The challenge of developing human 3D organoids into medicines

Abstract

The capacity of organoids to generate complex 3D structures resembling organs is revolutionizing the fields of developmental and stem cell biology. We are currently establishing the foundations for translational applications of organoids such as drug screening, personalized medicine and launching the future of cell therapy using organoids. However, clinical translation of organoids into cell replacement therapies is halted due to (A) a few preclinical studies demonstrating their efficacy and (B) the lack of robust, reproducible, and scalable methods of production in compliance with current pharmaceutical standards. In this issue of Stem Cell Research & Therapy [ref], Dossena and collaborators present a validated bioprocess design for large-scale production of human pancreatic organoids from cadaveric tissue in accordance with current good manufacturing practice. The authors also propose a set of specifications of starting materials and critical quality attributes of final products that are of interest to other developments provided that this type of medicines are different than any other medicinal product due to their complex composition and living nature of the active ingredient. Although large-scale production of functional cells secreting insulin is still a challenge, the development of methods such as the one presented by Dossena and collaborators contributes to move toward clinical use of organoids in the treatment of type 1 diabetes and opens avenues for future clinical use of organoids in degenerative pathologies.

Advances in Gold Nanoparticle-Based Combined Cancer Therapy

“…Spheroids, and patient derived organoids, should be seen as avascular tumors, with limitations. To move towards personalized medical care with GNPs-using organoids as an assessment tool-certain strategies will have to be employed and obstacles overcome [184]. First, many more preclinical studies will have to be undertaken involving the use of GNPs with spheroids and their ability to accurately predict tumor response.…”

Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective

“…It is practical to build complex 3D structures comprising multiple cell types as co-cultures either with established cell lines (spheroids) or PD cells (PDO) that correspond more closely to the organ or tumor tissues of interest. The PDO models [49] can show macroscopic functional responses [119,120,140] markedly different from those of the 2D counterparts and closer to the patient responses [121,133,134] due to their ability to emulate the 3D architectures and cell-cell interactions in patient's TME.…”

“…Since then, 3D cultures and organoids have been developed for a wide range of cell types [49,108,111,112,[119][120][121][122][123][124][125]. There are many types of support matrices now available, from the widely used Matrigel (a mouse sarcoma cell extracellular matrix) to other organic polymer supports such as alginates and hydrogels [126][127][128][129][130][131][132][133][134]. Three-dimensional cultures can also be induced without matrix support by concentrating "magnetized" cells via introduction of nano magnetic beads under a magnetic field [121,135].…”

3D culture models to study SARS-CoV-2 infectivity and antiviral candidates: From spheroids to bioprinting

“…Some of the challenges in culturing organoids are related to the lack of vascularization, neuronal circuit, immune system, reproducibility, and preclinical validation [ [80] , [81] , [82] ]. However, the results discussed above indicate that organoids not only are capable of recapitulate the native tissue morphology, physiology, and functionality, but also may substantially contribute to studies of SARS-CoV-2 infection mechanisms, drug screening and disease research.…”