Effects of drugs can be tested realistically, without experimentation on animals.
Micro-organ devices (MODs) are being developed to satisfy an emerging need for small, lightweight, reproducible, biological-experimentation apparatuses that are amenable to automated operation and that impose minimal demands for resources (principally, power and fluids). MODs are intended to overcome major disadvantages of conventional in vitro and conventional in vivo experimentation for purposes of investigating effects of medicines, toxins, and possibly other foreign substances.
Conventional in vitro cell cultures do not mimic the complex environments to which toxins and medicines are subjected in living organisms. Conventional in vivo studies in non-human animals can account for complex intercellular and intertissue effects not observable in in vitro tests, but experimentation on animals is expensive, labor intensive, time-consuming, and unpopular. Moreover, cross-species extrapolation of toxicity and pharmacokinetic characteristics is problematic. In contrast, because MODs could host life-like miniature assemblies of human cells, the effects observed in tests performed in MODs could be extrapolated more readily to humans than could effects observed in conventional in vitro cell cultures, making it possible to reduce or eliminate experimentation on animals.
In simplest terms, a MOD is a microfluidic device containing a variety of microstructures and assemblies of cells (see figure), all designed to mimic a complex in vivo microenvironment by replicating one or more in vivo micro- organ structures, the architectures and composition of the extracellular matrices in the organs of interest, and the in vivo fluid flows. In addition to microscopic flow channels, a MOD contains one or more micro-organ wells containing cells residing in microscopic extracellular matrices and/or scaffolds, the shapes and compositions of which enable replication of the corresponding in vivo cell assemblies and flows.
Once the basic microfluidic device infrastructure of a MOD containing micro-organ wells and flow channels has been fabricated, single cells or multiple cells of the same type or different types needed for a given micro- organ are encapsulated or suspended in a solution that may contain micro-organ-specific extracellular matrix molecules and scaffolding. The suspension or solution is placed in a syringe that is part of a computer-controlled apparatus; under computer control, cells and any extracellular matrix material are dispensed as the syringe is moved, thereby effectively printing a unitary three-dimensional assembly of cells and extracellular matrix material into a micro-organ well. The dimensions of each printed micro-organ are chosen so as not to exceed optimum dimensions for perfusion of cells with nutrient fluid, exchange of gases between the cells and the nutrient fluid, and removal of non-gaseous cell wastes in the nutrient flow.
This work was done by Steven R. Gonda and Julia Leslie of Johnson Space Center; Robert C. Chang, Binil Starly, and Wei Sun of Drexel University; Christopher Culbertson of Kansas State University; and Heidi Holtorf of USRA. For further information, contact the JSC Innovation Partnerships Office at (281) 483-3809.
This invention is owned by NASA, and a patent application has been filed. Inquiries concerning nonexclusive or exclusive license for its commercial development should be addressed to the Patent Counsel, Johnson Space Center, (281) 483-1003. Refer to MSC-23988-1.