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Stem Cells Translational Medicine

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https://www.readbyqxmd.com/read/28337852/turning-potential-into-action-using-pluripotent-stem-cells-to-understand-heart-development-and-function-in-health-and-disease
#1
Hananeh Fonoudi, Alexis Bosman
Pluripotent stem cells hold enormous potential for regenerative therapies, however their ability to provide insight into early human development and the origins of disease could arguably provide an even greater outcome. This is primarily due to their contribution to the establishment of a powerful knowledge base of human development, something which all researchers and clinicians can potentially benefit from. Modeling human heart development and disease using pluripotent stem cells has already provided many important insights into cardiogenesis and cardiovascular disease mechanisms however, it is important to be aware of the complexities of this model system...
March 24, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28296268/feasibility-and-efficacy-of-intra-arterial-administration-of-mesenchymal-stem-cells-in-an-animal-model-of-double-toxin-induced-multiple-system-atrophy
#2
Ha Na Kim, Dong Yeol Kim, Se Hee Oh, Hyung Sook Kim, Kyung Suk Kim, Phil Hyu Lee
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of the central and autonomic nervous system. Because no drug treatment consistently benefits MSA patients, neuroprotective strategy using mesenchymal stem cells (MSCs) has a lot of concern for the management of MSA. In this study, we investigated the safety and efficacy of intra-arterial administration of MSCs via internal carotid artery (ICA) in an animal model of MSA. The study was composed of feasibility test using a ×10 and ×50 of a standard dose of MSCs (4 × 10(7) MSCs) and efficacy test using a ×0...
March 13, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28296283/effects-of-transendocardial-cd34-cell-transplantation-on-diastolic-parameters-in-patients-with-nonischemic-dilated-cardiomyopathy
#3
Mojca Bervar, Mirta Kozelj, Gregor Poglajen, Matjaz Sever, Gregor Zemljic, Sabina Frljak, Marko Cukjati, Peter Cernelc, François Haddad, Bojan Vrtovec
We sought to evaluate the physiological background and the effects of CD34(+) cell transplantation on diastolic parameters in nonischemic dilated cardiomyopathy patients (DCM). We enrolled 38 DCM patients with NYHA class III and LVEF <40% who underwent transendocardial CD34(+) cell transplantation. Peripheral blood CD34(+) cells were mobilized by G-CSF, collected via apheresis, and injected transendocardially in the areas of myocardial hibernation. Patients were followed for 1 year. At baseline, estimated filling pressures were significantly elevated (E/e'≥15) in 18 patients (Group A), and moderately elevated (E/e'<15) in 20 patients (Group B)...
March 11, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28296182/endothelial-progenitors-a-consensus-statement-on-nomenclature
#4
EDITORIAL
Reinhold J Medina, Chad L Barber, Florence Sabatier, Francoise Dignat-George, Juan M Melero-Martin, Kiarash Khosrotehrani, Osamu Ohneda, Anna M Randi, Jerry K Y Chan, Teruhide Yamaguchi, Victor W M Van Hinsbergh, Mervin C Yoder, Alan W Stitt
Endothelial progenitor cell (EPC) nomenclature remains ambiguous and there is a general lack of concordance in the stem cell field with many distinct cell subtypes continually grouped under the term "EPC." It would be highly advantageous to agree standards to confirm an endothelial progenitor phenotype and this should include detailed immunophenotyping, potency assays, and clear separation from hematopoietic angiogenic cells which are not endothelial progenitors. In this review, we seek to discourage the indiscriminate use of "EPCs," and instead propose precise terminology based on defining cellular phenotype and function...
March 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28276172/ascorbic-acid-promotes-the-stemness-of-corneal-epithelial-stem-progenitor-cells-and-accelerates-epithelial-wound-healing-in-the-cornea
#5
Jialin Chen, Jie Lan, Dongle Liu, Ludvig J Backman, Wei Zhang, Qingjun Zhou, Patrik Danielson
High concentration of ascorbic acid (vitamin C) has been found in corneal epithelium of various species. However, the specific functions and mechanisms of ascorbic acid in the repair of corneal epithelium are not clear. In this study, it was found that ascorbic acid accelerates corneal epithelial wound healing in vivo in mouse. In addition, ascorbic acid enhanced the stemness of cultured mouse corneal epithelial stem/progenitor cells (TKE2) in vitro, as shown by elevated clone formation ability and increased expression of stemness markers (especially p63 and SOX2)...
March 9, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28271621/first-characterization-of-human-amniotic-fluid-stem-cell-extracellular-vesicles-as-a-powerful-paracrine-tool-endowed-with-regenerative-potential
#6
Carolina Balbi, Martina Piccoli, Lucio Barile, Andrea Papait, Andrea Armirotti, Elisa Principi, Daniele Reverberi, Luisa Pascucci, Pamela Becherini, Luigi Varesio, Massimo Mogni, Domenico Coviello, Tiziano Bandiera, Michela Pozzobon, Ranieri Cancedda, Sveva Bollini
Human amniotic fluid stem cells (hAFS) have shown a distinct secretory profile and significant regenerative potential in several preclinical models of disease. Nevertheless, little is known about the detailed characterization of their secretome. Herein we show for the first time that hAFS actively release extracellular vesicles (EV) endowed with significant paracrine potential and regenerative effect. c-KIT(+) hAFS were isolated from leftover samples of amniotic fluid from prenatal screening and stimulated to enhance EV release (24 hours 20% O2 versus 1% O2 preconditioning)...
March 8, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28252842/effects-of-transendocardial-stem-cell-injection-on-ventricular-proarrhythmia-in-patients-with-ischemic-cardiomyopathy-results-from-the-poseidon-and-tac-hft-trials
#7
Archana Ramireddy, Chad R Brodt, Adam M Mendizabal, Darcy L DiFede, Chris Healy, Vishal Goyal, Yahya Alansari, James O Coffey, Juan F Viles-Gonzalez, Alan W Heldman, Jeffrey J Goldberger, Robert J Myerburg, Joshua M Hare, Raul D Mitrani
Transendocardial stem cell injection in patients with ischemic cardiomyopathy (ICM) improves left ventricular function and structure but has ill-defined effects on ventricular arrhythmias. We hypothesized that mesenchymal stem cell (MSC) implantation is not proarrhythmic. Post hoc analyses were performed on ambulatory ECGs collected from the POSEIDON and TAC-HFT trials. Eighty-eight subjects (mean age 61 ± 10 years) with ICM (mean EF 32.2% ± 9.8%) received treatment with MSC (n = 48), Placebo (n = 21), or bone marrow mononuclear cells (BMC) (n = 19)...
March 2, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28244269/selective-expansion-of-skeletal-muscle-stem-cells-from-bulk-muscle-cells-in-soft-three-dimensional-fibrin-gel
#8
Pei Zhu, Yalu Zhou, Furen Wu, Yuanfan Hong, Xin Wang, Gajendra Shekhawat, Jeffrey Mosenson, Wen-Shu Wu
Muscle stem cells (MuSCs) exhibit robust myogenic potential in vivo, thus providing a promising curative treatment for muscle disorders. Ex vivo expansion of adult MuSCs is highly desired to achieve a therapeutic cell dose because of their scarcity in limited muscle biopsies. Sorting of pure MuSCs is generally required for all the current culture systems. Here we developed a soft three-dimensional (3D) salmon fibrin gel culture system that can selectively expand mouse MuSCs from bulk skeletal muscle preparations without cell sorting and faithfully maintain their regenerative capacity in culture...
February 28, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28244243/angiotensin-ii-causes-apoptosis-of-adult-hippocampal-neural-stem-cells-and-memory-impairment-through-the-action-on-ampk-pgc1%C3%AE-signaling-in-heart-failure
#9
Min-Seok Kim, Geun-Hee Lee, Yong-Min Kim, Byoung-Wook Lee, Hae Yun Nam, U-Cheol Sim, Suk-Jung Choo, Seong-Woon Yu, Jae-Joong Kim, Yunhee Kim Kwon, Seong Who Kim
Data are limited on the mechanisms underlying memory impairment in heart failure (HF). We hypothesized that angiotensin II (Ang II) may determine the fate of adult hippocampal neural stem cells (HCNs), a cause of memory impairment in HF. HCNs with neurogenesis potential were isolated and cultured from adult rat hippocampi. Ang II decreased HCN proliferation in dose- and time-dependent manners. Moreover, Ang II treatment (1 µM) for 48 hours induced apoptotic death, which was attenuated by pretreatment with Ang II receptor blockers (ARBs)...
February 28, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28244236/concise-reviews-innate-and-adaptive-immune-recognition-of-allogeneic-and-xenogeneic-cell-transplants-in-the-central-nervous-system
#10
Chloé J Hoornaert, Debbie Le Blon, Alessandra Quarta, Jasmijn Daans, Herman Goossens, Zwi Berneman, Peter Ponsaerts
Over the last 30 years, numerous allogeneic and xenogeneic cell grafts have been transplanted into the central nervous system (CNS) of mice and men in an attempt to cure neurological diseases. In the early studies, human or porcine embryonic neural cells were grafted in the striatum of animals or patients in an attempt to replace lost neurons. Although the immune-privileged status of the brain as a recipient organ was widely accepted, it rapidly became evident that CNS-grafted allogeneic and xenogeneic cells could be recognized and rejected by the immune system, resulting in poor neural graft survival and limited functional recovery...
February 28, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28233474/induced-pluripotent-stem-cell-derived-endothelial-cells-overexpressing-interleukin-8-receptors-a-b-and-or-c-c-chemokine-receptors-2-5-inhibit-vascular-injury-response
#11
Samantha Giordano, Xiangmin Zhao, Yiu-Fai Chen, Silvio H Litovsky, Fadi G Hage, Tim M Townes, Chiao-Wang Sun, Li-Chen Wu, Suzanne Oparil, Dongqi Xing
Recruitment of neutrophils and monocytes/macrophages to the site of vascular injury is mediated by binding of chemoattractants to interleukin (IL) 8 receptors RA and RB (IL8RA/B) C-C chemokine receptors (CCR) 2 and 5 expressed on neutrophil and monocyte/macrophage membranes. Endothelial cells (ECs) derived from rat-induced pluripotent stem cells (RiPS) were transduced with adenovirus containing cDNA of IL8RA/B and/or CCR2/5. We hypothesized that RiPS-ECs overexpressing IL8RA/B (RiPS-IL8RA/B-ECs), CCR2/5 (RiPS-CCR2/5-ECs), or both receptors (RiPS-IL8RA/B+CCR2/5-ECs) will inhibit inflammatory responses and neointima formation in balloon-injured rat carotid artery...
February 24, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28225193/human-neural-progenitor-transplantation-rescues-behavior-and-reduces-%C3%AE-synuclein-in-a-transgenic-model-of-dementia-with-lewy-bodies
#12
Natalie R S Goldberg, Samuel E Marsh, Joseph Ochaba, Brandon C Shelley, Hayk Davtyan, Leslie M Thompson, Joan S Steffan, Clive N Svendsen, Mathew Blurton-Jones
Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α-synuclein (α-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB...
February 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28224719/cardiomyocyte-differentiation-promotes-cell-survival-during-nicotinamide-phosphoribosyltransferase-inhibition-through-increased-maintenance-of-cellular-energy-stores
#13
Erin M Kropp, Katarzyna A Broniowska, Matthew Waas, Alyssa Nycz, John A Corbett, Rebekah L Gundry
To address concerns regarding the tumorigenic potential of undifferentiated human pluripotent stem cells (hPSC) that may remain after in vitro differentiation and ultimately limit the broad use of hPSC-derivatives for therapeutics, we recently described a method to selectively eliminate tumorigenic hPSC from their progeny by inhibiting nicotinamide phosphoribosyltransferase (NAMPT). Limited exposure to NAMPT inhibitors selectively removes hPSC from hPSC-derived cardiomyocytes (hPSC-CM) and spares a wide range of differentiated cell types; yet, it remains unclear when and how cells acquire resistance to NAMPT inhibition during differentiation...
February 22, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213979/mmp-2-and-mmp-14-silencing-inhibits-vegfr2-cleavage-and-induces-the-differentiation-of-porcine-adipose-derived-mesenchymal-stem-cells-to-endothelial-cells
#14
Sami G Almalki, Yovani Llamas Valle, Devendra K Agrawal
The molecular mechanisms that control the ability of adipose-derived mesenchymal stem cells (AMSCs) to remodel three-dimensional extracellular matrix barriers during differentiation are not clearly understood. Herein, we studied the expression of matrix metalloproteinases (MMPs) during the differentiation of AMSCs to endothelial cells (ECs) in vitro. MSCs were isolated from porcine abdominal adipose tissue, and characterized by immunopositivity to CD44, CD90, CD105, and immunonegativity to CD14 and CD45. Plasticity of AMSCs was confirmed by multilineage differentiation...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213976/enhancement-of-%C3%AE-globin-gene-expression-in-thalassemic-ivs2-654-induced-pluripotent-stem-cell-derived-erythroid-cells-by-modified-u7-snrna
#15
Phetcharat Phanthong, Suparerk Borwornpinyo, Narisorn Kitiyanant, Natee Jearawiriyapaisarn, Lalana Nuntakarn, Jirawat Saetan, Tiwaporn Nualkaew, Khanit Sa-Ngiamsuntorn, Usanarat Anurathapan, Andras Dinnyes, Yindee Kitiyanant, Suradej Hongeng
The therapeutic use of patient-specific induced pluripotent stem cells (iPSCs) is emerging as a potential treatment of β-thalassemia. Ideally, patient-specific iPSCs would be genetically corrected by various approaches to treat β-thalassemia including lentiviral gene transfer, lentivirus-delivered shRNA, and gene editing. These corrected iPSCs would be subsequently differentiated into hematopoietic stem cells and transplanted back into the same patient. In this article, we present a proof of principle study for disease modeling and screening using iPSCs to test the potential use of the modified U7 small nuclear (sn) RNA to correct a splice defect in IVS2-654 β-thalassemia...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213970/efficacy-and-safety-of-immuno-magnetically-sorted-smooth-muscle-progenitor-cells-derived-from-human-induced-pluripotent-stem-cells-for-restoring-urethral-sphincter-function
#16
Yanhui Li, Morgaine Green, Yan Wen, Yi Wei, Prachi Wani, Zhe Wang, Renee Reijo Pera, Bertha Chen
Human-induced pluripotent stem cells (hiPSCs)-based cell therapy holds promise for treating stress urinary incontinence (SUI). However, safety concerns, especially tumorgenic potential of residual undifferentiated cells in hiPSC derivatives, are major barriers for its clinical translation. An efficient, fast and clinical-scale strategy for purifying committed cells is also required. Our previous studies demonstrated the regenerative effects of hiPSC-derived smooth muscle progenitor cells (pSMCs) on the injured urethral sphincter in SUI, but the differentiation protocol required fluorescence-activated cell sorting (FACS) which is not practical for autologous clinical applications...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213969/highly-efficient-neural-conversion-of-human-pluripotent-stem-cells-in-adherent-and-animal-free-conditions
#17
Dunja Lukovic, Andrea Diez Lloret, Petra Stojkovic, Daniel Rodríguez-Martínez, Maria Amparo Perez Arago, Francisco Javier Rodriguez-Jimenez, Patricia González-Rodríguez, José López-Barneo, Eva Sykova, Pavla Jendelova, Jelena Kostic, Victoria Moreno-Manzano, Miodrag Stojkovic, Shomi S Bhattacharya, Slaven Erceg
Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal-free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213967/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stem-cells-improve-survival-from-lethal-hepatic-failure-in-mice
#18
Hiroaki Haga, Irene K Yan, Kenji Takahashi, Akiko Matsuda, Tushar Patel
Stem cell-based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. Therapeutic effects of bone-marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d-galactosamine/tumor necrosis factor-α (TNF-α)...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205428/systemically-infused-mesenchymal-stem-cells-show-different-homing-profiles-in-healthy-and-tumor-mouse-models
#19
Chengying Xie, Zhangru Yang, Yuanzhen Suo, Qianqian Chen, Dan Wei, Xiaofu Weng, Zhengqin Gu, Xunbin Wei
Bone marrow-derived mesenchymal stem cells (MSCs) can localize in injured, inflamed, and cancerous tissues after systemic infusion. However, the dynamic homing profile of MSCs in the peripheral blood is not well characterized. Here, using in vivo flow cytometry to noninvasively monitor the dynamics of fluorescence-labeled cells, we found different clearance kinetics of systemically infused MSCs between healthy and tumor mouse models. The circulation times of MSCs in healthy mice and mice with subcutaneous tumors, orthotopically transplanted liver tumors, or metastatic lung tumors were 30, 24, 18, and 12 hours, respectively, suggesting that MSCs actively home to tumor environments...
February 16, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28205415/microfluidic-screening-reveals-heparan-sulfate-enhances-human-mesenchymal-stem-cell-growth-by-modulating-fibroblast-growth-factor-2-transport
#20
Drew M Titmarsh, Clarissa L L Tan, Nick R Glass, Victor Nurcombe, Justin J Cooper-White, Simon M Cool
Cost-effective expansion of human mesenchymal stem/stromal cells (hMSCs) remains a key challenge for their widespread clinical deployment. Fibroblast growth factor-2 (FGF-2) is a key hMSC mitogen often supplemented to increase hMSC growth rates. However, hMSCs also produce endogenous FGF-2, which critically interacts with cell surface heparan sulfate (HS). We assessed the interplay of FGF-2 with a heparan sulfate variant (HS8) engineered to bind FGF-2 and potentiate its activity. Bone marrow-derived hMSCs were screened in perfused microbioreactor arrays (MBAs), showing that HS8 (50 μg/ml) increased hMSC proliferation and cell number after 3 days, with an effect equivalent to FGF-2 (50 ng/ml)...
February 16, 2017: Stem Cells Translational Medicine
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