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Animal models predominate the field of drug testing and discovery, despite a growing body of evidence suggesting that such models are often poor predictors of human reactions. As a postdoctoral researcher at the University of Lausanne in Switzerland, Dr. David Pamies is working on something which might help to address these shortcomings: a human-induced pluripotent stem cell-derived 3D platform, and the development of a brain organoid—an in vitro model representing the human brain.

He and his team are using the model to predict the toxicity of many different chemicals that we encounter on a daily basis. In addition to providing a cheaper and more efficient way of studying this than the industry standard of mouse models, this model is allowing Dr. Pamies to study the effectiveness of pharmaceuticals such as temozolomide in glioblastoma, a type of brain cancer also referred to as glioblastoma multiforme (GBM).

He explains how they transplant and incorporate glioblastoma tumors from humans into the model, what they’ve learned so far in doing so, and the current issues they’re working on. He also discusses the nature of his most recent research and where it’s headed in the future.

Tune in to hear the full conversation.

Here are different publications related to Organoids and Human Brain:

Organanoids, 3D cultures.

  • Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. Cerebral organoids model human brain development and microcephaly. Nature. 2013 Sep 19;501(7467):373-9. doi: 10.1038/nature12517.
  • Pamies D, Barreras P, Block K, Makri G, Kumar A, Wiersma D, Smirnova L, Zang C, Bressler J, Christian KM, Harris G, Ming GL, Berlinicke CJ, Kyro K, Song H, Pardo CA, Hartung T, Hogberg HT. A human brain microphysiological system derived  from induced pluripotent stem cells to study neurological diseases and toxicity.  ALTEX. 2017;34(3):362-376. doi: 10.14573/altex.1609122.
  • Amin ND, Paşca SP. Building Models of Brain Disorders with Three-Dimensional Organoids. Neuron. 2018 Oct 24;100(2):389-405. doi: 10.1016/j.neuron.2018.10.007.

Glioblastoma model:

  • Plummer S, Wallace S, Ball G, Lloyd R, Schiapparelli P, Quiñones-Hinojosa A, Hartung T, Pamies D. A Human iPSC-derived 3D platform using primary brain cancer  cells to study drug development and personalized medicine. Sci Rep. 2019 Feb 5;9(1):1407. doi: 10.1038/s41598-018-38130-0.

Organoids vascularization:

  • Grebenyuk S, Ranga A. Engineering Organoid Vascularization. Front Bioeng Biotechnol. 2019 Mar 19;7:39. doi: 10.3389/fbioe.2019.00039.
  • Pham MT, Pollock KM, Rose MD, Cary WA, Stewart HR, Zhou P, Nolta JA, Waldau B. Generation of human vascularized brain organoids. Neuroreport. 2018 May 2;29(7):588-593. doi: 10.1097/WNR.0000000000001014.

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