Nanoplex-Mediated Codelivery of Fibroblast Growth Factor and Bone Morphogenetic Protein Genes Promotes Osteogenesis in Human Adipocyte-Derived Mesenchymal Stem Cells

Keerthi Atluri; Denise Seabold; Liu Hong; Satheesh Elangovan; Aliasger K Salem

doi:10.1021/acs.molpharmaceut.5b00297

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Nanoplex-Mediated Codelivery of Fibroblast Growth Factor and Bone Morphogenetic Protein Genes Promotes Osteogenesis in Human Adipocyte-Derived Mesenchymal Stem Cells

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Nanoplex-Mediated Codelivery of Fibroblast Growth Factor and Bone Morphogenetic Protein Genes Promotes Osteogenesis in Human Adipocyte-Derived Mesenchymal Stem Cells

Keerthi Atluri, Denise Seabold, Liu Hong, Satheesh Elangovan and Aliasger K Salem

Molecular pharmaceutics, Vol.12(8), pp.3032-3042

08/03/2015

DOI: 10.1021/acs.molpharmaceut.5b00297

PMCID: PMC4613810

PMID: 26121311

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http://doi.org/10.1021/acs.molpharmaceut.5b00297View

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Abstract

This study highlights the importance of transfection mediated coordinated bone morphogenetic protein 2 (BMP-2) and fibroblast growth factor 2 (FGF-2) signaling in promoting osteogenesis. We employed plasmids independently encoding BMP-2 and FGF-2 complexed with polyethylenimine (PEI) to transfect human adipose derived mesenchymal stem cells (hADMSCs) in vitro. The nanoplexes were characterized for size, surface charge, in vitro cytotoxicity, and transfection ability in hADMSCs. A significant enhancement in BMP-2 protein secretion was observed on day 7 post-transfection of hADMSCs with PEI nanoplexes loaded with both pFGF-2 and pBMP-2 (PEI/(pFGF-2+pBMP-2)) versus transfection with PEI nanoplexes of either pFGF-2 alone or pBMP-2 alone. Osteogenic differentiation of transfected hADMSCs was determined by measuring osteocalcin and Runx-2 gene expression using real time polymerase chain reactions. A significant increase in the expression of Runx-2 and osteocalcin was observed on day 3 and day 7 post-transfection, respectively, by cells transfected with PEI/(pFGF-2+pBMP-2) compared to cells transfected with nanoplexes containing pFGF-2 or pBMP-2 alone. Alizarin Red staining and atomic absorption spectroscopy revealed elevated levels of calcium deposition in hADMSC cultures on day 14 and day 30 post-transfection with PEI/(pFGF-2+pBMP-2) compared to other treatments. We have shown that codelivery of pFGF-2 and pBMP-2 results in a significant enhancement in osteogenic protein synthesis, osteogenic marker expression, and subsequent mineralization. This research points to a new clinically translatable strategy for achieving efficient bone regeneration.

Bone Regeneration - physiology

Genetic Therapy

Fibroblast Growth Factor 2 - chemistry

Humans

Adipocytes - cytology

Bone Morphogenetic Protein 2 - chemistry

Cell Differentiation - genetics

Mesenchymal Stromal Cells - cytology

Transfection

Bone Morphogenetic Protein 2 - metabolism

Polyethyleneimine - chemistry

Plasmids - genetics

Fibroblast Growth Factor 2 - metabolism

Osteogenesis - genetics

Bone Morphogenetic Protein 2 - genetics

Tissue Engineering - methods

DNA - pharmacology

Cells, Cultured

Mesenchymal Stromal Cells - metabolism

Polyethyleneimine - pharmacology

DNA - chemistry

Fibroblast Growth Factor 2 - genetics

Adipocytes - metabolism

Bone Marrow Cells - metabolism

Plasmids - administration & dosage

Details

Title: Subtitle: Nanoplex-Mediated Codelivery of Fibroblast Growth Factor and Bone Morphogenetic Protein Genes Promotes Osteogenesis in Human Adipocyte-Derived Mesenchymal Stem Cells
Creators: Keerthi Atluri - †Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, United States
Denise Seabold - ‡Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, Iowa 52242, United States
Liu Hong - ‡Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, Iowa 52242, United States
Satheesh Elangovan - ‡Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, Iowa 52242, United States
Aliasger K Salem - ‡Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, Iowa 52242, United States
Resource Type: Journal article
Publication Details: Molecular pharmaceutics, Vol.12(8), pp.3032-3042
DOI: 10.1021/acs.molpharmaceut.5b00297
PMID: 26121311
PMCID: PMC4613810
NLM abbreviation: Mol Pharm
ISSN: 1543-8392
eISSN: 1543-8392
Publisher: United States
Grant note: 1R21DE02420601A1 / NIDCR NIH HHS P30 CA086862 / NCI NIH HHS R21 DE024206 / NIDCR NIH HHS 5P30CA086862 / NCI NIH HHS
Language: English
Date published: 08/03/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Prosthodontics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Periodontics
Record Identifier: 9983985836402771

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