

    Science (New York, N.Y.)

    2021  Volume 373, Issue 6562, Page(s) 1439–1440

    Abstract: Short-term induction of pluripotency gene expression allows adult mouse cardiomyocytes to regenerate. ...

    Abstract Short-term induction of pluripotency gene expression allows adult mouse cardiomyocytes to regenerate.
    Language English
    Publishing date 2021-09-23
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abl8679
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tissue Stem Cells: Architects of Their Niches.

    Fuchs, Elaine / Blau, Helen M

    Cell stem cell

    2020  Volume 27, Issue 4, Page(s) 532–556

    Abstract: Stem cells (SCs) maintain tissue homeostasis and repair wounds. Despite marked variation in tissue architecture and regenerative demands, SCs often follow similar paradigms in communicating with their microenvironmental "niche" to transition between ... ...

    Abstract Stem cells (SCs) maintain tissue homeostasis and repair wounds. Despite marked variation in tissue architecture and regenerative demands, SCs often follow similar paradigms in communicating with their microenvironmental "niche" to transition between quiescent and regenerative states. Here we use skin epithelium and skeletal muscle-among the most highly-stressed tissues in our body-to highlight similarities and differences in niche constituents and how SCs mediate natural tissue rejuvenation and perform regenerative acts prompted by injuries. We discuss how these communication networks break down during aging and how understanding tissue SCs has led to major advances in regenerative medicine.
    MeSH term(s) Muscle, Skeletal ; Regenerative Medicine ; Rejuvenation ; Stem Cells
    Language English
    Publishing date 2020-09-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2020.09.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Stem Cells in the Treatment of Disease.

    Blau, Helen M / Daley, George Q

    The New England journal of medicine

    2019  Volume 380, Issue 18, Page(s) 1748–1760

    MeSH term(s) Animals ; Cardiomyopathies/therapy ; Combined Modality Therapy ; Epidermolysis Bullosa/therapy ; Genetic Therapy ; Humans ; Induced Pluripotent Stem Cells/transplantation ; Macular Degeneration/therapy ; Muscular Dystrophy, Duchenne/therapy ; Stem Cell Transplantation ; Stem Cells
    Language English
    Publishing date 2019-05-01
    Publishing country United States
    Document type Journal Article ; Review ; Video-Audio Media
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMra1716145
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sir John Gurdon: father of nuclear reprogramming.

    Blau, Helen M

    Differentiation; research in biological diversity

    2014  Volume 88, Issue 1, Page(s) 10–12

    Abstract: Sir John Gurdon founded the field of nuclear reprogramming. His work set the stage for the ever burgeoning area of stem cell biology and regenerative medicine. Here I provide personal reflections on times I shared with John Gurdon and professional ... ...

    Abstract Sir John Gurdon founded the field of nuclear reprogramming. His work set the stage for the ever burgeoning area of stem cell biology and regenerative medicine. Here I provide personal reflections on times I shared with John Gurdon and professional reflections of the impact of his ground-breaking research on my own development as a scientist and on the field in general. His paradigm-shifting experiments will continue to provoke scientists to think outside the box for many years to come.
    MeSH term(s) Cellular Reprogramming ; History, 20th Century ; History, 21st Century ; Regenerative Medicine
    Language English
    Publishing date 2014-06-18
    Publishing country England
    Document type Biography ; Historical Article ; Journal Article
    ZDB-ID 184540-8
    ISSN 1432-0436 ; 0301-4681
    ISSN (online) 1432-0436
    ISSN 0301-4681
    DOI 10.1016/j.diff.2014.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Macrophages rescue injured engineered muscle.

    Wang, Yu Xin / Blau, Helen M

    Nature biomedical engineering

    2018  Volume 2, Issue 12, Page(s) 890–891

    Language English
    Publishing date 2018-10-29
    Publishing country England
    Document type Journal Article ; Comment
    ISSN 2157-846X
    ISSN (online) 2157-846X
    DOI 10.1038/s41551-018-0312-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Tamoxifen treatment ameliorates contractile dysfunction of Duchenne muscular dystrophy stem cell-derived cardiomyocytes on bioengineered substrates.

    Birnbaum, Foster / Eguchi, Asuka / Pardon, Gaspard / Chang, Alex C Y / Blau, Helen M

    NPJ Regenerative medicine

    2022  Volume 7, Issue 1, Page(s) 19

    Abstract: Duchenne muscular dystrophy (DMD) is a progressive genetic myopathy that leads to heart failure from dilated cardiomyopathy by early adulthood. Recent evidence suggests that tamoxifen, a selective estrogen receptor modulator widely used to treat breast ... ...

    Abstract Duchenne muscular dystrophy (DMD) is a progressive genetic myopathy that leads to heart failure from dilated cardiomyopathy by early adulthood. Recent evidence suggests that tamoxifen, a selective estrogen receptor modulator widely used to treat breast cancer, ameliorates DMD cardiomyopathy. However, the mechanism of action of 4-hydroxytamoxifen, the active metabolite of tamoxifen, on cardiomyocyte function remains unclear. To examine the effects of chronic 4-hydroxytamoxifen treatment, we used state-of-the-art human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and a bioengineered platform to model DMD. We assessed the beating rate and beating velocity of iPSC-CMs in monolayers and as single cells on micropatterns that promote a physiological cardiomyocyte morphology. We found that 4-hydroxytamoxifen treatment of DMD iPSC-CMs decreased beating rate, increased beating velocity, and ameliorated calcium-handling deficits, leading to prolonged viability. Our study highlights the utility of a bioengineered iPSC-CM platform for drug testing and underscores the potential of repurposing tamoxifen as a therapy for DMD cardiomyopathy.
    Language English
    Publishing date 2022-03-18
    Publishing country United States
    Document type Journal Article
    ISSN 2057-3995
    ISSN (online) 2057-3995
    DOI 10.1038/s41536-022-00214-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Redefining differentiation: Reshaping our ends.

    Blau, Helen M

    Nature cell biology

    2012  Volume 14, Issue 6, Page(s) 558

    MeSH term(s) Animals ; Cell Differentiation ; Cell Lineage ; Cellular Reprogramming ; Humans ; Stem Cells/cytology ; Stem Cells/metabolism
    Language English
    Publishing date 2012-05-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 1474722-4
    ISSN 1476-4679 ; 1465-7392
    ISSN (online) 1476-4679
    ISSN 1465-7392
    DOI 10.1038/ncb2506
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Biophysical matrix cues from the regenerating niche direct muscle stem cell fate in engineered microenvironments.

    Madl, Christopher M / Flaig, Iris A / Holbrook, Colin A / Wang, Yu Xin / Blau, Helen M

    Biomaterials

    2021  Volume 275, Page(s) 120973

    Abstract: Skeletal muscle stem cells (MuSCs) are essential for efficacious muscle repair, making MuSCs promising therapeutic targets for tissue engineering and regenerative medicine. MuSCs are presented with a diverse and temporally defined set of cues from their ... ...

    Abstract Skeletal muscle stem cells (MuSCs) are essential for efficacious muscle repair, making MuSCs promising therapeutic targets for tissue engineering and regenerative medicine. MuSCs are presented with a diverse and temporally defined set of cues from their microenvironment during regeneration that direct stem cell expansion, differentiation, and return to quiescence. Understanding the complex interplay among these biophysical and biochemical cues is necessary to develop therapies targeting or employing MuSCs. To probe the role of mechanical cues presented by the extracellular matrix, we leverage chemically defined hydrogel substrates with controllable stiffness and adhesive ligand composition to characterize the MuSC response to matrix cues presented during early and late phases of regeneration. We demonstrate that relatively soft hydrogels recapitulating healthy muscle stiffness promote MuSC activation and expansion, while relatively stiff hydrogels impair MuSC proliferation and arrest myogenic progression. These effects are seen on soft and stiff hydrogels presenting laminin-111 and exacerbated on hydrogels presenting RGD adhesive peptides. Soluble factors present in the MuSC niche during different phases of regeneration, prostaglandin E2 and oncostatin M, synergize with matrix-presented cues to enhance stem cell expansion on soft substrates and block myogenic progression on stiff substrates. To determine if temporally varied matrix stiffness reminiscent of the regenerating microenvironment alters MuSC fate, we developed a photoresponsive hydrogel system with accelerated reaction kinetics that can be rapidly softened on demand. MuSCs cultured on these materials revealed that the cellular response to a stiff microenvironment is fixed within the first three days of culture, as subsequent softening back to a healthy stiffness did not rescue MuSC proliferation or myogenic progression. These results highlight the importance of temporally controlled biophysical and biochemical cues in regulating MuSC fate that can be harnessed to improve regenerative medicine approaches to restore skeletal muscle tissue.
    MeSH term(s) Cell Differentiation ; Cues ; Hydrogels ; Muscle Development ; Muscle, Skeletal ; Myoblasts ; Regeneration ; Stem Cell Niche
    Chemical Substances Hydrogels
    Language English
    Publishing date 2021-06-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2021.120973
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Bioengineering strategies to accelerate stem cell therapeutics.

    Madl, Christopher M / Heilshorn, Sarah C / Blau, Helen M

    Nature

    2018  Volume 557, Issue 7705, Page(s) 335–342

    Abstract: Although only a few stem cell-based therapies are currently available to patients, stem cells hold tremendous regenerative potential, and several exciting clinical applications are on the horizon. Biomaterials with tuneable mechanical and biochemical ... ...

    Abstract Although only a few stem cell-based therapies are currently available to patients, stem cells hold tremendous regenerative potential, and several exciting clinical applications are on the horizon. Biomaterials with tuneable mechanical and biochemical properties can preserve stem cell function in culture, enhance survival of transplanted cells and guide tissue regeneration. Rapid progress with three-dimensional hydrogel culture platforms provides the opportunity to grow patient-specific organoids, and has led to the discovery of drugs that stimulate endogenous tissue-specific stem cells and enabled screens for drugs to treat disease. Therefore, bioengineering technologies are poised to overcome current bottlenecks and revolutionize the field of regenerative medicine.
    MeSH term(s) Animals ; Bioengineering/methods ; Bioengineering/trends ; Cell Differentiation ; Cell Lineage ; Humans ; Regenerative Medicine/methods ; Regenerative Medicine/trends ; Stem Cell Transplantation/methods ; Stem Cell Transplantation/trends ; Stem Cells/cytology
    Language English
    Publishing date 2018-05-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-018-0089-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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