Stem Cell
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2021 ◽  
Vol 123 (8) ◽  
pp. 151796
Sen Tang ◽  
Tao Tang ◽  
Guicheng Gao ◽  
Qiangqiang Wei ◽  
Kuo Sun ◽  

2021 ◽  
Vol 2 (4) ◽  
pp. 100859
Joe Z. Zhang ◽  
Shane Rui Zhao ◽  
Chengyi Tu ◽  
Paul Pang ◽  
Mao Zhang ◽  

Drugs in R&D ◽  
2021 ◽  
Kimitaka Suetsugu ◽  
Shota Muraki ◽  
Junshiro Fukumoto ◽  
Ryosuke Matsukane ◽  
Yasuo Mori ◽  

2021 ◽  
Vol 60 (20) ◽  
pp. 3299-3304
Yuta Kaito ◽  
Shunsuke Yui ◽  
Kazuki Inai ◽  
Daishi Onai ◽  
Ryosuke Kinoshita ◽  

2021 ◽  
Vol 12 (1) ◽  
Franziska Olm ◽  
Lena Panse ◽  
Josefina H. Dykes ◽  
Daniel Bexell ◽  
Thomas Laurell ◽  

Abstract Background Graft-contaminating tumor cells correlate with inferior outcome in high-risk neuroblastoma patients undergoing hematopoietic stem cell transplantation and can contribute to relapse. Motivated by the potential therapeutic benefit of tumor cell removal as well as the high prognostic and diagnostic value of isolated circulating tumor cells from stem cell grafts, we established a label-free acoustophoresis-based microfluidic technology for neuroblastoma enrichment and removal from peripheral blood progenitor cell (PBPC) products. Methods Neuroblastoma patient-derived xenograft (PDX) cells were spiked into PBPC apheresis samples as a clinically relevant model system. Cells were separated by ultrasound in an acoustophoresis microchip and analyzed for recovery, purity and function using flow cytometry, quantitative real-time PCR and cell culture. Results PDX cells and PBPCs showed distinct size distributions, which is an important parameter for efficient acoustic separation. Acoustic cell separation did not affect neuroblastoma cell growth. Acoustophoresis allowed to effectively separate PDX cells from spiked PBPC products. When PBPCs were spiked with 10% neuroblastoma cells, recoveries of up to 98% were achieved for PDX cells while more than 90% of CD34+ stem and progenitor cells were retained in the graft. At clinically relevant tumor cell contamination rates (0.1 and 0.01% PDX cells in PBPCs), neuroblastoma cells were depleted by more than 2-log as indicated by RT-PCR analysis of PHOX2B, TH and DDC genes, while > 85% of CD34+ cells could be retained in the graft. Conclusion These results demonstrate the potential use of label-free acoustophoresis for PBPC processing and its potential to develop label-free, non-contact tumor cell enrichment and purging procedures for future clinical use.

2021 ◽  
cuilan hou ◽  
Xunwei jiang ◽  
Qingzhu Qiu ◽  
Junmin Zheng ◽  
Shujia Lin ◽  

Catecholaminergic polymorphic ventricular tachycardia (CPVT) has been considered as one of the most important causes of children's sudden cardiac death. Mutations in the genes for RyR2 and CASQ2, two mainly subtypes of CPVT, have been identified. However, the mutation in the gene of TECRL was rarely reported, which could be another genetic cause of CPVT. We evaluated myocardial contractility, electrophysiology, calcium handling in Tecrl knockout (Tecrl KO) mice and human induced pluripotent stem cell-derived cardiomyocytes. Immediately after epinephrine plus caffeine injection, Tecrl KO mice showed much more multiple premature ventricular beats and ventricular tachycardia. The Tecrl KO mice demonstrate CPVT phenotypes. Mechanistically, intracellular calcium amplitude was reduced, while time to baseline of 50 was increased in acute isolated cardiomyocytes. RyR2 protein levels decreased significantly upon cycloheximide treatment in TECRL deficiency cardiomyocytes. Overexpression of TECRL and KN93 can partially reverse cardiomyocytes calcium dysfunction, and this is p-CaMKII/CaMKII dependent. Therefore, a new CPVT mouse model was constructed. We propose a previously unrecognized mechanism of TECRL and provide support for the therapeutic targeting of TECRL in treating CPVT

2021 ◽  
Vol 3 ◽  
Athina Samara ◽  
Branson D. Belle

The COVID-19 pandemic underlined that by investing in both basic and clinical life science research and if there are enough volunteers, it is feasible to have -validated by Phase III clinical trials- vaccines in less than a year. Regarding the treatment options for the people who were infected by COVID-19, we know that it was the large clinical trials - like SOLIDARITY (WHO) and RECOVERY (UK)- that gave the most valid results, and that although hundreds of drugs were repurposed, sadly, most proved to be unsuccessful. Repurposing drugs and compassionate use, were the only options for the first half of 2020. The same applied to the convalescent plasma (CP) approach; however, apart from CP, other cell derived therapeutics were deployed, such as synthetic monoclonal antibodies, which were also tested and given provisional licences by health authorities. Unfortunately, synthetic antibody production comes with problems related to low and slow yield that were not overcome, while SARS-CoV-2 viral mutations may possibly render them less effective. One approach that works and is currently assessed in several clinical trials, is mesenchymal stromal cell (MSCs) and extracellular vesicle (EV) administration for therapy. Interdisciplinarity may prove key here. Easy to produce nanomaterials and biomaterials should be further investigated to increase bioproduction of MSCs, both at the level of therapeutics, as the base substrate for EV production and to upscale synthetic antibody production for therapy.

2021 ◽  
Vol 8 ◽  
Jan Adamowicz ◽  
Luis Alex Kluth ◽  
Marta Pokrywczynska ◽  
Tomasz Drewa

Tissue engineering offers the possibility to overcome limitations of current management for postprostatectomy incontinence and ED. Developed in recent years biotechnological feasibility of mesenchymal stem cell isolation, in vitro cultivation and implantation became the basis for new cell-based therapies oriented to induce regeneration of adult tissue. The perspective to offer patients suffering from post-prostatectomy incontinence or erectile dysfunction minimal invasive one-time procedure utilizing autologous stem cell transplantation is desired management.

Biology Open ◽  
2021 ◽  
Vol 10 (10) ◽  
Aaron M. Savage ◽  
Ramiro Alberio ◽  
Andrew D. Johnson

ABSTRACT In vitro production of tissue-specific stem cells [e.g. haematopoietic stem cells (HSCs)] is a key goal of regenerative medicine. However, recent efforts to produce fully functional tissue-specific stem cells have fallen short. One possible cause of shortcomings may be that model organisms used to characterize basic vertebrate embryology (Xenopus, zebrafish, chick) may employ molecular mechanisms for stem cell specification that are not conserved in humans, a prominent example being the specification of primordial germ cells (PGCs). Germ plasm irreversibly specifies PGCs in many models; however, it is not conserved in humans, which produce PGCs from tissue termed germline-competent mesoderm (GLCM). GLCM is not conserved in organisms containing germ plasm, or even in mice, but understanding its developmental potential could unlock successful production of other stem cell types. GLCM was first discovered in embryos from the axolotl and its conservation has since been demonstrated in pigs, which develop from a flat-disc embryo like humans. Together these findings suggest that GLCM is a conserved basal trait of vertebrate embryos. Moreover, the immortal nature of germ cells suggests that immortality is retained during GLCM specification; here we suggest that the demonstrated pluripotency of GLCM accounts for retention of immortality in somatic stem cell types as well. This article has an associated Future Leaders to Watch interview with the author of the paper.

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2748
Tohid Siddiqui ◽  
Prabesh Bhattarai ◽  
Stanislava Popova ◽  
Mehmet Ilyas Cosacak ◽  
Sanjeev Sariya ◽  

Neurogenesis decreases in Alzheimer’s disease (AD) patients, suggesting that restoring the normal neurogenic response could be a disease modifying intervention. To study the mechanisms of pathology-induced neuro-regeneration in vertebrate brains, zebrafish is an excellent model due to its extensive neural regeneration capacity. Here, we report that Kynurenic acid (KYNA), a metabolite of the amino acid tryptophan, negatively regulates neural stem cell (NSC) plasticity in adult zebrafish brain through its receptor, aryl hydrocarbon receptor 2 (Ahr2). The production of KYNA is suppressed after amyloid-toxicity through reduction of the levels of Kynurenine amino transferase 2 (KAT2), the key enzyme producing KYNA. NSC proliferation is enhanced by an antagonist for Ahr2 and is reduced with Ahr2 agonists or KYNA. A subset of Ahr2-expressing zebrafish NSCs do not express other regulatory receptors such as il4r or ngfra, indicating that ahr2-positive NSCs constitute a new subset of neural progenitors that are responsive to amyloid-toxicity. By performing transcriptome-wide association studies (TWAS) in three late onset Alzheimer disease (LOAD) brain autopsy cohorts, we also found that several genes that are components of KYNA metabolism or AHR signaling are differentially expressed in LOAD, suggesting a strong link between KYNA/Ahr2 signaling axis to neurogenesis in LOAD.

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