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6. Rapid tissue prototyping with micro-organospheres

Author

Wang, Zhaohui, primary, Boretto, Matteo, additional, Millen, Rosemary, additional, Natesh, Naveen, additional, Reckzeh, Elena S., additional, Hsu, Carolyn, additional, Negrete, Marcos, additional, Yao, Haipei, additional, Quayle, William, additional, Heaton, Brook E., additional, Harding, Alfred T., additional, Bose, Shree, additional, Driehuis, Else, additional, Beumer, Joep, additional, Rivera, Grecia O., additional, van Ineveld, Ravian L., additional, Gex, Donald, additional, DeVilla, Jessica, additional, Wang, Daisong, additional, Puschhof, Jens, additional, Geurts, Maarten H., additional, Yeung, Athena, additional, Hamele, Cait, additional, Smith, Amber, additional, Bankaitis, Eric, additional, Xiang, Kun, additional, Ding, Shengli, additional, Nelson, Daniel, additional, Delubac, Daniel, additional, Rios, Anne, additional, Abi-Hachem, Ralph, additional, Jang, David, additional, Goldstein, Bradley J., additional, Glass, Carolyn, additional, Heaton, Nicholas S., additional, Hsu, David, additional, Clevers, Hans, additional, and Shen, Xiling, additional

Published
2022
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7. Rapid tissue prototyping with micro-organospheres

Author

Wang, Zhaohui, Boretto, Matteo, Millen, Rosemary, Natesh, Naveen, Reckzeh, Elena S, Hsu, Carolyn, Negrete, Marcos, Yao, Haipei, Quayle, William, Heaton, Brook E, Harding, Alfred T, Bose, Shree, Driehuis, Else, Beumer, Joep, Rivera, Grecia O, van Ineveld, Ravian L, Gex, Donald, DeVilla, Jessica, Wang, Daisong, Puschhof, Jens, Geurts, Maarten H, Yeung, Athena, Hamele, Cait, Smith, Amber, Bankaitis, Eric, Xiang, Kun, Ding, Shengli, Nelson, Daniel, Delubac, Daniel, Rios, Anne, Abi-Hachem, Ralph, Jang, David, Goldstein, Bradley J, Glass, Carolyn, Heaton, Nicholas S, Hsu, David, Clevers, Hans, Shen, Xiling, Wang, Zhaohui, Boretto, Matteo, Millen, Rosemary, Natesh, Naveen, Reckzeh, Elena S, Hsu, Carolyn, Negrete, Marcos, Yao, Haipei, Quayle, William, Heaton, Brook E, Harding, Alfred T, Bose, Shree, Driehuis, Else, Beumer, Joep, Rivera, Grecia O, van Ineveld, Ravian L, Gex, Donald, DeVilla, Jessica, Wang, Daisong, Puschhof, Jens, Geurts, Maarten H, Yeung, Athena, Hamele, Cait, Smith, Amber, Bankaitis, Eric, Xiang, Kun, Ding, Shengli, Nelson, Daniel, Delubac, Daniel, Rios, Anne, Abi-Hachem, Ralph, Jang, David, Goldstein, Bradley J, Glass, Carolyn, Heaton, Nicholas S, Hsu, David, Clevers, Hans, and Shen, Xiling

Abstract

In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.

Published
2022

8. Rapid tissue prototyping with micro-organospheres

Author

CMM, Cancer, Hubrecht Institute with UMC, Wang, Zhaohui, Boretto, Matteo, Millen, Rosemary, Natesh, Naveen, Reckzeh, Elena S., Hsu, Carolyn, Negrete, Marcos, Yao, Haipei, Quayle, William, Heaton, Brook E., Harding, Alfred T., Bose, Shree, Driehuis, Else, Beumer, Joep, Rivera, Grecia O., van Ineveld, Ravian L., Gex, Donald, DeVilla, Jessica, Wang, Daisong, Puschhof, Jens, Geurts, Maarten H., Yeung, Athena, Hamele, Cait, Smith, Amber, Bankaitis, Eric, Xiang, Kun, Ding, Shengli, Nelson, Daniel, Delubac, Daniel, Rios, Anne, Abi-Hachem, Ralph, Jang, David, Goldstein, Bradley J., Glass, Carolyn, Heaton, Nicholas S., Hsu, David, Clevers, Hans, Shen, Xiling, CMM, Cancer, Hubrecht Institute with UMC, Wang, Zhaohui, Boretto, Matteo, Millen, Rosemary, Natesh, Naveen, Reckzeh, Elena S., Hsu, Carolyn, Negrete, Marcos, Yao, Haipei, Quayle, William, Heaton, Brook E., Harding, Alfred T., Bose, Shree, Driehuis, Else, Beumer, Joep, Rivera, Grecia O., van Ineveld, Ravian L., Gex, Donald, DeVilla, Jessica, Wang, Daisong, Puschhof, Jens, Geurts, Maarten H., Yeung, Athena, Hamele, Cait, Smith, Amber, Bankaitis, Eric, Xiang, Kun, Ding, Shengli, Nelson, Daniel, Delubac, Daniel, Rios, Anne, Abi-Hachem, Ralph, Jang, David, Goldstein, Bradley J., Glass, Carolyn, Heaton, Nicholas S., Hsu, David, Clevers, Hans, and Shen, Xiling

Published
2022

18. BMP7 antagonizes proliferative vitreoretinopathy through retinal pigment epithelial fibrosis in vivo and in vitro.

Author

Yao H, Ge T, Zhang Y, Li M, Yang S, Li H, and Wang F

Subjects
Animals, Bone Morphogenetic Protein 7 genetics, Bone Morphogenetic Protein 7 pharmacology, Cell Movement, Cells, Cultured, Disease Models, Animal, Down-Regulation, Epithelial-Mesenchymal Transition, Fibrosis, Gene Knockdown Techniques, Humans, RNA, Small Interfering genetics, Rabbits, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology, Signal Transduction, Transforming Growth Factor beta2 metabolism, Vitreoretinopathy, Proliferative pathology, Vitreoretinopathy, Proliferative prevention & control, Vitreous Body metabolism, Bone Morphogenetic Protein 7 metabolism, Vitreoretinopathy, Proliferative metabolism
Abstract

The major pathogenesis of proliferative vitreoretinopathy (PVR) is that retinal pigment epithelial (RPE) cells undergo epithelial-mesenchymal transition (EMT) because of disordered growth factors, such as TGF-β, in the vitreous humor. Bone morphogenetic proteins (BMPs) are pluripotent growth factors. In this study, we identified the antifibrotic activity of BMP7 in a PVR model both in vivo and in vitro. BMP7 expression was confirmed on the PVR proliferative membranes. BMP7 was down-regulated in the PVR vitreous humor and TGF-β-induced RPE cell EMT. In the in vivo studies, BMP7 injection attenuated PVR progression in the eyes of the rabbit model. Additionally, BMP7 treatment maintained RPE cell phenotypes and relieved TGF-β2-induced EMT, migration, and gel contraction in vitro. BMP7 inhibited the TGF-β2-induced up-regulation of fibronectin and α-smooth muscle actin and the down-regulation of E-cadherin and zona occludens-1 by balancing the TGF-β2/Smad2/3 and BMP7/Smad1/5/9 pathways. These findings provide direct evidence of the ability of BMP7 in PVR inhibition and the potential of BMP7 for use in PVR therapeutic intervention.-Yao, H., Ge, T., Zhang, Y., Li, M., Yang, S., Li, H., Wang, F. BMP7 antagonizes proliferative vitreoretinopathy through retinal pigment epithelial fibrosis in vivo and in vitro.

Published
2019
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