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Posted: Sep 26, 2012

Researchers developed a new technique for controlling spatial distribution of various cell types in defined 3D microenvironments

(Nanowerk News) Living systems are made of complex architectural organization of various cell types in defined microenvironments. The intricate interactions between different cell types control the specific functions of the associated tissues, such as the functions of native liver and cardiac tissues, metastasis and invasion of tumors, and embryonic development. Replicating these complex associations could be useful for fabricating 1) healthy tissues for regenerative medicine, 2) diseased tissues, such as tumors, for drug discovery, 3) models to study embryonic development, and 4) models to study tissue morphogenesis. However, it has remained a challenge to control the targeted spatial organization of multiple cell types in defined microenvironments by using previous methods.
MIT researchers have developed a new versatile technique to control spatial distribution of multiple cell types in predefined 3D geometries which was described in a paper published online September 3 in Advanced Materials ("Controlling Spatial Organization of Multiple Cell Types in Defined 3D Geometries"). They fabricated dynamic microstructures from a thermoresponsive polymer. These microstructures responded to temperature by changing their shape. MIT researchers exploited the temperature dependent shape changing characteristic of dynamic microstructures to seed different cell types at different temperatures. Spatial organization of multiple cell types was obtained in square and circular geometries.
spatial organizations of multiple cell types
A simple method to control spatial organizations of multiple cell types in predefined geometries by using poly(N-isopropylacrylamide)-based dynamic microwells is described. Dynamic microwells are used to pattern two different cell types in a spatially controlled manner by exploiting their shape changing properties at two different temperatures. Both spatial organization of two different cell types and control of pattern geometry are achieved with circular and square dynamic microwells. (©Wiley-Verlag GmbH)
Halil Tekin, the leading author of the paper, is a graduate student in electrical engineering and computer science department at MIT. Also, MIT undergraduate students, Jefferson Sanchez (MITí13), Christian Landeros (MITí14) and Karen Dubbin (MITí12) are other authors of the paper. Senior authors of the paper are Ali Khademhosseini, associate professors in the Harvard-MIT Health Sciences and Technology, and Robert Langer, the David H. Koch Institute professor at MIT. Also, other MIT undergraduate students Tonia Tsinman (MITí13) and Brianna Jones (MITí14) have contributed to the research during the early development of dynamic microstructures.
Different geometries can be obtained by using molds with different shapes. One could use these dynamic microstructures to replicate a microscale lobule of a human liver or microscale human cardiac tissues by using the associated cell types. These biomimetic tissues could be highly useful to test drug candidates without requiring the animal experiments which take more time and investment. Tissues mimicking the native tissues could also be implanted to human body.
Another application could be to recapitulate the tumor microenvironments. Various cell types associated with particular tumors could be spatially organized by using dynamic microstructures. The tumor models mimicking the native ones can be highly beneficial for drug discovery. The intricate interactions between various cell types regulating cell-signaling circuitry in a tumor microenvironment can be investigated by employing the dynamic microstructures.
MIT researchers also propose that these dynamic microstructures may potentially be useful to study embryonic development. Previous methods lacked mimicking dynamically changing geometry of embryo and controlling the spatial distribution of various cell types. The underlying mechanisms of early developmental stages could be studied by patterning associated cell types in various geometries. In the future, it would also be possible to fabricate microstructures changing their shapes by sensing the secreted proteins from the cells, which could be employed to replicate the embryonic development.
In summary, dynamic microstructures and the presented versatile technique may potentially be useful for a wide range of applications in tissue engineering, developmental biology, cancer biology, and drug discovery.
Source: By Halil Tekin, MIT
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