Generation of cardiac spheres from primate pluripotent stem cells in a small molecule-based 3D system

Jiang, Bin; Xiang, Zhen; Ai, Zongyong; Wang, Hong; Li, Yanjiao; Ji, Weizhi; Li, Tianqing

doi:10.1016/j.biomaterials.2015.06.024

Cited by 29 publications

(31 citation statements)

References 37 publications

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“…1A). When cultured in ultra-low dishes, spheres rarely formed big clumps, and, after being transferred to culture bags, 1% methylcellulose in the medium could prevent clump formation by increasing viscosity 19,24 . Subculturing is also an essential step for robust hESC expansion.…”

Section: Discussionmentioning

confidence: 99%

“…By utilizing ultra-low attachement dish, which have low attachment for cells 23 , we obtained optimized seeding density and culture medium, established a 3D culture system with single-cell hESCs for initial seeding, and produced cells in aggregates for proliferation. Then we progressively scaled up the system to cell culture bags while employing methylcellulose to prevent cell conglobation 19,24 , and finally reached a yield of 1.5 × 10 9 cells per 1.5-L culture system. Importantly, hESCs maintained normal morphology and pluripotency for more than 30 passages in the 3D culture system.…”

Section: Introductionmentioning

confidence: 99%

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A fully defined static suspension culture system for large-scale human embryonic stem cell production

et al. 2018

Cell Death Dis

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Human embryonic stem cells (hESCs) play an important role in regenerative medicine due to their potential to differentiate into various functional cells. However, the conventional adherent culture system poses challenges to mass production of high-quality hESCs. Though scientists have made many attempts to establish a robust and economical hESC suspension culture system, there are existing limitations, including suboptimal passage methods and shear force caused by dynamic stirring. Here, we report on an efficient large-scale culture system, which enables long-term, GMP grade, single-cell inoculation, and serial expansion of hESCs with a yield of about 1.5 × 109 cells per 1.5-L culture, while maintaining good pluripotency. The suspension culture system was enlarged gradually from a 100-mm dish to a 1.8-L culture bag with methylcellulose involvement to avoid sphere fusion. Under the optimal experimental protocol, this 3D system resolves current problems that limit mass production and clinical application of hESCs, and thus can be used in commercial-level hESC production for cell therapy and pharmaceutics screening in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A fully defined static suspension culture system for large-scale human embryonic stem cell production

et al. 2018

Cell Death Dis

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“…PSCs may prove to be better since they have excellent proliferation and a shorter doubling time than adult stem cells. Moreover, in a 3D spheroid culture system, the PSCs may be propagated to 1 × 10 6 cells/ml in a 200‐ml plastic bag within 5 days when ∼2 × 10 8 cells in spheroids could be obtained . Kempf et al.…”

Section: Cell‐based Therapies For MImentioning

confidence: 99%

“…PSCs have enormous value as a tool for drug screening and tissue engineering/regeneration . Compared with animal models, PSCs can reduce animal usage and can gain more veridical data that better mimics in vivo conditions in the human body.…”

Section: Cell‐based Therapies For MImentioning

confidence: 99%

Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Jiang

Shamul

et al. 2020

Advanced Therapeutics

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Myocardial infarction (MI) is a life‐threatening disease resulting from the irreversible death of cardiomyocytes (CMs). Stem cell‐based therapies have been studied for MI treatment over the last two decades with promising outcomes. Here, the past work in this field is critically reviewed to elucidate the advantages and disadvantages of treating MI using pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), adult stem cells, and cardiac progenitor cells. Overall, PSCs (particularly iPSCs) have more advantages than the other cells for cardiac regeneration. However, the use of iPSCs is also facing critical challenges, which may be resolved by using biomaterials to engineer stem cells for reduced immunogenicity, improved immobilization/survival in the heart, and increased integration with the host cardiac tissue to eliminate arrhythmia. Biomaterials have also been applied in the derivation of CMs in vitro to increase the efficiency and maturation of cardiac differentiation. Collectively, a lot has been learned from the past failures of simply injecting intact stem cells or their derivatives in vivo for treating MI, and bioengineering stem cells with biomaterials may be a valuable strategy for advancing stem cell therapy towards its widespread application for MI treatment in the clinic.

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“…Thus, differential levels of SHH signaling, in combination with other signaling such as Wnt and retinoic acid, influence neural regional specification of hPSCs into forebrain cortical tissues, midbrain tissues, and hindbrain/spinal cord tissues [6]. In biomaterials research, one attractive approach is to modulate hPSC fate decisions and differentiations using small molecules that regulate signaling pathways through defined mechanisms [26][27][28][29]. Specifically, small molecules in SHH signaling [25,30] have been demonstrated previously to facilitate the generation of some specific neural types from hPSCs [31].…”

Section: Introductionmentioning

confidence: 99%

Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses

et al. 2016

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Generation of cardiac spheres from primate pluripotent stem cells in a small molecule-based 3D system

Cited by 29 publications

References 37 publications

A fully defined static suspension culture system for large-scale human embryonic stem cell production

A fully defined static suspension culture system for large-scale human embryonic stem cell production

Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses

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