Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells

Treatment of central nervous system (CNS) malignancies typically involves radiotherapy to forestall tumor growth and recurrence following surgical resection. Despite the many benefits of cranial radiotherapy, survivors often suffer from a wide range of debilitating and progressive cognitive deficits. Thus, while patients afflicted with primary and secondary malignancies of the CNS now experience longer local regional control and progression-free survival, there remains no clinical recourse for the unintended neurocognitive sequelae associated with their cancer treatments. Multiple mechanisms contribute to disrupted cognition following irradiation, including the depletion of radiosensitive populations of stem and progenitor cells in the hippocampus. We have explored the potential of using intrahippocampal transplantation of human stem cells to ameliorate radiation-induced cognitive dysfunction. Past studies demonstrated the capability of cranially transplanted human embryonic (hESCs) and neural (hNSCs) stem cells to functionally restore cognition in rats 1 and 4 months after cranial irradiation. The present study employed an FDA-approved fetal-derived hNSC line capable of large scale-up under good manufacturing practice (GMP). Animals receiving cranial transplantation of these cells 1 month following irradiation showed improved hippocampal spatial memory and contextual fear conditioning performance compared to irradiated, sham surgery controls. Significant newly born (doublecortin positive) neurons and a smaller fraction of glial subtypes were observed within and nearby the transplantation core. Engrafted cells migrated and differentiated into neuronal and glial subtypes throughout the CA1 and CA3 subfields of the host hippocampus. These studies expand our prior findings to demonstrate that transplantation of fetal-derived hNSCs improves cognitive deficits in irradiated animals, as assessed by two separate cognitive tasks.

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Single-Use Bioreactors for Human Pluripotent and Adult Stem Cells: Towards Regenerative Medicine Applications

Bioengineering ◽

10.3390/bioengineering8050068 ◽

2021 ◽

Vol 8 (5) ◽

pp. 68

Author(s):

Diogo E.S. Nogueira ◽

Joaquim M.S. Cabral ◽

Carlos A.V. Rodrigues

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Regenerative Medicine ◽

Large Scale ◽

Adult Stem Cells ◽

Regulatory Agencies ◽

Human Stem Cells ◽

Stem Cell Expansion ◽

Single Use

Research on human stem cells, such as pluripotent stem cells and mesenchymal stromal cells, has shown much promise in their use for regenerative medicine approaches. However, their use in patients requires large-scale expansion systems while maintaining the quality of the cells. Due to their characteristics, bioreactors have been regarded as ideal platforms to harbour stem cell biomanufacturing at a large scale. Specifically, single-use bioreactors have been recommended by regulatory agencies due to reducing the risk of product contamination, and many different systems have already been developed. This review describes single-use bioreactor platforms which have been used for human stem cell expansion and differentiation, along with their comparison with reusable systems in the development of a stem cell bioprocess for clinical applications.

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Microcarrier-based systems for the large-scale expansion of human stem cellS

Cytotherapy ◽

10.1016/j.jcyt.2015.03.587 ◽

2015 ◽

Vol 17 (6) ◽

pp. S80

Author(s):

Mark S. Szczypka ◽

Dave Splan ◽

Grishma Patel ◽

Heather Woolls

Keyword(s):

Stem Cells ◽

Large Scale ◽

Human Stem Cells ◽

Scale Expansion

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Comparative RNAi Screens in Isogenic Human Stem Cells RevealSMARCA4as a Differential Regulator

10.1101/500181 ◽

2018 ◽

Author(s):

Ceren Güneş ◽

Maciej Paszkowski-Rogacz ◽

Susann Rahmig ◽

Shahryar Khattak ◽

Martin Wermke ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Biology ◽

Large Scale ◽

Model Organisms ◽

Human Stem Cells ◽

Cell Type ◽

Hematopoietic Stem ◽

Neural Lineage ◽

Powerful Approach

SUMMARYLarge-scale RNAi screens are a powerful approach to identify functions of genes in a cell-type specific manner. For model organisms, genetically identical (isogenic) cells from different cell-types are readily available, making comparative studies meaningful. For humans, however, screening isogenic cells is not straightforward. Here, we show that RNAi screens are possible in genetically identical human stem cells, employing induced pluripotent stem cell as intermediates. The screens revealedSMARCA4(SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4) as a stemness regulator, while balancing differentiation distinctively for each cell type.SMARCA4knockdown in hematopoietic stem progenitor cells (HSPC) caused impaired self-renewalin-vitroandin-vivowith skewed myeloid differentiation; whereas in neural stem cells (NSC), it impaired selfrenewal while biasing differentiation towards neural lineage, through combinatorial SWI/SNF subunit assembly. Our findings pose a powerful approach for deciphering human stem cell biology and attribute distinct roles toSMARCA4in stem cell maintenance.

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