Science!

SpinΩ™

SpinΩ is a miniaturized, motorized, and modular system that is compatible with any standard multi-well tissue culture plates (12-well version shown). It provides a higher throughput platform to culture 3D tissues by reducing the amount of media required and promoting tissue survival. SpinΩ has proven to support the culture of human brain organoids and to be cost-effective for drug efficacy/toxicity testing. The technology was first conceptualized and developed at Johns Hopkins Institute for Cell Engineering by several talented high school student interns. 3Dnamics is further refining the bioreactor and continually inventing new tools to advance stem cell research.

Brain Organoids

Human pluripotent stem cells can be directly differentiated into region-specific brain organoids, such as cortex, midbrain, hypothalamus, medial ganglionic eminence, hippocampus, and others with high efficiency and consistency. For example, cortical organoids express forebrain-specific neuronal markers and have consistent structural organization and molecular signatures throughout different developmental stages, compared to human fetal brains. These three-dimensional (3D) organoids, which are more similar to endogenous human tissues than cells grown on monolayer, are relevant models to study disease mechanism, to perform drug/toxicity screening, and to validate specific hits obtained from a high throughput screen. Indeed, the performance of cortical organoids have been successfully tested in studies of ZIKA virus infection and validation of drug hits from a larger screen (see publications below for more details). Additionally, organoids may serve as a renewable source of cells for future regenerative medicine purposes and cell-based therapeutics.

Cortical organoid

Midbrain organoid

MGE organoid

Hippocampal organoid

Hypothalamus organoid

Alzheimer’s cortical organoid

Glioblastoma

“Mini Brains”

Disease Models

The power of pluripotent stem cells (PSCs) lies not only in their ability to become any cell types but also in their ability to recapitulate relevant disease phenotypes. Previous PSC-based studies have provided invaluable insights into underlying causes of many human disorders. 3Dnamics has developed PSC-based models for Parkinson’s, Schizophrenia, and ZIKA virus-induced microcephaly. In addition to conventional PSC-based approaches, we are also developing other disease models that can be faithfully recapitulated in 3D, such as Alzheimer’s and Glioblastoma. These disease models will serve as excellent platforms for the next generation of drug discovery and development.

Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of dementia and is often associated with aging and neurodegeneration. The two major pathological hallmarks of AD are accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Together, Aβ plaques and NFTs can lead to neuronal dysfunctions and cell death. Currently, there are no effective treatments for AD. One of the many challenges in studying and finding treatments for AD is the lack of good existing cell and animal models that can recapitulate disease phenotype. By taking alternative approaches, 3Dnamics is determined to gain a better understanding of AD pathogenensis and to combat this devastating disease, which affect millions of people worldwide. Thus, we aim to develop novel stem cell-based models and assays (conventional and 3D organoid) that can be used to unlock disease mechanism and to screen for effective compounds against AD.

Scientific Publications*
(*Representative publications from 3Dnamics’ founders)

• Qian, X., Jacob, F., Song, M.M., Nguyen, H.N., Song, H., Ming, G.L. (2018). Generation of human brain region-specific organoids using a miniaturized spinning bioreactor. Nature Protocols 13, 565-580. Read article
• Qian, X., Nguyen, H.N., Jacob, F., Song, H., Ming, G.L. (2017). Understand Zika virus-induced microcephaly using brain organoids. Development 144, 952-957.  Read article
• Nguyen, H.N., Song, H., Ming, G.L., (2016). Engineering human pluripotent stem cell-derived 3D brain tissues for drug discovery. Journal of Translational Neuroscience 1(2), 38-48. Read article
• Xu M., Lee E.M, Wen, Z., Cheng, Y., Huang, W.K., Qian, X., TWC, J., Kouznetsova, J., Ogden, S.C., Hammack, C., Jacob, F., Nguyen, H.N., Itkin, M., Hanna, C., Shinn, P., Allen, C., Michael, S.G., Simeonov, A., Huang, W., Christian, K.M., Goate, A., Brennand, K., Huang, R., Xia, M., Ming, G.L., Zheng, W., Song, H. and Tang H. (2016). Identification of small molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nature Medicine 22, 1101-1107. Read article
• Qian, X., Nguyen, H.N., Song, M.M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, G., Jacob, F., Zhong, C., Yoon, K.J., Jeang, W., Lin, L., Li, Y., Thakor, T., Berg, D.A., Zhang, C., Kang, E., Chickering, M., Nauen, D., Ho, C.Y., Wen, Z., Christian, K.M., Shi, P.Y., Maher, B.J., Wu, H. Jin, P., Tang, H., Song, H., Ming, G.L. (2016). Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. Cell 165, 1238-1254. Read article
• Wen, Z., Nguyen, H.N., Guo, Z., Lalli, M.A., Wang, X., Su, Y., Kim, N.S., Yoon, K.J., Shin, J., Zhang, C., Markri, G., Nauen, D., Yu, H., Guzman, E., Chiang, C.H., Yoritomo, N., Kaibuchi, K., Zou, J., Christian, K.M., Cheng, L., Ross, C.A., Margolis, R., Chen, G., Kosik, K.S., Song, H, Ming, G.L. (2014). Synaptic dysregulation in a human iPSC model of mental disorders. Nature 515, 414-418. Read article
• Yoon, K.J., Nguyen, H.N., Ursini, G., Zhang, F., Kim, N.S., Wen, Z., Makri, G., Shin, J.H., Park, Y., Chung, R. Pekle, E., Zhang, C., Towe, M., Hussani, Q., Lee, Y., Rujescu, D., St Clair, D., Kleinman, J.E., Hyde, T.M., Krauss, G., Christian, K.M., Rapoport, J.L, Weinberger, D.R., Song, H., and Ming, G.L. (2014). Mental disorder risk gene CYFIP1 maintains adherens junctions and polarity of human and mouse cortical neural stem cells. Cell Stem Cell 15, 79-91. Read article
• Juopperi, T.A., Kim, W.R., Chiang, C.H., Yu, H., Margolis, R.L., Ross, C.A., Ming, G.L., Song, H. (2012). Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington’s disease patient cells. Molecular Brain 5: 17. Read article
• Nguyen, H.N., Byers, B., Cord, B., Shcheglovitov, A., Byrne, J., Gujar, P., Kee, K., Schüle, B., Dolmetsch, R.E., Langston, W., Palmer, T.D., and Reijo Pera, R (2011). Lrrk2 mutant ipsc-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8, 267-280. Read article
• Batista, L. F., Pech, M. F., Zhong, F. L., Nguyen, H. N., Xie, K. T., Zaug, A. J., Crary, S. M., Choi, J., Sebastiano, V., Cherry, A., Giri, N., Wernig, M., Alter, B. P., Cech, T. R., Savage, S. A., Reijo Pera, R. A., and Artandi, S. E. (2011). Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474, 399-402. Read article
• Byers, B., Cord, B., Nguyen, H.N., Schüle, B., Fenno, L., Lee, P.C., Deisseroth, K., Langston, J.W., Reijo Pera, R., and Palmer, T.D. (2011). SNCA Triplication Parkinson’s Patient’s iPSC-derived DA Neurons Accumulate α-Synuclein and Are Susceptible to Oxidative Stress. PLoS One 6, e26159. Read article
• Rufaihah A.J., Huang N.F., Jame S., Lee J., Nguyen H.N., Byers B., De A., Okogbaa J., Rollins M., Reijo-Pera R., Gambhir S.S., and Cooke J.P. (2011). Endothelial cells derived from human iPSCs increase capillary density and improve perfusion in a mouse model of peripheral arterial disease. Arterioscler Thromb Vasc Biol. 31, e72-e79. Read article
• Panula, S., Medrano, J.V., Kee, K., Bergstrom, R., Nguyen, H.N., Byers, B., Wilson, K.D., Wu, J.C., Simon, C., Hovatta, O., and Reijo Pera, R.A. (2011). Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. Hum Mol Genet. 20, 752-762. Read article
• Byrne, J.A., Nguyen, H.N., and Reijo Pera, R.A. (2009). Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts. PLoS One 4, e7118. Read article
• Kossack, N., Meneses, J., Shefi, S., Nguyen, H.N., Chavez, S., Nicholas, C., Gromoll, J., Turek, P.J., and Reijo-Pera, R.A. (2009). Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells 27, 138-149. Read article
• Chavez, S.L., Meneses, J.J., Nguyen, H.N., Kim, S.K., and Pera, R.A. (2008). Characterization of Six New Human Embryonic Stem Cell Lines (HSF7, -8, -9, -10, -12, and -13) Derived Under Minimal-Animal Component Conditions. Stem Cells and Dev. 17, 535-546. Read article