Journal article
Cellular and extracellular programming of cell fate through engineered intracrine-, paracrine-, and endocrine-like mechanisms
Biomaterials, Vol.32(11), pp.3053-3061
04/2011
DOI: 10.1016/j.biomaterials.2010.12.036
PMCID: PMC3043463
PMID: 21262537
Abstract
A cell’s fate is tightly controlled by its microenvironment. Key factors contributing to this microenvironment include physical contacts with the extracellular matrix and neighboring cells, in addition to soluble factors produced locally or distally. Alterations to these cues can drive homeostatic processes, such as tissue regeneration/wound healing, or may lead to pathologic tissue dysfunction. In vitro models of cell and tissue microenvironments are desirable for enhanced understanding of the biology and ultimately for improved treatment. However, mechanisms to exert specific control over cellular microenvironments remains a significant challenge. Genetic modification has been used but is limited to products that can be manufactured by cells and release kinetics of therapeutics cannot easily be controlled. Herein we describe a non-genetic approach to engineer cells with an intracellular depot of phenotype altering agent/s that can be used for altering cell fate via intracrine-, paracrine-, and endocrine-like mechanisms. Specifically, we show that human mesenchymal stem cells (MSCs) can be engineered with poly lactide-co-glycolic acid (PLGA) particles containing dexamethasone, which acts on cytoplasmic receptors. The controlled release properties of these particles allowed for sustained intracellular and extracellular delivery of agent to promote differentiation of particle-carrying cells, as well as neighboring cells and distant cells that do not contain particles.
Details
- Title: Subtitle
- Cellular and extracellular programming of cell fate through engineered intracrine-, paracrine-, and endocrine-like mechanisms
- Creators
- Debanjan Sarkar - Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USAJames A Ankrum - Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USAGrace S.L Teo - Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USAChristopher V Carman - Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAJeffrey M Karp - Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
- Resource Type
- Journal article
- Publication Details
- Biomaterials, Vol.32(11), pp.3053-3061
- DOI
- 10.1016/j.biomaterials.2010.12.036
- PMID
- 21262537
- PMCID
- PMC3043463
- NLM abbreviation
- Biomaterials
- ISSN
- 0142-9612
- eISSN
- 1878-5905
- Publisher
- Elsevier Ltd
- Grant note
- name: National Institute of Health, award: HL097172, HL095722, DE019191; DOI: 10.13039/100000968, name: American Heart Association, award: 0970178N
- Language
- English
- Date published
- 04/2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering
- Record Identifier
- 9984000931202771
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