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Biomimetic Polymers for Cardiac Tissue Engineering.

Peña B, Martinelli V, Jeong M, Bosi S, Lapasin R, Taylor MR, Long CS, Shandas R, Park D, Mestroni L - Biomacromolecules (2016)

Bottom Line: We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia.Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days.These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.

ABSTRACT
Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

No MeSH data available.


Related in: MedlinePlus

Live/dead (green/red)staining of NRVM after 8, 14, and 21 daysof culture in different conditions: Top-row panels, 2D tissue cultureplate coated with gelatin (control). Middle-row panels, NRVM culturedin 3D PSHU-PNIPAAm-lysine. Bottom-row panels: NRMV cultured in 3DPSHU-PNIPAAm. Compared to control groups, NRVM cultured in both 3Dmatrices showed a well-developed cell-interconnected network thatmay allow better impulse propagation between cells. Scale bar: 400μm.
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fig3: Live/dead (green/red)staining of NRVM after 8, 14, and 21 daysof culture in different conditions: Top-row panels, 2D tissue cultureplate coated with gelatin (control). Middle-row panels, NRVM culturedin 3D PSHU-PNIPAAm-lysine. Bottom-row panels: NRMV cultured in 3DPSHU-PNIPAAm. Compared to control groups, NRVM cultured in both 3Dmatrices showed a well-developed cell-interconnected network thatmay allow better impulse propagation between cells. Scale bar: 400μm.

Mentions: The effect of the 3D PSHU-PNIPAAm systemson the viability of NRVMs was first assessed using live/dead staining.Cells were analyzed in complete medium at different time points during3 weeks. Traditional 2D gelatin coating culture dishes, prepared aspreviously described, were used as controls.4,44,45Figure 3 shows the live/dead results.


Biomimetic Polymers for Cardiac Tissue Engineering.

Peña B, Martinelli V, Jeong M, Bosi S, Lapasin R, Taylor MR, Long CS, Shandas R, Park D, Mestroni L - Biomacromolecules (2016)

Live/dead (green/red)staining of NRVM after 8, 14, and 21 daysof culture in different conditions: Top-row panels, 2D tissue cultureplate coated with gelatin (control). Middle-row panels, NRVM culturedin 3D PSHU-PNIPAAm-lysine. Bottom-row panels: NRMV cultured in 3DPSHU-PNIPAAm. Compared to control groups, NRVM cultured in both 3Dmatrices showed a well-developed cell-interconnected network thatmay allow better impulse propagation between cells. Scale bar: 400μm.
© Copyright Policy - editor-choice
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4863197&req=5

fig3: Live/dead (green/red)staining of NRVM after 8, 14, and 21 daysof culture in different conditions: Top-row panels, 2D tissue cultureplate coated with gelatin (control). Middle-row panels, NRVM culturedin 3D PSHU-PNIPAAm-lysine. Bottom-row panels: NRMV cultured in 3DPSHU-PNIPAAm. Compared to control groups, NRVM cultured in both 3Dmatrices showed a well-developed cell-interconnected network thatmay allow better impulse propagation between cells. Scale bar: 400μm.
Mentions: The effect of the 3D PSHU-PNIPAAm systemson the viability of NRVMs was first assessed using live/dead staining.Cells were analyzed in complete medium at different time points during3 weeks. Traditional 2D gelatin coating culture dishes, prepared aspreviously described, were used as controls.4,44,45Figure 3 shows the live/dead results.

Bottom Line: We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia.Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days.These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Institute and ‡Bioengineering Department, University of Colorado-Denver , Aurora, Colorado, United States.

ABSTRACT
Heart failure is a morbid disorder characterized by progressive cardiomyocyte (CM) dysfunction and death. Interest in cell-based therapies is growing, but sustainability of injected CMs remains a challenge. To mitigate this, we developed an injectable biomimetic Reverse Thermal Gel (RTG) specifically engineered to support long-term CM survival. This RTG biopolymer provided a solution-based delivery vehicle of CMs, which transitioned to a gel-based matrix shortly after reaching body temperature. In this study we tested the suitability of this biopolymer to sustain CM viability. The RTG was biomolecule-functionalized with poly-l-lysine or laminin. Neonatal rat ventricular myocytes (NRVM) and adult rat ventricular myocytes (ARVM) were cultured in plain-RTG and biomolecule-functionalized-RTG both under 3-dimensional (3D) conditions. Traditional 2D biomolecule-coated dishes were used as controls. We found that the RTG-lysine stimulated NRVM to spread and form heart-like functional syncytia. Regarding cell contraction, in both RTG and RTG-lysine, beating cells were recorded after 21 days. Additionally, more than 50% (p value < 0.05; n = 5) viable ARVMs, characterized by a well-defined cardiac phenotype represented by sarcomeric cross-striations, were found in the RTG-laminin after 8 days. These results exhibit the tremendous potential of a minimally invasive CM transplantation through our designed RTG-cell therapy platform.

No MeSH data available.


Related in: MedlinePlus