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Stem Cells

Naohiro Uezono, Yicheng Zhu, Yusuke Fujimoto, Tetsuro Yasui, Taito Matsuda, Masahide Nakajo, Masahiko Abematsu, Takao Setoguchi, Shuji Mori, Hideo K Takahashi, Setsuro Komiya, Masahiro Nishibori, Kinichi Nakashima
Together with residual host neurons, transplanted neural stem cell (NSC)-derived neurons play a critical role in reconstructing disrupted neural circuits after spinal cord injury (SCI). Since a large number of tracts are disrupted and the majority of host neurons die around the lesion site as the damage spreads, minimizing this spreading and preserving the lesion site are important for attaining further improvements in reconstruction. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern protein that triggers sterile inflammation after tissue injury...
March 8, 2018: Stem Cells
Lozan Sheriff, Asma Alanazi, Lewis S C Ward, Carl Ward, Hafsa Munir, Julie Rayes, Mohammed Alassiri, Steve P Watson, Phil N Newsome, G Ed Rainger, Neena Kalia, Jon Frampton, Helen M McGettrick, Gerard B Nash
We investigated the adhesive behaviour of mesenchymal stem cells (MSC) in blood, which might influence their fate when infused as therapy. Isolated human bone marrow (BM) or umbilical cord (UC) MSC adhered efficiently from flow to the matrix proteins, collagen or fibronectin, but did not adhere to endothelial selectins. However, when suspended in blood, BMMSC no longer adhered to collagen, while UCMSC adhered along with many aggregated platelets. Neither MSC adhered to fibronectin from flowing blood, although the fibronectin surface did become coated with a platelet monolayer...
February 28, 2018: Stem Cells
Hyun-Jai Cho, Jin-Woo Lee, Hyun-Ju Cho, Choon-Soo Lee, Hyo-Soo Kim
The nature of calcifying progenitor cells remains elusive. In this study, we investigated the developmental hierarchy and dynamics of progenitor cells. In vitro and in vivo reconstitution assays demonstrated that Sca-1+/PDGFRα- cells in the bone marrow (BM) are the ancestors of Sca-1+/PDGFRα+ cells. Cells of CD29+Sca-1+/PDGFRα- lineage in the BM showed both hematopoietic potential with osteoclastic differentiation ability as well as mesenchymal stem cell-like properties with osteoblastic differentiation potential...
February 27, 2018: Stem Cells
Katherine G Akers, Yoan Chérasse, Yuki Fujita, Sakthivel Srinivasan, Takeshi Sakurai, Masanori Sakaguchi
Neural stem and progenitor cells continue to generate new neurons in particular regions of the brain during adulthood. One of these neurogenic regions is the dentate gyrus (DG) of the hippocampus, which plays an important role in cognition and emotion. By exploiting this innate neuronal regeneration mechanism in the DG, new technologies have the potential to promote resistance to or recovery from brain dysfunction or degeneration. However, a deeper understanding of how adult DG neurogenesis is regulated by factors such as sleep and epigenetic modifications of gene expression could lead to further breakthroughs in the clinical application of neural stem and progenitor cells...
February 27, 2018: Stem Cells
Sarah E J Chambers, Christina L O'Neill, Jasenka Guduric-Fuchs, Kiran J McLoughlin, Aaron Liew, Aoife M Egan, Timothy O'Brien, Alan W Stitt, Reinhold J Medina
Myeloid angiogenic cells (MACs) promote revascularization through the paracrine release of angiogenic factors and have been harnessed as therapeutic cells for many ischemic diseases. However, their proangiogenic properties have been suggested to be diminished in diabetes. This study investigates how the diabetic milieu affects the immunophenotype and function of MACs. Both MACs isolated from diabetic conditions and healthy cells exposed to a diabetic environment were used to determine the potential of MACs as a cell therapy for diabetic-related ischemia...
February 27, 2018: Stem Cells
Ling-Ping Cen, Tsz Kin Ng, Jia-Jian Liang, Xi Zhuang, Xiaowu Yao, Gary Hin-Fai Yam, Haoyu Chen, Herman S Cheung, Mingzhi Zhang, Chi Pui Pang
Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury...
February 24, 2018: Stem Cells
Stuart P Atkinson
No abstract text is available yet for this article.
February 21, 2018: Stem Cells
Deepak Bhere, Rajiv Kumar Khajuria, William T Hendriks, Antara Bandyopadhyay, Tugba Bagci-Onder, Khalid Shah
Stem cells are emerging as promising treatment strategies for several brain disorders and pathologies including brain tumors. In this study, we explored the potential of creating induced pluripotent stem cell (iPSC) derived therapeutic NSCs (ipNSC) by using either unmodified or gene-modified somatic cells and tested their fate and therapeutic efficacies in vitro and in vivo. We show that cells engineered in somatic state lose transgene-expression during the neural induction process, which is partially restored by HDAC inhibitor (i) treatment whereas cells engineered at the ipNSC state have sustained expression of transgenes...
February 16, 2018: Stem Cells
Yongfeng He, Erika Hooker, Eun-Jeong Yu, Huiqing Wu, Gerald R Cunha, Zijie Sun
Androgen signaling is essential for prostate development, morphogenesis, and regeneration. Emerging evidence indicates that Wnt/β-catenin signaling also contributes to prostate development specifically through regulation of cell fate determination. Prostatic Axin2-expressing cells are able to respond to Wnt signals and possess the progenitor properties to regenerate prostatic epithelium. Despite critical roles of both signaling pathways, the biological significance of androgen receptor (AR) in Axin2-expressing Wnt-responsive cells remains largely unexplored...
February 16, 2018: Stem Cells
Zhen Zheng, Li Zhang, Yi Qu, Guoguang Xiao, Shiping Li, Shan Bao, Q Richard Lu, Dezhi Mu
Hypoxic-ischemic encephalopathy (HIE) is a serious disease for neonates. However, present therapeutic strategies are not effective enough for treating HIE. Previous study showed that mesenchymal stem cells (MSCs) can exert neuroprotective effects for brain damage, but its mechanism remains elusive. Using in vitro coculture of rat cortical primary neurons and MSCs in HI conditions, we demonstrated that MSCs help increase brain derived neurotrophic factor (BDNF) and autophagy markers (LC3II and Beclin1) in the cultures and decrease cells death (lactate dehydrogenase levels)...
February 16, 2018: Stem Cells
Fei Li, Myles H Alderman, Aya Tal, Ramanaiah Mamillapalli, Alexis Coolidge, Demetra Hufnagel, Zhihao Wang, Elham Neisani, Stephanie Gidicsin, Graciela Krikun, Hugh S Taylor
Endometriosis is ectopic growth of endometrial tissue traditionally thought to arise through retrograde menstruation. We aimed to determine if cells derived from endometriosis could enter vascular circulation and lead to hematogenous dissemination. Experimental endometriosis was established by transplanting endometrial tissue from DsRed+ mice into the peritoneal cavity of DsRed- mice. Using flow cytometry, we identified DsRed+ cells in blood of animals with endometriosis. The circulating donor cells expressed CXCR4 and mesenchymal stem cell (MSC) biomarkers, but not hematopoietic stem cell markers...
February 16, 2018: Stem Cells
Said Assou, Julien Bouckenheimer, John De Vos
Human induced pluripotent stem cells (hiPSCs) have the potential to differentiate virtually into any cell type in unlimited quantities. Therefore, they are ideal for in vitro tissue modeling or to produce cells for clinical use. Importantly, and differently from immortalized and cancer cell lines, the hiPSC genome scrupulously reproduces that of the cell from which they were derived. However, hiPSCs can develop genetic abnormalities during reprogramming or prolonged cell culture, such as aneuploidies or oncogenic mutations (e...
February 14, 2018: Stem Cells
Collin Matsumoto, Yan Jiang, Jacqueline Emathinger, Pearl Quijada, Nathalie Nguyen, Andrea De La Torre, Maryam Moshref, Jonathan Nguyen, Aimee B Levinson, Minyoung Shin, Mark A Sussman, Nirmala Hariharan
Aging severely limits myocardial repair and regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesized that short telomeres activate p53 and induce autophagy to elicit the age-associated change in CPC fate. We isolated CPCs and compared mouse strains with different telomere lengths for phenotypic characteristics of aging. Wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres exhibits early cardiac aging with cardiac dysfunction, hypertrophy, fibrosis and senescence, as compared to common lab strains FVB and C57 bearing longer telomeres...
February 14, 2018: Stem Cells
Gustavo S Figueiredo, Borja Salvador-Culla, Oliver J Baylis, Hardeep S Mudhar, Majlinda Lako, Francisco C Figueiredo
PURPOSE: To investigate the outcomes of penetrating keratoplasty (PKP) following autologous cultivated limbal epithelial stem cell transplantation (CLET). METHODS: A prospective, single centre, interventional cohort study investigating patients with unilateral total limbal stem cell deficiency (LSCD) treated with CLET who underwent PKP. Patients with confirmed corneal re-epithelialization > 6 months post-CLET, and with best-corrected visual acuity (BCVA) <0...
February 13, 2018: Stem Cells
Trent Hall, Megan Walker, Miguel Ganuza, Per Holmfeldt, Marie Bordas, Guolian Kang, Wenjian Bi, Lance E Palmer, David Finkelstein, Shannon McKinney-Freeman
Hematopoietic stem and progenitor cells (HSPC) are necessary for life-long blood production and replenishment of the hematopoietic system during stress. We recently reported that nuclear factor I/X (Nfix) promotes HSPC survival post-transplant. Here, we report that ectopic expression of Nfix in primary mouse HSPCs extends their ex vivo culture from about 20 days to 40 days. HSPCs overexpressing Nfix display hypersensitivity to supportive cytokines and reduced apoptosis when subjected to cytokine deprivation relative to controls...
February 12, 2018: Stem Cells
Theresa Relation, Tai Yi, Adam J Guess, Krista La Perle, Satoru Otsuru, Suheyla Hasgur, Massimo Dominici, Christopher Breuer, Edwin M Horwitz
Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely utilized to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFNγ) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME)...
February 12, 2018: Stem Cells
Li-Tzu Wang, Shih-Sheng Jiang, Chiao-Hsuan Ting, Pei-Ju Hsu, Chia-Chi Chang, Huey-Kang Sytwu, Ko-Jiunn Liu, B Linju Yen
Multilineage tissue-source mesenchymal stem cells (MSCs) possess strong immunomodulatory properties and are excellent therapeutic agents, but require constant isolation from donors to combat replicative senescence. The differentiation of human induced pluripotent stem cells (iPSCs) into MSCs offers a renewable source of MSCs; however, reports on their immunomodulatory capacity have been discrepant. Using MSCs differentiated from iPSCs reprogrammed using diverse cell types and protocols, and in comparison to human embryonic stem cell (ESC)-MSCs and bone marrow (BM)-MSCs, we performed transcriptome analyses and assessed for functional immunomodulatory properties...
February 3, 2018: Stem Cells
Joseph Chen, Christian M Nefzger, Fernando J Rossello, Yu B Y Sun, Sue Mei Lim, Xiaodong Liu, Suzan de Boer, Anja S Knaupp, Jinhua Li, Kathryn C Davidson, Jose M Polo, Tiziano Barberi
The canonical Wnt/β-catenin pathway is crucial for early embryonic patterning, tissue homeostasis, and regeneration. While canonical Wnt/β-catenin stimulation has been used extensively to modulate pluripotency and differentiation of pluripotent stem cells (PSCs), the mechanism of these two seemingly opposing roles has not been fully characterized and is currently largely attributed to activation of nuclear Wnt target genes. Here, we show that low levels of Wnt stimulation via ectopic expression of Wnt1 or administration of glycogen synthase kinase-3 inhibitor CHIR99021 significantly increases PSC differentiation into neurons, cardiomyocytes and early endodermal intermediates...
February 2, 2018: Stem Cells
N Gupta, R Sinha, A Krasnodembskaya, X Xu, V Nizet, M A Matthay, J H Griffin
Bone marrow derived mesenchymal stromal cells (BM-MSCs) have been shown to have significant therapeutic effects in experimental models of pneumonia and lung injury. The current study examined the roles of the toll like receptor 4 (TLR4) and protease activated receptor 1 (PAR1) pathways on MSC survival and therapeutic activity in a murine model of pneumonia. MSCs from TLR4 -/- and R41Q-PAR1 mutated mice were isolated to test the effect of mutating these specific pathways on MSC survival when exposed to cytotoxic stimuli in vitro...
February 2, 2018: Stem Cells
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