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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

Fluorescence sarcomeric α-actinin (green)and DAPI (blue)staining of ARVM in different conditions: (A) 2D tissue culture platecoated with laminin (control), (B) 3D PSHU-PNIPAAm-laminin, and (C)3D PSHU-PNIPAAm. Top-row panels ARVM after 3 days of culture. Bottom-rowpanels ARVM after 8 days of culture. Compared to control groups wefound that the 3D PSHU-PNIPAAm-laminin matrix allows a long-term ARVMsurvival with a well-defined cardiac phenotype represented by a sarcomerestriation.
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fig8: Fluorescence sarcomeric α-actinin (green)and DAPI (blue)staining of ARVM in different conditions: (A) 2D tissue culture platecoated with laminin (control), (B) 3D PSHU-PNIPAAm-laminin, and (C)3D PSHU-PNIPAAm. Top-row panels ARVM after 3 days of culture. Bottom-rowpanels ARVM after 8 days of culture. Compared to control groups wefound that the 3D PSHU-PNIPAAm-laminin matrix allows a long-term ARVMsurvival with a well-defined cardiac phenotype represented by a sarcomerestriation.

Mentions: Figure 8 shows theα-sarcomeric actinin and DAPI immunofluorescence staining ofARVM after 3 and 8 days of culture. After 3 days of culture, all thesamples showed a well-defined cardiac phenotype represented by a sarcomerestriation. Similar results were observed in the remaining cells after8 days of culture. Compared with control groups, PSHU-PNIPAAm-lamininshowed promising capability to support ARVM survival while also preservingtheir cardiac phenotype.


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)

Fluorescence sarcomeric α-actinin (green)and DAPI (blue)staining of ARVM in different conditions: (A) 2D tissue culture platecoated with laminin (control), (B) 3D PSHU-PNIPAAm-laminin, and (C)3D PSHU-PNIPAAm. Top-row panels ARVM after 3 days of culture. Bottom-rowpanels ARVM after 8 days of culture. Compared to control groups wefound that the 3D PSHU-PNIPAAm-laminin matrix allows a long-term ARVMsurvival with a well-defined cardiac phenotype represented by a sarcomerestriation.
© Copyright Policy - editor-choice
Related In: Results  -  Collection

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

fig8: Fluorescence sarcomeric α-actinin (green)and DAPI (blue)staining of ARVM in different conditions: (A) 2D tissue culture platecoated with laminin (control), (B) 3D PSHU-PNIPAAm-laminin, and (C)3D PSHU-PNIPAAm. Top-row panels ARVM after 3 days of culture. Bottom-rowpanels ARVM after 8 days of culture. Compared to control groups wefound that the 3D PSHU-PNIPAAm-laminin matrix allows a long-term ARVMsurvival with a well-defined cardiac phenotype represented by a sarcomerestriation.
Mentions: Figure 8 shows theα-sarcomeric actinin and DAPI immunofluorescence staining ofARVM after 3 and 8 days of culture. After 3 days of culture, all thesamples showed a well-defined cardiac phenotype represented by a sarcomerestriation. Similar results were observed in the remaining cells after8 days of culture. Compared with control groups, PSHU-PNIPAAm-lamininshowed promising capability to support ARVM survival while also preservingtheir cardiac phenotype.

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