Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy

Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy

Bibliographic Details
Main Author: Li, Zhenqing
Language:English
Published: The Ohio State University / OhioLINK 2012
Subjects:
Materials Science
Myocardial Infarction
Injectable Hydrogel
Stem Cells
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1337223886
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu13372238862021-08-03T06:05:02Z Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy Li, Zhenqing Materials Science Myocardial Infarction Injectable Hydrogel Stem Cells Myocardial infarction is caused by blockage of coronary artery. The depletion of nutrient and oxygen supply immediately damages cardiomyocytes, leading to the loss of heart function. The following remodeling results in the formation of fibrous scar tissue at the infarcted site. The stiff and non-contractile scar tissue cannot restore the lost heart function. As a result, left ventricle (LV) dilation was gradually developed which causes thinning of heart wall. It further impairs the heart function, leading to a congestive heart failure.The key to the success therapy for myocardial infarction contains: 1) re-establishing the blood flow to the infarcted area; and 2) regenerating new cardiomyocytes to restore the lost heart functions. Current therapy for MI includes coronary artery by-pass grafting (CABG) or percutaneous coronary intervention (PCI), which focus more on point 1 and cannot have the lost muscle regenerated.Stem cell therapy has been proposed as a promising approach to the future of myocardial infarction therapy. The delivered stem cell is capable to differentiate into new cardiomyocytes to regenerate the damaged heart muscle. However, direct delivery of stem cells into myocardium suffers from low cell differentiation due to the mismatched environment after formation of the scar tissue. The fist half of this dissertation mainly focus on the design of an optimal hydrogel micro-environment to promote stem cell cardiac differentiation. Three families of hydrogels are developed with well controlled matrix moduli and water contents. The differentiation of mesenchymal stem cells (MSCs) and cardiosphere derived cells (CDCs) in those hydrogel matrix was investigated. It was found hydrogel of 40 kPa modulus with 40% water content is optimal for stem cell cardiac differentiation in vitro and in vivo. Furthermore, injection of 40 kPa hydrogel in vivo by a mouse MI model showed it attenuated LV dilation, improved heart function and reduced heart muscle damage after 28 days of injection. Targeting the minimally invasive surgery strategy, a family of dual pH- and thermo-sensitive hydrogels was developed to be used as a promising drug/cell carrier for catheter based PCI delivery therapy.In the real MI situation, stem cells also suffers from low oxygen and nutrient ischemic local environment and high concentration of cytotoxic substances, which are demonstrated to be main issues tor low long-term engraftment when directly stem cell injection. The second half of this work is to develop hydrogel based stem cell delivery system which can protect cells from initial cytotoxic environment, support cell survival and promote stem cell cardiac differentiation under low nutrient and low oxygen conditions. Anti-oxidant enzyme superoxide dismutase is introduced to protect cells from cytotoxic reactive oxygen species attack. Growth factors like bFGF and IGF1 are loaded or conjugated to hydrogel matrix to support the delivered stem cell survival and differentiation under the low oxygen, low nutrient environment. Furthermore, to prolong the survival and differentiation of stem cells under low oxygen ischemic condition, an oxygen releasing hydrogel system was introduced. 2012-06-22 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1337223886 http://rave.ohiolink.edu/etdc/view?acc_num=osu1337223886 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Materials Science
Myocardial Infarction
Injectable Hydrogel
Stem Cells
spellingShingle Materials Science
Myocardial Infarction
Injectable Hydrogel
Stem Cells
Li, Zhenqing
Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy
author Li, Zhenqing
author_facet Li, Zhenqing
author_sort Li, Zhenqing
title Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy
title_short Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy
title_full Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy
title_fullStr Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy
title_full_unstemmed Development of Multi-functional Stem Cell Delivery Systems for Cardiac Therapy
title_sort development of multi-functional stem cell delivery systems for cardiac therapy
publisher The Ohio State University / OhioLINK
publishDate 2012
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1337223886
work_keys_str_mv AT lizhenqing developmentofmultifunctionalstemcelldeliverysystemsforcardiactherapy
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