Heart Repair Using Nanogel-Encapsulated Human Cardiac Stem Cells in Mice and Pigs with Myocardial Infarction

Abstract

Stem cell transplantation is currently implemented clinically but is limited by low retention and engraftment of transplanted cells and the adverse effects of inflammation and immunoreaction when allogeneic or xenogeneic cells are used. Here, we demonstrate the safety and efficacy of encapsulating human cardiac stem cells (hCSCs) in thermosensitive poly(N-isopropylacrylamine-co-acrylic acid) or P(NIPAM-AA) nanogel in mouse and pig models of myocardial infarction (MI). Unlike xenogeneic hCSCs injected in saline, injection of nanogel-encapsulated hCSCs does not elicit systemic inflammation or local T cell infiltrations in immunocompetent mice. In mice and pigs with acute MI, injection of encapsulated hCSCs preserves cardiac function and reduces scar sizes, whereas injection of hCSCs in saline has an adverse effect on heart healing. In conclusion, thermosensitive nanogels can be used as a stem cell carrier: the porous and convoluted inner structure allows nutrient, oxygen, and secretion diffusion but can prevent the stem cells from being attacked by immune cells.

Ion Therapy: A Novel Strategy for Acute Myocardial Infarction

“…[16] Previous tissue engineering therapies for AMI treatment has acquired certain effect but [17][18][19][20][21][22] few observed robust myocardial regeneration and focused on the paracrine effects of angiogenesis and antiapoptosis effects stimulated by stem cells. [16] Previous tissue engineering therapies for AMI treatment has acquired certain effect but [17][18][19][20][21][22] few observed robust myocardial regeneration and focused on the paracrine effects of angiogenesis and antiapoptosis effects stimulated by stem cells.…”

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

“…Dynamic light scattering was employed to determine the size of the nanogel dispersions in phosphate‐buffered saline (PBS) at 4, 25, and 37 °C, respectively. The hydrodynamic diameters of nanogels dramatically increased from 4 to 25 °C and decreased from 25 to 37 °C, which related to the volume phase transition temperature (VPTT) of the nanogels with ≈27 °C (Figure D) . The sol–gel phase change of the nanogels was also observed, which was a solution at room temperature but changed into a soft gel at 37 °C as shown in Figure E.…”

“…Fourier transform infrared (FTIR) spectroscopy analysis was used to identify the functional groups of the nanogel. The spectrum of the nanogels exhibited main peaks at 1645 and 1540 cm −1 , which represented the chemical bond for amide I and amide II of NIPAM, respectively . The band around 1713 cm −1 was assigned to the carbonyl group of HEMA, which indicated that the poly(NIPAM‐HEMA) nanogels successfully formed (Figure S1, Supporting Information).…”

Facile Nanolization Strategy for TherapeuticGanoderma Lucidum Spore Oilto Achieve Enhanced Protection against Radiation‐Induced Heart Disease

“…Cardiac Function Measurements : At expected time intervals after exposure to X‐ray IR, mice were anesthetized by 3.0% isoflurane (RWD Life Science, China) by a breathing anesthesia machine (Matrx, USA), and were placed on the operating table in a supine position, assisting with 2% isoflurane for continuous anesthesia during detection. Cardiac function was detected by the ultrasonic equipment (VISUALISONICS, Vevo 2100 Imaging System, Canada) with an MS‐550D probe . The electrocardiogram was connected to the mice's left forelimb palm, and the left ventricular motion was recorded by M‐mode.…”