Transplantation of brain cells assembled around a programmable synthetic microenvironment

Nature Biotechnology volume 19, pages934–939(2001)Cite this article

Abstract

Cell therapy is a promising method for treatment of hematopoietic disorders, neurodegenerative diseases, diabetes, and tissue loss due to trauma. Some of the major barriers to cell therapy have been partially addressed, including identification of cell populations, in vitro cell proliferation, and strategies for immunosuppression. An unsolved problem is recapitulation of the unique combinations of matrix, growth factor, and cell adhesion cues that distinguish each stem cell microenvironment, and that are critically important for control of progenitor cell differentiation and histogenesis. Here we describe an approach in which cells, synthetic matrix elements, and controlled-release technology are assembled and programmed, before transplantation, to mimic the chemical and physical microenvironment of developing tissue. We demonstrate this approach in animals using a transplantation system that allows control of fetal brain cell survival and differentiation by pre-assembly of neo-tissues containing cells and nerve growth factor (NGF)-releasing synthetic particles.

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Figure 1: Formation of neo-tissues.
Figure 2: Microparticle and synthetic microenvironment characterization.
Figure 3: NGF-enriched synthetic microenvironment-induced biological activity.
Figure 4: Predicted distribution of NGF in neo-tissues containing NGF-releasing microparticles.

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Acknowledgements

This work was supported by National Aeronautics and Space Administration (NASA) Grant NAG 8-1372 and National Institutes of Health Grant NS-038470. M.J.M. was supported by a grant from the NASA Graduate Student Research Program.

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  1. School of Chemical Engineering, Cornell University, Ithaca, 14853, NY

    Melissa J. Mahoney & W. Mark Saltzman

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  1. Melissa J. Mahoney
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  2. W. Mark Saltzman
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Correspondence to W. Mark Saltzman.

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Mahoney, M., Saltzman, W. Transplantation of brain cells assembled around a programmable synthetic microenvironment. Nat Biotechnol 19, 934–939 (2001). https://doi.org/10.1038/nbt1001-934

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