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  1. Article: Combined 3D bioprinting and tissue-specific ECM system reveals the influence of brain matrix on stem cell differentiation.

    Zamponi, Martina / Mollica, Peter A / Khodour, Yara / Bjerring, Julie S / Bruno, Robert D / Sachs, Patrick C

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1258993

    Abstract: We have previously shown that human and murine breast extracellular matrix (ECM) can significantly impact cellular behavior, including stem cell fate determination. It has been established that tissue-specific extracellular matrix from the central ... ...

    Abstract We have previously shown that human and murine breast extracellular matrix (ECM) can significantly impact cellular behavior, including stem cell fate determination. It has been established that tissue-specific extracellular matrix from the central nervous system has the capacity to support neuronal survival. However, the characterization of its influence on stem cell differentiation and its adaptation to robust 3D culture models is underdeveloped. To address these issues, we combined our 3D bioprinter with hydrogels containing porcine brain extracellular matrix (BMX) to test the influence of the extracellular matrix on stem cell differentiation. Our 3D bioprinting system generated reproducible 3D neural structures derived from mouse embryonic stem cells (mESCs). We demonstrate that the addition of BMX preferentially influences 3D bioprinted mESCs towards neural lineages compared to standard basement membrane (Geltrex/Matrigel) hydrogels alone. Furthermore, we demonstrate that we can transplant these 3D bioprinted neural cellular structures into a mouse's cleared mammary fat pad, where they continue to grow into larger neural outgrowths. Finally, we demonstrate that direct injection of human induced pluripotent stem cells (hiPSCS) and neural stem cells (NSCs) suspended in pure BMX formed neural structures
    Language English
    Publishing date 2023-10-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1258993
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Salivary microRNA as a prospective tool for concussion diagnosis and management: A scoping review.

    Campbell, Thomas R / Reilly, Nicholas / Zamponi, Martina / Leathers, Delaney / Mollica, Peter A / Cavallario, Julie / Martinez, Jessica C

    Brain injury

    2023  Volume 37, Issue 7, Page(s) 588–595

    Abstract: Background: Despite increased efforts directed toward research, concussions are a growing concern and can be a complex injury for healthcare professionals to manage. Current practices are largely dependent on patients self-reporting symptoms and a ... ...

    Abstract Background: Despite increased efforts directed toward research, concussions are a growing concern and can be a complex injury for healthcare professionals to manage. Current practices are largely dependent on patients self-reporting symptoms and a clinical assessment, which uses objective tools that lack effectiveness. With the demonstrated effects of concussions, it is imperative that a more valid or reliable objective tool, like a clinical biomarker, be identified to improve outcomes. One potential biomarker that has shown promise is salivary microRNA. However, there is no objective consensus as to which microRNA offers the most clinical value regarding concussions, hence this review. Therefore, the purpose of this scoping review was to identify salivary miRNAs associated with concussions.
    Methods: Two independent reviewers performed a literature search to identify research articles. Studies using human subjects, collected salivary miRNA, and were published in English were included. Data of interest were salivary miRNA, collection timing, and relation to concussion diagnosis or management.
    Results: This paper reviews nine studies that analyzed salivary miRNA for concussion diagnosis and management.
    Conclusions: In total, the studies have identified 49 salivary miRNA that show promise in assisting with concussion practices. With continued research, the use of salivary miRNA may enhance clinicians' abilities to diagnose and manage concussions.
    MeSH term(s) Humans ; MicroRNAs ; Athletic Injuries/diagnosis ; Brain Concussion/diagnosis ; Brain Concussion/therapy ; Biomarkers
    Chemical Substances MicroRNAs ; Biomarkers
    Language English
    Publishing date 2023-03-03
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 639115-1
    ISSN 1362-301X ; 0269-9052
    ISSN (online) 1362-301X
    ISSN 0269-9052
    DOI 10.1080/02699052.2023.2184867
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: 3D bioprinter applied picosecond pulsed electric fields for targeted manipulation of proliferation and lineage specific gene expression in neural stem cells.

    Petrella, Ross A / Mollica, Peter A / Zamponi, Martina / Reid, John A / Xiao, Shu / Bruno, Robert D / Sachs, Patrick C

    Journal of neural engineering

    2018  Volume 15, Issue 5, Page(s) 56021

    Abstract: Objective: Picosecond pulse electric fields (psPEF) have the potential to elicit functional changes in mammalian cells in a non-contact manner. Such electro-manipulation of pluripotent and multipotent cells could be a tool in both neural interface and ... ...

    Abstract Objective: Picosecond pulse electric fields (psPEF) have the potential to elicit functional changes in mammalian cells in a non-contact manner. Such electro-manipulation of pluripotent and multipotent cells could be a tool in both neural interface and tissue engineering. Here, we describe the potential of psPEF in directing neural stem cells (NSCs) gene expression, metabolism, and proliferation. As a comparison mesenchymal stem cells (MSCs) were also tested.
    Approach: A psPEF electrode was anchored on a customized commercially available 3D printer, which allowed us to deliver pulses with high spatial precision and systematically control the electrode position in three-axes. When the electrodes are continuously energized and their position is shifted by the 3D printer, large numbers of cells on a surface can be exposed to a uniform psPEF. With two electric field strengths (20 and 40 kV cm
    Main results: Analysis revealed both NSCs and MSCs showed no significant cell death after treatments. Both cell types exhibited an increased metabolic reduction; however, the response rate for MSCs was sensitive to the change of electric field strength, but for NSCs, it appeared independent of electric field strength. The change in proliferation rate was cell-type specific. MSCs underwent no significant change in proliferation whereas NSCs exhibited an electric field dependent response with the higher electric field producing less proliferation. Further, NSCs showed an upregulation of glial fibrillary acidic protein (GFAP) after 24 h to 40 kV cm
    Significance: Changes in cell metabolism, proliferation, and gene expression after picosecond pulsed electric field exposure are cell type specific.
    MeSH term(s) Astrocytes/metabolism ; Cell Death ; Cell Lineage/genetics ; Cell Proliferation ; Electrodes ; Electromagnetic Fields ; Gene Expression/genetics ; Glial Fibrillary Acidic Protein/biosynthesis ; Glial Fibrillary Acidic Protein/genetics ; Humans ; Induced Pluripotent Stem Cells ; Mesenchymal Stem Cells ; Neural Stem Cells/physiology ; Neurogenesis ; Printing, Three-Dimensional
    Chemical Substances GFAP protein, human ; Glial Fibrillary Acidic Protein
    Language English
    Publishing date 2018-05-31
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2170901-4
    ISSN 1741-2552 ; 1741-2560
    ISSN (online) 1741-2552
    ISSN 1741-2560
    DOI 10.1088/1741-2552/aac8ec
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Epigenetic alterations mediate iPSC-induced normalization of DNA repair gene expression and TNR stability in Huntington's disease cells.

    Mollica, Peter A / Zamponi, Martina / Reid, John A / Sharma, Deepak K / White, Alyson E / Ogle, Roy C / Bruno, Robert D / Sachs, Patrick C

    Journal of cell science

    2018  Volume 131, Issue 13

    Abstract: Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat (TNR) expansion within ... ...

    Abstract Huntington's disease (HD) is a rare autosomal dominant neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat (TNR) expansion within the
    MeSH term(s) DNA Methylation ; DNA Repair ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic ; Humans ; Huntingtin Protein/genetics ; Huntingtin Protein/metabolism ; Huntington Disease/genetics ; Huntington Disease/metabolism ; Induced Pluripotent Stem Cells/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Mixed Function Oxygenases/genetics ; Mixed Function Oxygenases/metabolism ; Neural Stem Cells/metabolism ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Trinucleotide Repeat Expansion
    Chemical Substances DNA-Binding Proteins ; Huntingtin Protein ; MIRN29a microRNA, human ; MicroRNAs ; Proto-Oncogene Proteins ; Mixed Function Oxygenases (EC 1.-) ; TET1 protein, human (EC 1.-) ; TET2 protein, human (EC 1.13.11.-)
    Language English
    Publishing date 2018-07-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.215343
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: 3D bioprinted mammary organoids and tumoroids in human mammary derived ECM hydrogels.

    Mollica, Peter A / Booth-Creech, Elizabeth N / Reid, John A / Zamponi, Martina / Sullivan, Shea M / Palmer, Xavier-Lewis / Sachs, Patrick C / Bruno, Robert D

    Acta biomaterialia

    2019  Volume 95, Page(s) 201–213

    Abstract: The extracellular matrix (ECM) of tissues is an important mediator of cell function. Moreover, understanding cellular dynamics within their specific tissue context is also important for developmental biology, cancer research, and regenerative medicine. ... ...

    Abstract The extracellular matrix (ECM) of tissues is an important mediator of cell function. Moreover, understanding cellular dynamics within their specific tissue context is also important for developmental biology, cancer research, and regenerative medicine. However, robust in vitro models that incorporate tissue-specific microenvironments are lacking. Here we describe a novel mammary-specific culture protocol that combines a self-gelling hydrogel comprised solely of ECM from decellularized rat or human breast tissue with the use of our previously described 3D bioprinting platform. We initially demonstrate that undigested and decellularized mammary tissue can support mammary epithelial and tumor cell growth. We then describe a methodology for generating mammary ECM extracts that can spontaneously gel to form hydrogels. These ECM hydrogels retain unique structural and signaling profiles that elicit differential responses when normal mammary and breast cancer cells are cultured within them. Using our bioprinter, we establish that we can generate large organoids/tumoroids in the all mammary-derived hydrogel. These findings demonstrate that our system allows for growth of organoids/tumoroids in a tissue-specific matrix with unique properties, thus providing a suitable platform for ECM and epithelial/cancer cell studies. STATEMENT OF SIGNIFICANCE: Factors within extracellular matrices (ECMs) are specific to their tissue of origin. It has been shown that tissue specific factors within the mammary gland's ECM have pronounced effects on cellular differentiation and cancer behavior. Understanding the role of the ECM in controlling cell fate has major implications for developmental biology, tissue engineering, and cancer therapy. However, in vitro models to study cellular interactions with tissue specific ECM are lacking. Here we describe the generation of 3D hydrogels consisting solely of human or mouse mammary ECM. We demonstrate that these novel 3D culture substrates can sustain large 3D bioprinted organoid and tumoroid formation. This is the first demonstration of an all mammary ECM culture system capable of sustaining large structural growths.
    MeSH term(s) Animals ; Bioprinting ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Extracellular Matrix/chemistry ; Female ; Humans ; Hydrogels/pharmacology ; Intercellular Signaling Peptides and Proteins/metabolism ; Keratin-5/metabolism ; Ki-67 Antigen/metabolism ; Mammary Glands, Human/pathology ; Organoids/metabolism ; Printing, Three-Dimensional ; Rats ; Signal Transduction
    Chemical Substances Hydrogels ; Intercellular Signaling Peptides and Proteins ; Keratin-5 ; Ki-67 Antigen
    Language English
    Publishing date 2019-06-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2019.06.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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