Role of Adult Tissue-Derived Pluripotent Stem Cells in Bone Regeneration

Abstract Background Bone marrow-derived mononuclear cells (BM-MNC) consist of a heterogeneous mix of mesenchymal stem cells (MSC), hematopoietic progenitor cells (HPC), endothelial progenitor cells (EPC), monocytes, lymphocytes and pluripotent stem cells. Whereas the importance of MSC and EPC has been well documented in bone healing and regeneration studies, the role of pluripotent stem cells is still poorly understood. In the present study we evaluated if and how Very Small Embryonic Like cells (VSEL), isolated from rat BM-MNC, contribute to bone healing. Methods Large bone defects were made in the femurs of 38 Sprague Dawley female rats and treated with β-TCP scaffold granules seeded with male VSEL; BM-MNC, VSEL-depleted BM-MNC or scaffold alone, and bone healing was evaluated at 8 weeks post-surgery. Results Bone healing was significantly increased in defects treated with VSEL and BM-MNC, compared to defects treated with VSEL-depleted BM-MNC. Donor cells were detected in new bone tissue, in all the defects treated with cells, and in fibrous tissue only in defects treated with VSEL-depleted BM-MNC. The number of CD68+ cells was the highest in the VSEL-depleted group, whereas the number of TRAP positive cells was the lowest in this group. Conclusions Based on the results, we can conclude that VSEL play a role in BM-MNC induced bone formation. In our rat femur defect model, in defects treated with VSEL-depleted BM-MNC, osteoclastogenesis and bone formation were decreased, and foreign body reaction was increased.

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Transcriptional landscape of myogenesis from human pluripotent stem cells reveals a key role of TWIST1 in maintenance of skeletal muscle progenitors

eLife ◽

10.7554/elife.46981 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

In Young Choi ◽

Hotae Lim ◽

Hyeon Jin Cho ◽

Yohan Oh ◽

Bin-Kuan Chou ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Progenitor Cells ◽

Pluripotent Stem Cells ◽

Expression Profiles ◽

Human Pluripotent Stem Cells ◽

Knock Out ◽

Muscle Progenitor Cells ◽

Transcriptional Landscape

Generation of skeletal muscle cells with human pluripotent stem cells (hPSCs) opens new avenues for deciphering essential, but poorly understood aspects of transcriptional regulation in human myogenic specification. In this study, we characterized the transcriptional landscape of distinct human myogenic stages, including OCT4::EGFP+ pluripotent stem cells, MSGN1::EGFP+ presomite cells, PAX7::EGFP+ skeletal muscle progenitor cells, MYOG::EGFP+ myoblasts, and multinucleated myotubes. We defined signature gene expression profiles from each isolated cell population with unbiased clustering analysis, which provided unique insights into the transcriptional dynamics of human myogenesis from undifferentiated hPSCs to fully differentiated myotubes. Using a knock-out strategy, we identified TWIST1 as a critical factor in maintenance of human PAX7::EGFP+ putative skeletal muscle progenitor cells. Our data revealed a new role of TWIST1 in human skeletal muscle progenitors, and we have established a foundation to identify transcriptional regulations of human myogenic ontogeny (online database can be accessed in http://www.myogenesis.net/).

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3,2′-Dihydroxyflavone Improves the Proliferation and Survival of Human Pluripotent Stem Cells and Their Differentiation into Hematopoietic Progenitor Cells

Journal of Clinical Medicine ◽

10.3390/jcm9030669 ◽

2020 ◽

Vol 9 (3) ◽

pp. 669 ◽

Cited By ~ 1

Author(s):

Kyeongseok Kim ◽

Ahmed Abdal Dayem ◽

Minchan Gil ◽

Gwang-Mo Yang ◽

Soo Bin Lee ◽

...

Keyword(s):

Stem Cells ◽

Progenitor Cells ◽

Pluripotent Stem Cells ◽

Mononuclear Cells ◽

Nk Cell ◽

Human Pluripotent Stem Cells ◽

Hematopoietic Progenitor Cells ◽

Hematopoietic Progenitor ◽

Differentiation Potential ◽

Proliferation And Differentiation

Efficient maintenance of the undifferentiated status of human pluripotent stem cells (hiPSCs) is crucial for producing cells with improved proliferation, survival and differentiation, which can be successfully used for stem cell research and therapy. Here, we generated iPSCs from healthy donor peripheral blood mononuclear cells (PBMCs) and analyzed the proliferation and differentiation capacities of the generated iPSCs using single cell NGS-based 24-chromosome aneuploidy screening and RNA sequencing. In addition, we screened various natural compounds for molecules that could enhance the proliferation and differentiation potential of hiPSCs. Among the tested compounds, 3,2′-dihydroxyflavone (3,2′-DHF) significantly increased cell proliferation and expression of naïve stemness markers and decreased the dissociation-induced apoptosis of hiPSCs. Of note, 3,2′-DHF-treated hiPSCs showed upregulation of intracellular glutathione (GSH) and an increase in the percentage of GSH-high cells in an analysis with a FreSHtracer system. Interestingly, culture of the 3,2′-DHF-treated hiPSCs in differentiation media enhanced their mesodermal differentiation and differentiation into CD34+ CD45+ hematopoietic progenitor cells (HPC) and natural killer cells (NK) cells. Taken together, our results demonstrate that the natural compound 3,2′-DHF can improve the proliferation and differentiation capacities of hiPSCs and increase the efficiency of HPC and NK cell production from hiPSCs.

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Brain-derived neurotrophic factor increases cell number of neural progenitor cells derived from human induced pluripotent stem cells

PeerJ ◽

10.7717/peerj.11388 ◽

2021 ◽

Vol 9 ◽

pp. e11388

Author(s):

Panetha Pansri ◽

Phetcharat Phanthong ◽

Nopparat Suthprasertporn ◽

Yindee Kitiyanant ◽

Alisa Tubsuwan ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Induced Pluripotent Stem Cells ◽

Progenitor Cells ◽

Pluripotent Stem Cells ◽

Neurotrophic Factor ◽

Neural Progenitor Cells ◽

Cell Number ◽

Induced Pluripotent

Background Several pieces of evidence from in vitro studies showed that brain-derived neurotrophic factor (BDNF) promotes proliferation and differentiation of neural stem/progenitor cells (NSCs) into neurons. Moreover, the JAK2 pathway was proposed to be associated with mouse NSC proliferation. BDNF could activate the STAT-3 pathway and induce proliferation in mouse NSCs. However, its effects on proliferation are not fully understood and JAK/STAT pathway was proposed to play a role in this activity. Methods In the present study, the effects of BDNF on cell proliferation and neurite outgrowth of Alzheimer’s disease (AD) induced pluripotent stem cells (iPSCs)-derived human neural progenitor cells (hNPCs) were examined. Moreover, a specific signal transduction pathway important in cell proliferation was investigated using a JAK2 inhibitor (AG490) to clarify the role of that pathway. Results The proliferative effect of BDNF was remarkably observed as an increase in Ki-67 positive cells. The cell number of hNPCs was significantly increased after BDNF treatment represented by cellular metabolic activity of the cells measured by MTT assay. This noticeable effect was statistically shown at 20 ng/ml of BDNF treatment. BDNF, however, did not promote neurite outgrowth but increased neuronal cell number. It was found that AG490 suppressed hNPCs proliferation. However, this inhibitor partially decreased BDNF-induced hNPCs proliferation. These results demonstrated the potential role of BDNF for the amelioration of AD through the increase of AD-derived hNPCs number.

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