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A Nano-In-Micro System for Enhanced Stem Cell Therapy of Ischemic Diseases.

ABSTRACT: Stem cell therapy holds great potential for treating ischemic diseases. However, contemporary methods for local stem cell delivery suffer from poor cell survival/retention after injection. We developed a unique multiscale delivery system by encapsulating therapeutic agent-laden nanoparticles in alginate hydrogel microcapsules and further coentrapping the nano-in-micro capsules with stem cells in collagen hydrogel. The multiscale system exhibits significantly higher mechanical strength and stability than pure collagen hydrogel. Moreover, unlike nanoparticles, the nano-in-micro capsules do not move with surrounding body fluid and are not taken up by the cells. This allows a sustained and localized release of extracellular epidermal growth factor (EGF), a substance that could significantly enhance the proliferation of mesenchymal stem cells while maintaining their multilineage differentiation potential via binding with its receptors on the stem cell surface. As a result, the multiscale system significantly improves the stem cell survival at 8 days after implantation to ?70% from ?4-7% for the conventional system with nanoparticle-encapsulated EGF or free EGF in collagen hydrogel. After injecting into the ischemic limbs of mice, stem cells in the multiscale system facilitate tissue regeneration to effectively restore ?100% blood perfusion in 4 weeks without evident side effects.

SUBMITTER: Wang H

PROVIDER: S-EPMC5571461 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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A Nano-In-Micro System for Enhanced Stem Cell Therapy of Ischemic Diseases.

Wang Hai H Agarwal Pranay P Xiao Yichao Y Peng Hao H Zhao Shuting S Liu Xuanyou X Zhou Shenghua S Li Jianrong J Liu Zhenguo Z He Xiaoming X

ACS central science 20170719 8

Stem cell therapy holds great potential for treating ischemic diseases. However, contemporary methods for local stem cell delivery suffer from poor cell survival/retention after injection. We developed a unique multiscale delivery system by encapsulating therapeutic agent-laden nanoparticles in alginate hydrogel microcapsules and further coentrapping the nano-in-micro capsules with stem cells in collagen hydrogel. The multiscale system exhibits significantly higher mechanical strength and stabil ...[more]

PMID: 28852702

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Project description:BackgroundAlthough the use of cardiac patches is still controversial, cardiac patch has the significance in the field of the tissue engineered cardiac regeneration because it overcomes several shortcomings of intra-myocardial injection by providing a template for cells to form a cohesive sheet. So far, fibrous scaffolds fabricated using electrospinning technique have been increasingly explored for preparation of cardiac patches. One of the problems with the use of electrospinning is that nanofibrous structures hardly allow the infiltration of cells for development of 3D tissue construct. In this respect, we have prepared novel bi-modal electrospun scaffolds as a feasible strategy to address the challenges in cardiac tissue engineering .MethodsNano/micro bimodal composite fibrous patch composed of collagen and poly (D, L-lactic-co-glycolic acid) (Col/PLGA) was fabricated using an independent nozzle control multi-electrospinning apparatus, and its feasibility as the stem cell laden cardiac patch was systemically investigated.ResultsNano/micro bimodal distributions of Col/PLGA patches without beaded fibers were obtained in the range of the 4-6% collagen concentration. The poor mechanical properties of collagen and the hydrophobic property of PLGA were improved by co-electrospinning. In vitro experiments using bone marrow-derived mesenchymal stem cells (BMSCs) revealed that Col/PLGA showed improved cyto-compatibility and proliferation capacity compared to PLGA, and their extent increased with increase in collagen content. The results of tracing nanoparticle-labeled as well as GFP transfected BMSCs strongly support that Col/PLGA possesses the long-term stem cells retention capability, thereby allowing stem cells to directly function as myocardial and vascular endothelial cells or to secrete the recovery factors, which in turn leads to improved heart function proved by histological and echocardiographic findings.ConclusionCol/PLGA bimodal cardiac patch could significantly attenuate cardiac remodeling and fully recover the cardiac function, as a consequence of their potent long term stem cell engraftment capability.

Dataset Information

A Nano-In-Micro System for Enhanced Stem Cell Therapy of Ischemic Diseases.

Publications

A Nano-In-Micro System for Enhanced Stem Cell Therapy of Ischemic Diseases.

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