Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles

Bruna Corradetti; Paz Freile; Steve Pells; Pierre Bagnaninchi; Jason Park; Tarek M. Fahmy; Paul A. de Sousa

doi:10.1016/j.biomaterials.2012.06.011

Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles

Bruna Corradetti, Paz Freile, Steve Pells, Pierre Bagnaninchi, Jason Park, Tarek M. Fahmy, Paul A. de Sousa

Houston Methodist

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Stem cell growth and differentiation is controlled by intrinsic and extrinsic factors. The latter includes growth factors, which are conventionally supplied in vitro in media exchanged daily. Here, we illustrate the use of affinity targeted biodegradable nanoparticles to mediate paracrine stimulation as an alternative approach to sustain the growth and pluripotency of mouse embryonic stem cells. Leukaemia Inhibitory Factor (LIF) was encapsulated in biodegradable nanoparticles and targeted to the cell surface using an antibody to the oligosaccharide antigen SSEA-1. Sustained release of LIF from nanoparticles composed of a solid Poly(lactide-co-glycolic acid) polyester or a hydrogel-based liposomal system, we term Nanolipogel, replenished once after each cell passage, proved as effective as daily replenishment with soluble LIF for maintenance of pluripotency after 5 passages using 10⁴-fold less LIF. Our study constitutes an alternative paradigm for stem cell culture, providing dynamic microenvironmental control of extrinsic bioactive factors benefiting stem cell manufacturing.

Original language	English (US)
Pages (from-to)	6634-6643
Number of pages	10
Journal	Biomaterials
Volume	33
Issue number	28
DOIs	https://doi.org/10.1016/j.biomaterials.2012.06.011
State	Published - Oct 2012

Keywords

Biodegradable nanoparticles
Embryonic stem cell
Paracrine delivery
Renewal

ASJC Scopus subject areas

Bioengineering
Ceramics and Composites
Biophysics
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2012.06.011

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title = "Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles",

abstract = "Stem cell growth and differentiation is controlled by intrinsic and extrinsic factors. The latter includes growth factors, which are conventionally supplied in vitro in media exchanged daily. Here, we illustrate the use of affinity targeted biodegradable nanoparticles to mediate paracrine stimulation as an alternative approach to sustain the growth and pluripotency of mouse embryonic stem cells. Leukaemia Inhibitory Factor (LIF) was encapsulated in biodegradable nanoparticles and targeted to the cell surface using an antibody to the oligosaccharide antigen SSEA-1. Sustained release of LIF from nanoparticles composed of a solid Poly(lactide-co-glycolic acid) polyester or a hydrogel-based liposomal system, we term Nanolipogel, replenished once after each cell passage, proved as effective as daily replenishment with soluble LIF for maintenance of pluripotency after 5 passages using 104-fold less LIF. Our study constitutes an alternative paradigm for stem cell culture, providing dynamic microenvironmental control of extrinsic bioactive factors benefiting stem cell manufacturing.",

keywords = "Biodegradable nanoparticles, Embryonic stem cell, Paracrine delivery, Renewal",

author = "Bruna Corradetti and Paz Freile and Steve Pells and Pierre Bagnaninchi and Jason Park and Fahmy, {Tarek M.} and {de Sousa}, {Paul A.}",

note = "Funding Information: This work was supported by EUFP7 funding to PDS, as part of a HEALTH-2007-1.4-7 program to develop of stem cell culture conditions (Project No. 223410), and a pilot award to TMF provided by the Yale Autoimmunity Center of Excellence U19A1082713-04. Authors thank Dr Kay Samuel for assistance with FACS experiments, Eirini Koutsouraki for the advice provided for molecular analysis, Heidi K. Mjoseng for assistance with cell culture and Nina Bauer for advise on figure preparation. The authors also thank Dr. Su Metcalfe for helpful discussions at the outset of this study. ",

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AU - Park, Jason

AU - Fahmy, Tarek M.

AU - de Sousa, Paul A.

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N2 - Stem cell growth and differentiation is controlled by intrinsic and extrinsic factors. The latter includes growth factors, which are conventionally supplied in vitro in media exchanged daily. Here, we illustrate the use of affinity targeted biodegradable nanoparticles to mediate paracrine stimulation as an alternative approach to sustain the growth and pluripotency of mouse embryonic stem cells. Leukaemia Inhibitory Factor (LIF) was encapsulated in biodegradable nanoparticles and targeted to the cell surface using an antibody to the oligosaccharide antigen SSEA-1. Sustained release of LIF from nanoparticles composed of a solid Poly(lactide-co-glycolic acid) polyester or a hydrogel-based liposomal system, we term Nanolipogel, replenished once after each cell passage, proved as effective as daily replenishment with soluble LIF for maintenance of pluripotency after 5 passages using 104-fold less LIF. Our study constitutes an alternative paradigm for stem cell culture, providing dynamic microenvironmental control of extrinsic bioactive factors benefiting stem cell manufacturing.

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Paracrine signalling events in embryonic stem cell renewal mediated by affinity targeted nanoparticles

Abstract

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