Accreditation of Biosafe Clinical-Grade Human Embryonic Stem Cells According to Chinese Regulations

Gu, Qi; Wang, Juan; Wang, Lei; Liu, Zheng-Xin; Zhu, Wanwan; Tan, Yunfei; Han, Weifang; Wu, Jun; Feng, Chunjing; Fang, Jie; Liu, Lei; Wang, Liu; Li, Wei; Zhao, Xiaoyang; Hu, Baoyang; Hao, Jie; Zhou, Qi

doi:10.1016/j.stemcr.2017.04.017

Cited by 43 publications

(62 citation statements)

References 42 publications

(51 reference statements)

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“…1A and 1B). The clinical hESC line (Q-CTS-hESC-2) was prepared as described previously 20 . Clinical hESCs were maintained in Essential 8™ basal medium (E8) on vitronectin-coated plates, before dissociation into small clumps to form hEBs for 5 days.…”

Section: Resultsmentioning

confidence: 99%

“…The hESC-derived IMRCs were generated by passaging cells that are migrating out from human embryoid bodies (hEBs), with xeno-free reagents. The clinical hESC line (Q-CTS-hESC-2) was prepared as described previously 20 . Clinical hESCs were maintained in commercially available Essential 8™ (E8) basal medium (Gibco, Carlsbad, MO, USA; A15169-01) with Essential 8™ Supplement (Gibco, A15171-01) on vitronectin-coated plates (1 μg/cm 2 ).…”

Section: Methodsmentioning

confidence: 99%

“…The clinical hESC line (Q-CTS-hESC-2) was prepared as described previously 20 . Clinical hESCs were maintained in the commercially available Essential 8™ (E8) basal medium on vitronectin-coated plates.…”

Section: Methodsmentioning

confidence: 99%

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Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Song

et al. 2020

Preprint

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34Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, 35including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this 36 study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived 37 immunity-and matrix-regulatory cells (IMRCs) manufactured under good manufacturing practice (GMP) 38 requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs through sequentially 39 differentiating hESCs with xeno-free reagents. IMRCs possess a unique gene expression profile distinct 40 from umbilical cord mesenchymal stem cells (UCMSCs), such as higher levels of proliferative, 41 immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both 42 pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the 43 survival rate of the recipient mice in a dose-dependent manner, likely through their paracrine functions. 44IMRCs are superior to both primary UCMSCs and FDA-approved pirfenidone, with an excellent efficacy 45 and safety profile in mice, monkeys and two severely ill COVID-19 patients in our pilot study. In light 46 of recent public health crises involving pneumonia, acute lung injury (ALI) and acute respiratory distress 47 alveolar epithelial cells and capillary endothelial cells caused by various direct and indirect injury factors, 54 resulting in diffuse pulmonary interstitial and alveolar edema, and acute hypoxic respiratory insufficiency. 55Pathophysiologically, its characteristics include decreased lung volume, decreased lung extensibility and 56 imbalance of the ventilation / blood flow ratio. When ALI develops into the severe stage (oxygenation 57 index < 200), it is called acute respiratory distress syndrome (ARDS). Globally, there are more than 3 58 million patients with ARDS annually, accounting for 10% of intensive care unit (ICU) admissions 2 . ALI 59 / ARDS patients have an average mortality rate of 35-46% 3,4 . In late ARDS, pulmonary fibrosis (PF) 60 develops due to persistent alveolar injury, repeated destruction, repair, reconstruction and over-61 deposition of extracellular matrix (ECM) 5 , leading to progressive lung scars and common interstitial 62 pneumonia. In general, idiopathic pulmonary fibrosis (IPF) patients show very poor prognosis, with a 63 median survival time of 3-5 years after diagnosis 6 . It has also been reported that the degree of pulmonary 64 fibrosis is closely related to the mortality of ARDS 7,8 . Importantly, there are still no effective FDA-65 approved drugs to treat ALI, ARDS or IPF hitherto, and most of the experimental drugs are still in Phase 66 II or Phase III studies 2, 9,10 . 67Stem cell therapy is an emerging treatment modality being used to cure various inflammatory and/or 68 degenerative diseases, including ALI and PF. In particular, mesenchymal stem cells (MSCs) have been 69 tested as an intravenous infusion therapy for ALI and PF 11,12 . Preclinical and cl...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Song

et al. 2020

Preprint

Self Cite

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show abstract

“…[34] 、培养基更换频率、细胞培养pH和溶解氧等, 这些参数与干细胞的干性维持和分化状态密切相关 [35,36] . 细胞生产通常采取连续生产方式, 应 [47] , 多个干细胞产品已经在临床上展现出了较好的应用前景 [25] . 如何通过规范性技术指导文件促进干细胞产业健康发展, 将干细胞治疗按照药品规范管理 [27] , 已经…”

Section: 有5×10unclassified

Research progress and regulatory perspectives for stem cell-based regenerative medicine products

Lü¹,

Liu²,

Luo³

2018

Sci. Sin.-Vitae

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Advances in stem cell therapy have led to the surge of regenerative medicine products for treating severe diseases worldwide in the recent years. Stem cells are capable of self-renewal and differentiation, and regenerative medicine products are remarkably complex and varied in their manufacturing processes including methods for cell culture, induction of differentiation and engraftment. The outcomes of the clinical trials of stem cell products also bear uncertainty partly due to the disparities among patients. Therefore it is challenging for the drug administrative agencies to regulate stem cell products. In this article, we review the research progress of the licensed stem cell-based products in the USA, Europe and Japan, along with the regulations and guidance documents of FDA, EMA and PMDA. We also summarize the considerations in evaluating the Chemistry, Manufacture and Control section of stem cell product applications. We hope our effort would contribute to the establishment of science-based regulatory policy in China, and provide the insights for the development and evaluation of regenerative medicine products. regenerative medicine products, stem cell, mesenchymal stem cell, embryonic stem cell, induced pluripotent stem cell, cell therapy, drug evaluation

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“…Recipes free of proteins are particularly preferred for the manufacture of clinical-grade cells for therapy. We and colleagues have developed xeno-free hESCs with defined quality characteristics fitting for clinical therapy ( Gu et al., 2017 ). To generate MSNs from these clinical-grade hESCs, we invented a small-molecule-based recipe and a streamlined protocol for efficient induction of lateral ganglionic eminence (LGE)-like cells and MSNs.…”

Section: Introductionmentioning

confidence: 99%

A Chemical Recipe for Generation of Clinical-Grade Striatal Neurons from hESCs

Zhang

et al. 2018

Stem Cell Reports

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SummaryDifferentiation of human pluripotent stem cells (hPSCs) into striatal medium spiny neurons (MSNs) promises a cell-based therapy for Huntington's disease. However, clinical-grade MSNs remain unavailable. Here, we developed a chemical recipe named XLSBA to generate clinical-grade MSNs from embryonic stem cells (ESCs). We introduced the γ-secretase inhibitor DAPT into the recipe to accelerate neural differentiation, and replaced protein components with small molecules. Using this optimized protocol we could efficiently direct regular human ESCs (hESCs) as well as clinical-grade hESCs to lateral ganglionic eminence (LGE)-like progenitors and striatal MSNs within less than half of the time than previous protocols (within 14 days and 21 days, respectively). These striatal cells expressed appropriate MSN markers and electrophysiologically acted like authentic MSNs. Upon transplantation into brains of neonatal mice or mouse model of Huntington's disease, they exhibited sufficient safety and reasonable efficacy. Therefore, this quick and highly efficient derivation of MSNs offers unprecedented access to clinical application.

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Accreditation of Biosafe Clinical-Grade Human Embryonic Stem Cells According to Chinese Regulations

Cited by 43 publications

References 42 publications

Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Research progress and regulatory perspectives for stem cell-based regenerative medicine products

A Chemical Recipe for Generation of Clinical-Grade Striatal Neurons from hESCs

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