scholarly journals Movements of ancient human endogenous retroviruses detected in SOX2-expressing cells

2020 ◽  
Author(s):  
Kazuaki Monde ◽  
Yorifumi Satou ◽  
Mizuki Goto ◽  
Yoshikazu Uchiyama ◽  
Jumpei Ito ◽  
...  
Keyword(s):  
Stem Cells ◽  
Somatic Cells ◽  
Endogenous Retroviruses ◽  
Genome Integrity ◽  
Human Endogenous Retroviruses ◽  
Early Embryos ◽  
Integration Sites ◽  
Induced Pluripotent ◽  
Harmful Effects

SummaryHuman endogenous retroviruses (HERVs) occupy approximately 8% of human genome. HERVs, which are transcribed in early embryos, are epigenetically silenced in somatic cells, except in pathological contexts. HERV-K is thought to protect the embryo from exogenous viral infection. However, uncontrollable HERV-K expression in somatic cells has been implicated in several diseases. Here, we show that SOX2, which plays a key role in maintaining pluripotency of stem cells, is critical for the transcription of HERV-K LTR5Hs. HERV-K can undergo retrotransposition within producer cells in the absence of Env expression. Furthermore, new HERV-K integration sites were identified in a long-term culture of induced pluripotent stem cells, which express SOX2. Together, these results suggest the possibility that the strict dependence of HERV-K on SOX2 have allowed contribution of HERV-K to the protection of early embryos during evolution while limiting potentially harmful effects of HERV-K retrotransposition on host genome integrity to these early embryos.

scholarly journals Development of Multilayer Mesenchymal Stem Cell Cell Sheets

2021 ◽  
Vol 1 (1) ◽  
pp. 4-24
Author(s):  
Jun Ochiai ◽  
Yutaka Niihara ◽  
Joan Oliva
Keyword(s):  
Stem Cells ◽  
Stromal Cells ◽  
Pluripotent Stem Cells ◽  
Cell Sheets ◽  
Gene Therapies ◽  
The Past ◽  
Long Term Effect ◽  
Induced Pluripotent ◽  
New Guidelines

Cell and gene therapies have been developing dramatically over the past decade. To face and adapt to the development of these new therapies, the Food and Drug Administration (FDA) wrote and updated new guidelines from 2016 and keep updating them. Mesenchymal stem cells (MSCs) are the most used cells for treatment, far ahead from the induced pluripotent stem cells (iPSCs), based on registered clinical trials at clinicaltrials.gov. They are widely used because of their differentiation capacity and their anti-inflammatory properties, but some controversies still require clear answers. Additional studies are needed to determine the dosage, the number, and the route of injections (location and transplantation method), and if allogenic MSCs are safe compared to autologous MSC injection, including their long-term effect. In this review, we summarize the research our company is conducting with the adipose stromal cells in engineering cell sheets and their potential application.

scholarly journals Hematopoietic stem/progenitor cells, generation of induced pluripotent stem cells, and isolation of endothelial progenitors from 21- to 23.5-year cryopreserved cord blood

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4773-4777 ◽  
Author(s):  
Hal E. Broxmeyer ◽  
Man-Ryul Lee ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
Nutan Prasain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Induced Pluripotent

Abstract Cryopreservation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) is crucial for cord blood (CB) banking and transplantation. We evaluated recovery of functional HPC cryopreserved as mononuclear or unseparated cells for up to 23.5 years compared with prefreeze values of the same CB units. Highly efficient recovery (80%-100%) was apparent for granulocyte-macrophage and multipotential hematopoietic progenitors, although some collections had reproducible low recovery. Proliferative potential, response to multiple cytokines, and replating of HPC colonies was extensive. CD34+ cells isolated from CB cryopreserved for up to 21 years had long-term (≥ 6 month) engrafting capability in primary and secondary immunodeficient mice reflecting recovery of long-term repopulating, self-renewing HSCs. We recovered functionally responsive CD4+ and CD8+ T lymphocytes, generated induced pluripotent stem (iPS) cells with differentiation representing all 3 germ cell lineages in vitro and in vivo, and detected high proliferative endothelial colony forming cells, results of relevance to CB biology and banking.

In situ generation of human brain organoids on a micropillar array

Lab on a Chip ◽  
2017 ◽  
Vol 17 (17) ◽  
pp. 2941-2950 ◽  
Author(s):  
Yujuan Zhu ◽  
Li Wang ◽  
Hao Yu ◽  
Fangchao Yin ◽  
Yaqing Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Brain ◽  
Pluripotent Stem Cells ◽  
3D Culture ◽  
In Situ Generation ◽  
Induced Pluripotent ◽  
High Throughput Manner

We present a simple and high throughput manner to generate brain organoids in situ from human induced pluripotent stem cells on micropillar arrays and to investigate long-term brain organogenesis in 3D culture in vitro.

scholarly journals Long-Term Stability and Differentiation Potential of Cryopreserved cGMP-Compliant Human Induced Pluripotent Stem Cells

2019 ◽  
Vol 21 (1) ◽  
pp. 108 ◽  
Author(s):  
Mehdi Shafa ◽  
Tylor Walsh ◽  
Krishna Morgan Panchalingam ◽  
Thomas Richardson ◽  
Laura Menendez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Genomic Stability ◽  
Directed Differentiation ◽  
Differentiation Potential ◽  
Long Term Stability ◽  
Induced Pluripotent ◽  
Cell Banks ◽  
2D And 3D

The clinical effectiveness of human induced pluripotent stem cells (iPSCs) is highly dependent on a few key quality characteristics including the generation of high quality cell bank, long-term genomic stability, post-thaw viability, plating efficiency, retention of pluripotency, directed differentiation, purity, potency, and sterility. We have already reported the establishment of iPSC master cell banks (MCBs) and working cell banks (WCBs) under current good manufacturing procedure (cGMP)-compliant conditions. In this study, we assessed the cellular and genomic stability of the iPSC lines generated and cryopreserved five years ago under cGMP-compliant conditions. iPSC lines were thawed, characterized, and directly differentiated into cells from three germ layers including cardiomyocytes (CMs), neural stem cells (NSCs), and definitive endoderm (DE). The cells were also expanded in 2D and 3D spinner flasks to evaluate their long-term expansion potential in matrix-dependent and feeder-free culture environment. All three lines successfully thawed and attached to the L7TM matrix, and formed typical iPSC colonies that expressed pluripotency markers over 15 passages. iPSCs maintained their differentiation potential as demonstrated with spontaneous and directed differentiation to the three germ layers and corresponding expression of specific markers, respectfully. Furthermore, post-thaw cells showed normal karyotype, negative mycoplasma, and sterility testing. These cells maintained both their 2D and 3D proliferation potential after five years of cryopreservation without acquiring karyotype abnormality, loss of pluripotency, and telomerase activity. These results illustrate the long-term stability of cGMP iPSC lines, which is an important step in establishing a reliable, long-term source of starting materials for clinical and commercial manufacturing of iPSC-derived cell therapy products.

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