Local delivery of stem cell growth factors with injectable hydrogels for myocardial therapy

Event Abstract Back to Event Local delivery of stem cell growth factors with injectable hydrogels for myocardial therapy Renae Waters1, 2, Settimio Pacelli1, Ryan Maloney1, 2 and Arghya Paul1, 2 1 University of Kansas, Chemical and Petroleum Engineering, United States 2 School of Engineering, University of Kansas, Bioengineering Graduate Program, United States Introduction: Stem cell therapy offers a promising approach to regenerate damaged cardiac tissue after acute myocardial infarction. Recent evidences have attributed such improvement to the broad repertoire of angiogenic paracrine factors (growth factors, chemokines and exosomes) secreted by the stem cells, known as secretome[1]. Here, we intend (i) to efficiently bio-manufacture cell secretome from 3D stem cell aggregates using a microfluidic system and (ii) efficiently deliver the harnessed secretome for cardiac repair and revascularization applications using a hydrogel-based injectable delivery system. Experiments and Results: As a first step, a microfluidic device consisting of deep concave microwell arrays was fabricated using soft lithography microscale techniques. Results demonstrate that bone marrow derived human mesenchymal stem cell (hMSC) suspensions, injected to the microfluidic chip through inlet port, form uniformly sized aggregates (~220μm diameter) within 2 days. Computational analysis confirmed rapid oxygen diffusion in the microwells. 3 days post-incubation, hMSC secretome (4.5-9 times increase in angiogenic protein concentrations compared to 2D culture including VEGF, FGF, Angiogenin) was collected, leaving behind the hMSC aggregates at the bottom of the well. As a next step, a physically cross-linked injectable nanocomposite hydrogel, comprising of silicate nanoplatelets and gelatin, was formulated to deliver the harnessed hMSC secretome to the target site. In vitro studies confirmed controlled release of bioactive hMSC growth factors from the hydrogel which induced proliferation of human endothelial cells (HUVEC). For in vivo studies rat model with acute myocardial infarction (n=5) was used. The secretome carrying hydrogel was injected intramyocardially at the per-infarct region of the heart, post infarction as mentioned in earlier work[2]. After 3 weeks, the animals were sacrificed and the injected tissue regions were examined for histological analysis. Masson’s Trichome staining confirmed reduced scar area in the treated Secretome+ group (3D cell aggregates) compared to control group (secretome from 2D cell culture). Immunostaining with CD31 antibodies also confirmed significantly high local myocardial angiogenesis at the injected site in Secretome+ group. These data confirms the angiogenic therapeutic potential of the developed hydrogel in vitro and in vivo. Conclusion: Take together, this study reports a novel strategy to utilize cell secretome, as an alternate to traditional cell therapy, for myocardial regeneration therapy. The strategy can also be used for other biomedical applications, such as wound healing and vascular tissue engineering. Arghya Paul likes to acknowledge the Institutional Development Award (IDeA) from the National Institute of General Medical Sciences, National Institutes of Health (NIH), under Award Number P20GM103638.References:[1] Burdon TJ, Paul A, Noiseux N, Prakash S, Shum-Tim D (2011). Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential. Bone Marrow Res. 2011:207326.[2] Paul A et al (2014). Injectable graphene oxide/hydrogel-based angiogenic gene delivery system for vasculogenesis and cardiac repair. ACS Nano; 8(8):8050-62. Keywords: Hydrogel, stem cell, growth factor, Bioactivity Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Biomimetic materials Citation: Waters R, Pacelli S, Maloney R and Paul A (2016). Local delivery of stem cell growth factors with injectable hydrogels for myocardial therapy. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00063 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul Google Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul Google Scholar Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul PubMed Renae Waters Settimio Pacelli Ryan Maloney Arghya Paul Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.