Organoid Technologies for Research and Product Development

 
 

Functional Organoid Therapeutics 

Organoid Therapeutics has a portfolio of pending patents for organ engineering and tissue repair technologies spanning multidisciplinary fields including tissue engineering, regenerative medicine, genetic engineering, and advanced robotics for large scale manufacturing.

 
 
 
 
 
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Organoids

While the demand for organs continues to increase, the number of organs available for transplantation remains problematically low. Organoid-based technologies are a promising alternative solution to this problem and offer significant advantages over the traditional approach.

Organoid Therapeutics' biopharmaceutical products offer patients with end-stage glandular organ disease an alternative to a lifetime of pharmacological therapy. Our functional glandular organs are made using human organoid-based technologies, genetic engineering, next-gen biomaterials, transplantation science, and advanced robotics for large scale manufacturing.

 
 
 

Induced Pluripotent Stem Cells

iPSCs are derived from skin or blood cells that have been reprogrammed back into an embryonic-like state from which the cells can be grown into any type of human cell needed for therapeutic purposes. At Organoid Therapeutics, we aim to use iPSCs to generate the insulin-producing pancreatic islet cells that will be incorporated in our pancreatic organoids. Additionally, our technology is a self-regulating palliative that will not require immunosuppressants to ward off the body’s immune reaction. The genetically modified iPSC’s will be universally compatible to prevent immunorejection.

 
 
 

Biologic Scaffolds

Unlike synthetic biomaterials, Organoid Therapeutics’ first-of-its-kind proprietary substrate derived from pancreatic extracellular matrix (ECM) has immunomodulatory properties that prevent inflammation and adverse reactions. Additionally, the pancreatic ECM is the most familiar and natural microenvironment for pancreatic cells, ideal for promoting homeostasis and adequate function.

 
 
 
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Genetic Engineering

The concept of cell transplantation is not novel. However, a recurring and unresolved problem associated with this approach is immunorejection. Various strategies have been proposed to prevent immunorejection including using each patient’s own cells and the establishment of HLA-typed cell banks. However, these approaches have been proven to be resource intensive making scaling up unrealistic. In contrast, Organoid Therapeutics’ approach consists of using CRISPR-Cas9 modification of HLA molecules to establish universally compatible cell banks of ready-to-use organoids.

 
 
 
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Functional Vascular Network

Native pancreatic islet cells contain a dense capillary network to deliver nutrients and oxygen to the cells while carrying away cellular products and waste. However, all current initiatives to regenerative pancreatic islet transplantation attempt to generate a homogenous endocrine population without vasculature. Without vascularization, these therapies cannot be translated to clinical applications as the cells will die within a few days. Our technology is unique in that it encourages the formation of microvasculature within the organoids by integrating micro-vessel fragments in the 3D coculture, leading to the formation of a functional vascular network that can be integrated seamlessly into the host vasculature post-implantation.

 
 
 
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Advanced Robotics for Manufacturing

The number of stem cells that would need to be cultured for mass-production of organoids on a commercial scale cannot be achieved using standard cell culture procedures. As it stands now, cultivating stem cells is a highly involved process and would be far too costly in terms of personnel and time. Organoid Therapeutics aims to drastically reduce these costs via robotic automation of cell culture tasks. We aim to use machine learning and advanced robotics to create a modular system that streamlines the manufacturing process and allows for procedures to be adjusted in order to adjust manufacturing conditions to match the needs of the type of organoid being made.

 
 
 
 
 

Competitive Advantage 

Advantages Over Current Treatment Options: 

  • Organoids are self-regulating. 

  • No risk of dosage regimen-related complications. 

  • Non-compliance is not possible after organoid injection, but frequent with insulin injections. 

  • Trained personnel (healthcare providers or patients themselves) are required for adequate, recurrent insulin administration, but only once for organoid injection. 

  • Currently available autonomous technologies such as insulin pumps are malfunction-prone and expensive, and still require a continuous supply of consumable products to operate. 

Advantages Over Novel Treatments in Development: 

  • Universally immunocompatible approach. 

  • Mitigation of foreign body reaction/encapsulation. 

  • Vascularization of implanted constructs. 

  • Cell and biological scaffold material sourcing 

 
 
 

Awards and Accomplishments

  • Awarded a $225,000 DARPA STTR Phase I which was successful in the identification and validation of genetically engineered immuno-compatible pancreatic organoids. 

  • Our group has shown functional human pancreatic organoids with a living vascular network capable of rescuing a mouse model of diabetes and modulating the immune response away from chronic pro-inflammatory towards long term acceptance. 

  • Closed $1.5M pre-seed convertible note round from friends and family. 

  • 2019 Tech-Connect World Innovation Award: Selected among the top 15% tech companies from global academic technology transfer offices, SBIR/STTR awardees, and early-stage companies.   

  • 2019 Defense TechConnect Innovation Award: Recognized within the top 15% of submitted technologies as ranked by the Selection Committee. Rankings are based on the potential positive impact the submitted technology will have for the warfighter and national security.  

  • Working with the National Institutes of Health (NIDDK) to conduct a $1.7M preclinical studies of product safety and efficacy optimization.  

  • Accepted into Carnegie Mellon’s Swartz Center for Entrepreneurship Startup Incubator. 

 
 
 

  • Londono, R. & Badylak, S. F. Biologic Scaffolds for Regenerative Medicine: Mechanisms of In vivo Remodeling. Ann. Biomed. Eng. 43, 577–592 (2015).

  • Londono, R. et al. The effect of cell debris within biologic scaffolds upon the macrophage response. J. Biomed. Mater. Res. - Part A 105, (2017).

  • Faulk, D. M. et al. ECM hydrogel coating mitigates the chronic inflammatory response to polypropylene mesh. Biomaterials 35, (2014).

  • Loneker, A. E., Faulk, D. M., Hussey, G. S., D’Amore, A. & Badylak, S. F. Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype in-vitro. J. Biomed. Mater. Res. - Part A (2016). doi:10.1002/jbm.a.35636

  • Candiello, J., Singh, S. S., Task, K., Kumta, P. N. & Banerjee, I. Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness. J. Biol. Eng. (2013). doi:10.1186/1754-1611-7-9

  • Lienert, F., Lohmueller, J. J., Garg, A. & Silver, P. A. Synthetic biology in mammalian cells: Next generation research tools and therapeutics. Nature Reviews Molecular Cell Biology (2014). doi:10.1038/nrm3738

Publications