Xiaolin Cui1, Junnan Tang2,3, Yusak Hartanto1, Jiabin Zhang1, Jingxiu Bi1, Sheng Dai4, Shi Zhang Qiao1, Ke Cheng3, Hu Zhang1,5. 1. School of Chemical Engineering , The University of Adelaide , Adelaide 5000 , Australia. 2. Department of Cardiology , The First Affiliated Hospital of Zhengzhou University , Zhengzhou , Henan 450052 , China. 3. Joint Department of Biomedical Engineering , University of North Carolina at Chapel Hill and North Carolina State University , Raleigh , North Carolina 27695 , United States. 4. School of Chemical Engineering and Advanced Materials , Newcastle University , Newcastle upon Tyne NE1 7RU , United Kingdom. 5. Amgen Bioprocessing Centre , Keck Graduate Institute , Claremont , California 91711 , United States.
Abstract
To tune the chemical, physical, and mechanical microenvironment for cardiac stromal cells to treat acute myocardial infarction (MI), we prepared a series of thermally responsive microgels with different surface charges (positive, negative, and neutral) and different degrees of hydrophilicity, as well as functional groups (carboxyl, hydroxyl, amino, and methyl). These microgels were used as injectable hydrogels to create an optimized microenvironment for cardiac stromal cells (CSCs). Our results indicated that a hydrophilic and negatively charged microenvironment created from poly( N-isopropylacrylamide- co-itaconic acid) was favorable for maintaining high viability of CSCs, promoting CSC proliferation and facilitating the formation of CSC spheroids. A large number of growth factors, such as vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-1), and stromal-derived factor-1 (SDF-1) were released from the spheroids, promoting neonatal rat cardiomyocyte activation and survival. After injecting the poly( N-isopropylacrylamide- co-itaconic acid) microgel into mice, we examined their acute inflammation and T-cell immune reactions. The microgel itself did not elicit obvious immune response. We then injected the same microgel-encapsulated with CSCs into MI mice. The result revealed the treatment-promoted MI heart repair through angiogenesis and inhibition of apoptosis with an improved cell retention rate. This study will open a door for tailoring poly( N-isopropylacrylamide)-based microgel as a delivery vehicle for CSC therapy.
To tune the chemical, physical, and mechanical microenvironment for cardiac stromal cells to treat acute myocardial infarction (MI), we prepared a series of thermally responsive microgels with different surface charges (positive, negative, and neutral) and different degrees of hydrophilicity, as well as functional groups (n class="Chemical">carboxyl, hydroxyl, amino, and methyl). These microgels were used as injectable hydrogels to create an optimized microenvironment for cardiac stromal cells (CSCs). Our results indicated that a hydrophilic and negatively charged microenvironment created from poly( N-isopropylacrylamide- co-itaconic acid) was favorable for maintaining high viability of CSCs, promoting CSC proliferation and facilitating the formation of CSC spheroids. A large number of growth factors, such as vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-1), and stromal-derived factor-1 (SDF-1) were released from the spheroids, promoting neonatal rat cardiomyocyte activation and survival. After injecting the poly( N-isopropylacrylamide- co-itaconic acid) microgel into mice, we examined their acute inflammation and T-cell immune reactions. The microgel itself did not elicit obvious immune response. We then injected the same microgel-encapsulated with CSCs into MI mice. The result revealed the treatment-promoted MI heart repair through angiogenesis and inhibition of apoptosis with an improved cell retention rate. This study will open a door for tailoring poly( N-isopropylacrylamide)-based microgel as a delivery vehicle for CSC therapy.
Authors: Junnan Tang; Teng Su; Ke Huang; Phuong-Uyen Dinh; Zegen Wang; Adam Vandergriff; Michael T Hensley; Jhon Cores; Tyler Allen; Taosheng Li; Erin Sproul; Emily Mihalko; Leonard J Lobo; Laura Ruterbories; Alex Lynch; Ashley Brown; Thomas G Caranasos; Deliang Shen; George A Stouffer; Zhen Gu; Jinying Zhang; Ke Cheng Journal: Nat Biomed Eng Date: 2018-01-10 Impact factor: 25.671
Authors: Anh H Nguyen; Paul Marsh; Lauren Schmiess-Heine; Peter J Burke; Abraham Lee; Juhyun Lee; Hung Cao Journal: J Biol Eng Date: 2019-06-28 Impact factor: 4.355