Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction

Zhao, Shuting; Xu, Zhaobin; Wang, Hai; Reese, Benjamin E.; Gushchina, Liubov V.; Jiang, Min; Agarwal, Pranay; Xu, Jiangsheng; Zhang, Mingjun; Shen, Rulong; Liu, Zhenguo; Weisleder, Noah; He, Xiaoming

doi:10.1038/ncomms13306

Cited by 101 publications

(122 citation statements)

References 59 publications

(116 reference statements)

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“…To address this issue in other systems, a variety of natural and synthetic 3D culture systems have been developed [55,56,57,58,59]. 3D hydrogels have also been recently used to study biophysical regulation of encapsulated NSCs.…”

Section: Recent Advanced Materials To Probe and Control Nsc Mechanotrmentioning

confidence: 99%

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

Kang

Kumar

Schaffer

2017

Current Opinion in Biomedical Engineering

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Neural stem cells (NSCs) are a valuable cell source for tissue engineering, regenerative medicine, disease modeling, and drug screening applications. Analogous to other stem cells, NSCs are tightly regulated by their microenvironmental niche, and prior work utilizing NSCs as a model system with engineered biomaterials has offered valuable insights into how biophysical inputs can regulate stem cell proliferation, differentiation, and maturation. In this review, we highlight recent exciting studies with innovative material platforms that enable narrow stiffness gradients, mechanical stretching, temporal stiffness switching, and three-dimensional culture to study NSCs. These studies have significantly advanced our knowledge of how stem cells respond to an array of different biophysical inputs and the underlying mechanosensitive mechanisms. In addition, we discuss efforts to utilize engineered material scaffolds to improve NSC-based translational efforts and the importance of mechanobiology in tissue engineering applications.

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Section: Recent Advanced Materials To Probe and Control Nsc Mechanotrmentioning

confidence: 99%

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

Kang

Kumar

Schaffer

2017

Current Opinion in Biomedical Engineering

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“…We took a bioinspired procedure mimicking that used by nature (Fig. 1) to prepare totipotent-pluripotent stem cells for implantation in the uterus, to address this grand challenge using biomaterials systems with the bioinspired spatial and temporal complexities 29 . As shown in Fig.…”

Section: Cardiac Regeneration Using Microscale Biomaterials Systems Wmentioning

confidence: 99%

“…5C), minimizes inflammatory responses to the injected cells (Fig. 5D), and eliminates the notorious issue of teratoma formation associated with directly injecting pluripotent stem cells 29 . As a result, it significantly reduces fibrosis (Fig.…”

Section: Cardiac Regeneration Using Microscale Biomaterials Systems Wmentioning

confidence: 99%

Microscale Biomaterials with Bioinspired Complexity of Early Embryo Development and in the Ovary for Tissue Engineering and Regenerative Medicine

2016

ACS Biomater. Sci. Eng.

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Tissue engineering and regenerative medicine (TERM) are attracting more and more attention for treating various diseases in modern medicine. Various biomaterials including hydrogels and scaffolds have been developed to prepare cells (particularly stem cells) and tissues under 3D conditions for TERM applications. Although these biomaterials are usually homogeneous in early studies, effort has been made recently to generate biomaterials with the spatiotemporal complexities present in the native milieu of the specific cells and tissues under investigation. In this communication, the microfluidic and coaxial electrospray approaches that we used for generating microscale biomaterials with the spatial complexity of both pre-hatching embryos and ovary in the female reproductive system were introduced. This is followed by an overview of our recent work on applying the resultant bioinspired biomaterials for cultivation of normal and cancer stem cells, regeneration of cardiac tissue, and culture of ovarian follicles. The cardiac regeneration studies show the importance of using different biomaterials to engineer stem cells at different stages (i.e., in vitro culture versus in vivo implantation) for tissue regeneration. All the studies demonstrate the merit of accounting for bioinspired complexities in engineering cells and tissues for TERM applications.

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“…[5, 6] It has shown great promise for treating various diseases including diabetes, hemophilia, cancer, liver and renal failure, as well as cardiovascular diseases. [5–7] Cryopreservation of microencapsulated cells make it possible for their wide distribution to end users so that they are readily available when needed for transplantation. [2, 3, 5, 8] It also offers a powerful tool for the integration of cell expansion and cryopreservation.…”

Section: Introductionmentioning

confidence: 99%

“…[32, 33, 35, 36] For example, core-shell structured encapsulation has been reported to better support 3D culture (providing minimized spontaneous differentiation of stem cells encapsulated in the core [4, 32, 34] ) and transplantation. [33, 37] In addition, the use of the large microcapsules may allow for rapidly processing a large volume (tens to hundreds of milliliters) of cell suspensions (which is needed for cytotherapy or cell transplantation [38] ). However, vitreous cryopreservation of cells encapsulated in large-volume microcapsules (> 500 μm in diameter) with a core-shell structure has not been done.…”

Section: Introductionmentioning

confidence: 99%

Hydrogel Encapsulation Facilitates Rapid‐Cooling Cryopreservation of Stem Cell‐Laden Core–Shell Microcapsules as Cell–Biomaterial Constructs

Zhao

Liu

Zhu

et al. 2017

Adv Healthcare Materials

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Core-shell structured stem cell microencapsulation in hydrogel has wide applications in tissue engineering, regenerative medicine, and cell-based therapies because it offers an ideal immunoisolative microenvironment for cell delivery and 3D culture and differentiation. Long-term storage of such microcapsules as cell-biomaterial constructs by cryopreservation is an enabling technology for their wide distribution and ready availability for clinical transplantation. However, most of the existing studies focused on cryopreservation of separated cells or cells in microcapsules without a core-shell structure (i.e., hydrogel beads). The goal of this study is to achieve cryopreservation of stem cells encapsulated in core-shell microcapsules as cell-biomaterial constructs or biocomposites. To this end, a capillary microfluidics-based core-shell alginate hydrogel encapsulation technology is developed to facilitate cryopreservation of porcine adipose-derived stem cells (pADSCs) laden microcapsules with very low concentration (2 mol L−1) of cell membrane penetrating cryoprotective agents (CPAs) by suppressing ice formation. This may provide a low-CPA and cost-effective approach for vitreous cryopreservation of “ready-to-use” stem cell-biomaterial constructs, facilitating their off-the-shelf availability and widespread applications.

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Bioengineering of injectable encapsulated aggregates of pluripotent stem cells for therapy of myocardial infarction

Cited by 101 publications

References 59 publications

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

Microscale Biomaterials with Bioinspired Complexity of Early Embryo Development and in the Ovary for Tissue Engineering and Regenerative Medicine

Hydrogel Encapsulation Facilitates Rapid‐Cooling Cryopreservation of Stem Cell‐Laden Core–Shell Microcapsules as Cell–Biomaterial Constructs

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