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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
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Article ; Online: The revolution will be open-source: how 3D bioprinting can change 3D cell culture.

Bruno, Robert D / Reid, John / Sachs, Patrick C

Oncotarget

2019 Volume 10, Issue 46, Page(s) 4724–4726

Language	English
Publishing date	2019-07-30
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.27099
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Article ; Online: Correction to: Consistent and reproducible cultures of large-scale 3D mammary epithelial structures using an accessible bioprinting platform.

Reid, John A / Mollica, Peter A / Bruno, Robert D / Sachs, Patrick C

Breast cancer research : BCR

2018 Volume 20, Issue 1, Page(s) 136

Abstract: Following publication of the original article [1], the authors reported a typesetting error in the spelling of the second author's name. ...

Abstract	Following publication of the original article [1], the authors reported a typesetting error in the spelling of the second author's name.
Language	English
Publishing date	2018-11-19
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-018-1069-9
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Article: Tissue specific microenvironments: a key tool for tissue engineering and regenerative medicine.

Sachs, Patrick C / Mollica, Peter A / Bruno, Robert D

Journal of biological engineering

2017 Volume 11, Page(s) 34

Abstract: The accumulated evidence points to the microenvironment as the primary mediator of cellular fate determination. Comprised of parenchymal cells, stromal cells, structural extracellular matrix proteins, and signaling molecules, the microenvironment is a ... ...

Abstract	The accumulated evidence points to the microenvironment as the primary mediator of cellular fate determination. Comprised of parenchymal cells, stromal cells, structural extracellular matrix proteins, and signaling molecules, the microenvironment is a complex and synergistic edifice that varies tissue to tissue. Furthermore, it has become increasingly clear that the microenvironment plays crucial roles in the establishment and progression of diseases such as cardiovascular disease, neurodegeneration, cancer, and ageing. Here we review the historical perspectives on the microenvironment, and how it has directed current explorations in tissue engineering. By thoroughly understanding the role of the microenvironment, we can begin to correctly manipulate it to prevent and cure diseases through regenerative medicine techniques.
Language	English
Publishing date	2017-11-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2391582-1
ISSN	1754-1611
ISSN	1754-1611
DOI	10.1186/s13036-017-0077-0
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Article ; Online: Consistent and reproducible cultures of large-scale 3D mammary epithelial structures using an accessible bioprinting platform.

Reid, John A / Mollica, Peter A / Bruno, Robert D / Sachs, Patrick C

Breast cancer research : BCR

2018 Volume 20, Issue 1, Page(s) 122

Abstract: Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, ... ...

Abstract	Background: Standard three-dimensional (3D) in vitro culture techniques, such as those used for mammary epithelial cells, rely on random distribution of cells within hydrogels. Although these systems offer advantages over traditional 2D models, limitations persist owing to the lack of control over cellular placement within the hydrogel. This results in experimental inconsistencies and random organoid morphology. Robust, high-throughput experimentation requires greater standardization of 3D epithelial culture techniques. Methods: Here, we detail the use of a 3D bioprinting platform as an investigative tool to control the 3D formation of organoids through the "self-assembly" of human mammary epithelial cells. Experimental bioprinting procedures were optimized to enable the formation of controlled arrays of individual mammary organoids. We define the distance and cell number parameters necessary to print individual organoids that do not interact between print locations as well as those required to generate large contiguous organoids connected through multiple print locations. Results: We demonstrate that as few as 10 cells can be used to form 3D mammary structures in a single print and that prints up to 500 μm apart can fuse to form single large structures. Using these fusion parameters, we demonstrate that both linear and non-linear (contiguous circles) can be generated with sizes of 3 mm in length/diameter. We confirm that cells from individual prints interact to form structures with a contiguous lumen. Finally, we demonstrate that organoids can be printed into human collagen hydrogels, allowing for all-human 3D culture systems. Conclusions: Our platform is adaptable to different culturing protocols and is superior to traditional random 3D culture techniques in efficiency, reproducibility, and scalability. Importantly, owing to the low-cost accessibility and computer numerical control-driven platform of our 3D bioprinter, we have the ability to disseminate our experiments with absolute precision to interested laboratories.
MeSH term(s)	Bioprinting/methods ; Cell Culture Techniques/methods ; Cell Line ; Epithelial Cells/cytology ; Female ; Humans ; Hydrogels ; Mammary Glands, Human/cytology ; Organoids/cytology ; Organoids/growth & development ; Reproducibility of Results
Chemical Substances	Hydrogels
Language	English
Publishing date	2018-10-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-018-1045-4
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Brain topography on adult ultrasound images: Techniques, interpretation, and image library.

Kapoor, Sahil / Offnick, Austin / Allen, Beddome / Brown, Patrick A / Sachs, Jeffrey R / Gurcan, Metin Nafi / Pinton, Gianmarco / D'Agostino, Ralph / Bushnell, Cheryl / Wolfe, Stacey / Duncan, Pam / Asimos, Andrew / Sarwal, Aarti

Journal of neuroimaging : official journal of the American Society of Neuroimaging

2022 Volume 32, Issue 6, Page(s) 1013–1026

Abstract: ... skull. Two investigators underwent hands-on training in Cranial point-of-care ultrasound (c-POCUS) and ... reproducible structures visible on c-POCUS included bony parts and parenchymal structures. Transcranial and ...

Abstract	Background and purpose: Many studies have explored the possibility of using cranial ultrasound for discerning intracranial pathologies like tumors, hemorrhagic stroke, or subdural hemorrhage in clinical scenarios where computer tomography may not be accessible or feasible. The visualization of intracranial anatomy on B-mode ultrasound is challenging due to the presence of the skull that limits insonation to a few segments on the temporal bone that are thin enough to allow transcranial transmission of sound. Several artifacts are produced by hyperechoic signals inherent in brain and skull anatomy when images are created using temporal windows. Methods: While the literature has investigated the accuracy of diagnosis of intracranial pathology with ultrasound, we lack a reference source for images acquired on cranial topography on B-mode ultrasound to illustrate the appearance of normal and abnormal structures of the brain and skull. Two investigators underwent hands-on training in Cranial point-of-care ultrasound (c-POCUS) and acquired multiple images from each patient to obtain the most in-depth images of brain to investigate all visible anatomical structures and pathology within 24 hours of any CT/MRI imaging done. Results: Most reproducible structures visible on c-POCUS included bony parts and parenchymal structures. Transcranial and abdominal presets were equivalent in elucidating anatomical structures. Brain pathology like parenchymal hemorrhage, cerebral edema, and hydrocephalus were also visualized. Conclusions: We present an illustrated anatomical atlas of cranial ultrasound B-mode images acquired in various pathologies in a critical care environment and compare our findings with published literature by performing a scoping review of literature on the subject.
MeSH term(s)	Adult ; Humans ; Brain/diagnostic imaging ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; Echoencephalography ; Temporal Bone
Language	English
Publishing date	2022-08-04
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	1071724-9
ISSN	1552-6569 ; 1051-2284
ISSN (online)	1552-6569
ISSN	1051-2284
DOI	10.1111/jon.13031
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Zs.A 3211: Show issues

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Article ; Online: Tissue specific microenvironments

Patrick C. Sachs / Peter A. Mollica / Robert D. Bruno

Journal of Biological Engineering, Vol 11, Iss 1, Pp 1-

a key tool for tissue engineering and regenerative medicine

2017 Volume 11

Abstract: Abstract The accumulated evidence points to the microenvironment as the primary mediator of cellular fate determination. Comprised of parenchymal cells, stromal cells, structural extracellular matrix proteins, and signaling molecules, the ... ...

Abstract	Abstract The accumulated evidence points to the microenvironment as the primary mediator of cellular fate determination. Comprised of parenchymal cells, stromal cells, structural extracellular matrix proteins, and signaling molecules, the microenvironment is a complex and synergistic edifice that varies tissue to tissue. Furthermore, it has become increasingly clear that the microenvironment plays crucial roles in the establishment and progression of diseases such as cardiovascular disease, neurodegeneration, cancer, and ageing. Here we review the historical perspectives on the microenvironment, and how it has directed current explorations in tissue engineering. By thoroughly understanding the role of the microenvironment, we can begin to correctly manipulate it to prevent and cure diseases through regenerative medicine techniques.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: ALDH1A1 positive cells are a unique component of the tonsillar crypt niche and are lost along with NGFR positive stem cells during tumourigenesis.

Wu, Vivian / Auchman, Megan / Mollica, Peter A / Sachs, Patrick C / Bruno, Robert D

Pathology

2018 Volume 50, Issue 5, Page(s) 524–529

Abstract: Interest into the cellular biology of human tonsillar crypts has grown in recent years because it is now known to be the site of origin of most human papilloma virus (HPV) induced oropharyngeal squamous cell carcinomas (OPSCC). Despite the interest, ... ...

Abstract	Interest into the cellular biology of human tonsillar crypts has grown in recent years because it is now known to be the site of origin of most human papilloma virus (HPV) induced oropharyngeal squamous cell carcinomas (OPSCC). Despite the interest, still relatively little is known regarding the cellular hierarchy and dynamics of this anatomical subsite. Here we evaluate normal tonsillar crypts for expression of putative stem cell markers. We found that ALDH1A1 was uniquely expressed in a subset of suprabasal tonsillar crypt epithelium. This cell population was unique from NGFR expressing cells, which were previously identified to have stem/progenitor activity in vitro. In vivo mitochondrial lineage tracing was consistent with a basal to luminal progression of cellular development. This provides support for NGFR cells as the resident stem/progenitor cells in tonsillar crypts, and suggests that the ALDH1A1 cells are not stem/progenitor cells, but merely a unique component of the crypt cellular microenvironment. Analysis of tumours found that both NGFR and ALDH1A1 are lost in HPV+ and HPV- tumours, while LGR5 expression is induced in the same tumours. These results identify a unique component of the tonsillar crypt epithelium-ALDH1A1 cells-and support a cellular model where NGFR+ cells are the long-lived progenitor cells within tonsillar crypts. They also provide evidence that NGFR and ALDH1A1+ cells are lost during tumourigenesis.
MeSH term(s)	Aldehyde Dehydrogenase/genetics ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Differentiation/physiology ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/pathology ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/pathology ; Humans ; Nerve Tissue Proteins/genetics ; Palatine Tonsil/metabolism ; Papillomavirus Infections/pathology ; Receptors, Nerve Growth Factor/genetics ; Squamous Cell Carcinoma of Head and Neck
Chemical Substances	NGFR protein, human ; Nerve Tissue Proteins ; Receptors, Nerve Growth Factor ; ALDH1A1 protein, human (EC 1.2.1.3) ; Aldehyde Dehydrogenase (EC 1.2.1.3)
Language	English
Publishing date	2018-06-08
Publishing country	England
Document type	Journal Article
ZDB-ID	7085-3
ISSN	1465-3931 ; 0031-3025
ISSN (online)	1465-3931
ISSN	0031-3025
DOI	10.1016/j.pathol.2018.03.002
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Zs.A 723: Show issues

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Article ; Online: Choledochal Cyst or Benign Biliary Dilation: Is Resection Always Necessary?

Gomes, Camilla / Tivnan, Patrick / McAneny, David / Tseng, Jennifer F / Tkacz, Jaroslaw / Sachs, Teviah E

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

2021 Volume 25, Issue 9, Page(s) 2353–2357

Abstract: Background: Choledochal cysts (CC) are often diagnosed during the first few decades of life, when, due to the risk of malignancy, resection is advised. With an increasing number of patients undergoing abdominal imaging, many older patients have recently ...

Abstract	Background: Choledochal cysts (CC) are often diagnosed during the first few decades of life, when, due to the risk of malignancy, resection is advised. With an increasing number of patients undergoing abdominal imaging, many older patients have recently been radiographically diagnosed with biliary duct enlargement that meets the criteria of choledochal cysts. The management in these patients is less well defined, but resection is often recommended as it is for younger patients. We sought to better understand the significance of these biliary duct anomalies in adults. Methods: We retrospectively reviewed all patients 18 years and older at our institution, who were given a radiographic diagnosis of choledochal cyst during the interval 2006-2019. Demographics, comorbidities, complications, readmissions, and follow-up imaging were evaluated. Results: We identified 22 patients, of whom 40.9% (n = 9) underwent an operation. The remainder was observed. Median duct size was 15 mm (range 2-25 mm). There were no significant differences in demographics between the two cohorts. Of those who underwent resection, none had evidence of high-grade dysplasia or invasive carcinoma upon final pathology. However, 33.3% (n = 3) had subsequent readmissions for complications, including post-operative nausea and vomiting, cholangitis, and anastomotic stenoses that required stenting. In the observation group, there was no obvious growth of the cysts or development of worrisome features to suggest malignant degeneration (median follow-up = 68 months). Conclusion: A radiographic diagnosis of choledochal cyst in older adults is likely a different entity than those diagnosed in childhood. Close surveillance of these biliary duct anomalies in older adults may be a better option than resection and reconstruction with the associated risks of long-term morbidity.
MeSH term(s)	Aged ; Cholangitis ; Choledochal Cyst/diagnostic imaging ; Choledochal Cyst/surgery ; Dilatation ; Humans ; Retrospective Studies ; Vomiting
Language	English
Publishing date	2021-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2012365-6
ISSN	1873-4626 ; 1934-3213 ; 1091-255X
ISSN (online)	1873-4626 ; 1934-3213
ISSN	1091-255X
DOI	10.1007/s11605-020-04896-w
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Zs.A 5207: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 354: Show issues

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Article ; Online: A 3D bioprinter platform for mechanistic analysis of tumoroids and chimeric mammary organoids.

Reid, John A / Palmer, Xavier-Lewis / Mollica, Peter A / Northam, Nicole / Sachs, Patrick C / Bruno, Robert D

Scientific reports

2019 Volume 9, Issue 1, Page(s) 7466

Abstract: The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, ...

Abstract	The normal mammary microenvironment can suppress tumorigenesis and redirect cancer cells to adopt a normal mammary epithelial cell fate in vivo. Understanding of this phenomenon offers great promise for novel treatment and detection strategies in cancer, but current model systems make mechanistic insights into the process difficult. We have recently described a low-cost bioprinting platform designed to be accessible for basic cell biology laboratories. Here we report the use of this system for the study of tumorigenesis and microenvironmental redirection of breast cancer cells. We show our bioprinter significantly increases tumoroid formation in 3D collagen gels and allows for precise generation of tumoroid arrays. We also demonstrate that we can mimic published in vivo findings by co-printing cancer cells along with normal mammary epithelial cells to generate chimeric organoids. These chimeric organoids contain cancer cells that take part in normal luminal formation. Furthermore, we show for the first time that cancer cells within chimeric structures have a significant increase in 5-hydroxymethylcytosine levels as compared to bioprinted tumoroids. These results demonstrate the capacity of our 3D bioprinting platform to study tumorigenesis and microenvironmental control of breast cancer and highlight a novel mechanistic insight into the process of microenvironmental control of cancer.
MeSH term(s)	5-Methylcytosine/analogs & derivatives ; 5-Methylcytosine/metabolism ; Biotechnology/methods ; Breast Neoplasms/pathology ; Carcinogenesis/pathology ; Cell Line ; Cells, Cultured ; Female ; Humans ; MCF-7 Cells ; Mammary Glands, Human/cytology ; Mammary Glands, Human/pathology ; Organoids/metabolism ; Organoids/pathology ; Printing, Three-Dimensional ; Tumor Microenvironment
Chemical Substances	5-hydroxymethylcytosine (1123-95-1) ; 5-Methylcytosine (6R795CQT4H)
Language	English
Publishing date	2019-05-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-43922-z
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