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https://www.readbyqxmd.com/read/28341222/the-science-and-ethics-of-cell-based-therapies-for-parkinson-s-disease
#1
REVIEW
C R Towns
Parkinson's Disease (PD) is an age-related, disabling neurodegenerative disorder. Although sufferers usually respond to dopamine agonists for extended periods, the disease remains progressive and adverse drug effects can compromise effective long term treatment. Cell-based therapies have been the subject of much hype and optimism with regard to PD. Proof of principle was provided in the 1980s with fetal tissue transplantation trials demonstrating successful graft survival. Embryonic stem cells and reprogrammed or transdifferentiated somatic cells may provide alternative sources of tissue with the potential to overcome the material shortages and technical difficulties that have hindered fetal neural transplants...
January 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#2
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28332620/novel-model-of-tendon-regeneration-reveals-distinct-cell-mechanisms-underlying-regenerative-and-fibrotic-tendon-healing
#3
Kristen Howell, Chun Chien, Rebecca Bell, Damien Laudier, Sara F Tufa, Douglas R Keene, Nelly Andarawis-Puri, Alice H Huang
To date, the cell and molecular mechanisms regulating tendon healing are poorly understood. Here, we establish a novel model of tendon regeneration using neonatal mice and show that neonates heal via formation of a 'neo-tendon' that differentiates along the tendon specific lineage with functional restoration of gait and mechanical properties. In contrast, adults heal via fibrovascular scar, aberrant differentiation toward cartilage and bone, with persistently impaired function. Lineage tracing identified intrinsic recruitment of Scx-lineage cells as a key cellular mechanism of neonatal healing that is absent in adults...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326305/implications-for-a-stem-cell-regenerative-medicine-based-approach-to-human-intervertebral-disk-degeneration
#4
REVIEW
Petra Kraus, Thomas Lufkin
The human body develops from a single cell, the zygote, the product of the maternal oocyte and the paternal spermatozoon. That 1-cell zygote embryo will divide and eventually grow into an adult human which is comprised of ~3.7 × 10(13) cells. The tens of trillions of cells in the adult human can be classified into approximately 200 different highly specialized cell types that make up all of the different tissues and organs of the human body. Regenerative medicine aims to replace or restore dysfunctional cells, tissues and organs with fully functional ones...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28323930/%C3%AE-cells-persist-in-t1d-pancreata-without-evidence-for-ongoing-%C3%AE-cell-turnover-or-neogenesis
#5
Carol J Lam, Daniel R Jacobson, Matthew M Rankin, Aaron R Cox, Jake A Kushner
Context: The cellular basis of persistent β-cell function in T1D remains enigmatic. No extensive quantitative β-cell studies of T1D pancreata have been performed to test for ongoing β-cell regeneration or neogenesis. Objective: We sought to determine the mechanism of β-cell persistence in T1D pancreata. Design: We studied T1D (n=47) and non-diabetic control (n=59) pancreata over a wide range of ages from the JDRF Network of Pancreatic Organ donors with Diabetes (nPOD) via high throughput microscopy...
February 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28299650/the-role-of-runx1-in-embryonic-blood-cell-formation
#6
Amanda D Yzaguirre, Marella F T R de Bruijn, Nancy A Speck
The de novo generation of hematopoietic stem and progenitor cells (HSPC) occurs solely during embryogenesis from a population of epithelial cells called hemogenic endothelium (HE). During midgestation HE cells in multiple intra- and extraembryonic vascular beds leave the vessel wall as they transition into HSPCs in a process termed the endothelial to hematopoietic transition (EHT). Runx1 expression in HE cells orchestrates the transcriptional switch necessary for the transdifferentiation of endothelial cells into functional HSPCs...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28290453/suppressive-il-17a-foxp3-and-ex-th17-il-17a-neg-foxp3-treg-cells-are-a-source-of-tumour-associated-treg-cells
#7
Stephanie Downs-Canner, Sara Berkey, Greg M Delgoffe, Robert P Edwards, Tyler Curiel, Kunle Odunsi, David L Bartlett, Nataša Obermajer
Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17-Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3(+) cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive IL-17A(+)Foxp3(+) and ex-Th17 Foxp3(+) cells are converted from IL-17A(+)Foxp3(neg) cells in tumour-bearing mice. Metabolic phenotyping of Foxp3-expressing IL-17A(+), ex-Th17 and iTreg cells demonstrates the dissociation between the metabolic fitness and the suppressive function of Foxp3-expressing Treg cell subsets...
March 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28286110/fast-transdifferentiation-of-human-wharton-s-jelly-mesenchymal-stem-cells-into-neurospheres-and-nerve-like-cells
#8
A R Bonilla-Porras, C Velez-Pardo, M Jimenez-Del-Rio
BACKGROUND: The human mesenchymal stem cells derived from Wharton's jelly tissue (hWJ-MSCs) represent a tool for cell-based therapies and regenerative medicine. hWJ-MSCs form neurospheres (NSs) within 3-7 days. No data is available to establish the neuro-phenotypic markers and time of formation of nerve-like (NLCs) and glial cells from NSs derived from hWJ-MSCs. NEW METHOD: hWJ-MSCs were incubated with Fast-N-Spheres medium for 24 and 72h. The new formed NSs were in turn incubated with forskolin in neurogenic NeuroForsk medium for 1-7days...
March 8, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28284719/hypoxia-mediated-mechanisms-associated-with-antiangiogenic-treatment-resistance-in-glioblastomas
#9
REVIEW
Sean Mahase, Rachel N Rattenni, Pieter Wesseling, William Leenders, Clarissa Baldotto, Rajan Jain, David Zagzag
Glioblastomas (GBMs) are malignant tumors characterized by their vascularity and invasive capabilities. Antiangiogenic therapy (AAT) is a treatment option that targets GBM-associated vasculature to mitigate the growth of GBMs. However, AAT demonstrates transient effects, because many patients eventually develop resistance to this treatment. Several recent studies attempt to explain the molecular and biochemical basis of resistance to AAT in GBM patients. Experimental investigations suggest that the induction of extensive intratumoral hypoxia plays a key role in GBM escape from AAT...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28284717/evidence-mechanism-and-clinical-relevance-of-the-transdifferentiation-from-lung-adenocarcinoma-to-squamous-cell-carcinoma
#10
REVIEW
Shenda Hou, Shiyu Zhou, Zhen Qin, Liu Yang, Xiangkun Han, Shun Yao, Hongbin Ji
Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct subtypes of non-small-cell lung carcinoma. Interestingly, approximately 4% to 9% of human non-small-cell lung carcinoma tumors contain mixed adenomatous and squamous pathologies in a single lesion, clinically termed adenosquamous cell carcinoma. More important, these two different pathological components frequently share identical oncogenic mutations, indicative of a potential transition. Indeed, recent data have provided convincing evidence in supporting the ADC to SCC transdifferentiation in lungs...
March 8, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28283336/tissue-engineering-with-peripheral-blood-derived-mesenchymal-stem-cells-promotes-the-regeneration-of-injured-peripheral-nerves
#11
Mengjie Pan, Xianghai Wang, Yijing Chen, Shangtao Cao, Jinkun Wen, Guofeng Wu, Yuanyuan Li, Lixia Li, Changhui Qian, Zhenqi Qin, Zhenlin Li, Dandan Tan, Zhihao Fan, Wutian Wu, Jiasong Guo
Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP...
March 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28279194/crispr-targeted-genome-editing-of-mesenchymal-stem-cell-derived-therapies-for-type-1-diabetes-a-path-to-clinical-success
#12
REVIEW
Dario Gerace, Rosetta Martiniello-Wilks, Najah Therese Nassif, Sara Lal, Raymond Steptoe, Ann Margaret Simpson
Due to their ease of isolation, differentiation capabilities, and immunomodulatory properties, the therapeutic potential of mesenchymal stem cells (MSCs) has been assessed in numerous pre-clinical and clinical settings. Currently, whole pancreas or islet transplantation is the only cure for people with type 1 diabetes (T1D) and, due to the autoimmune nature of the disease, MSCs have been utilised either natively or transdifferentiated into insulin-producing cells (IPCs) as an alternative treatment. However, the initial success in pre-clinical animal models has not translated into successful clinical outcomes...
March 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28277007/microrna-mediated-non-viral-direct-conversion-of-embryonic-fibroblasts-to-cardiomyocytes-comparison-of-commercial-and-synthetic-non-viral-vectors
#13
Hyosuk Kim, Dongkyu Kim, Sook Hee Ku, Kwangmeyung Kim, Sun Hwa Kim, Ick Chan Kwon
Technological advances opened up new ways of directing cell fate conversion from one cell lineage to another. The direct cell conversion technique has recently attracted much attention in regenerative medicine to treat devastated organs and tissues, particularly having limited regenerative capacity such as the heart and brain. Unfortunately, its clinical application is severely limited due to a safety concern and immunogenicity of viral vectors, as human gene therapy did in the beginning stages. In this study, we examined the possibility of adopting non-viral vectors to direct cell conversion from mouse embryonic fibroblasts to induced cardiomyocytes (iCM) by transient transfection of four types of chemically synthesized micro-RNA mimics (miRNA-1, 133, 208, and 499)...
February 16, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28276156/retinoic-acid-inducible-gene-1-protein-rig1-like-receptor-pathway-is-required-for-efficient-nuclear-reprogramming
#14
Nazish Sayed, Frank Ospino, Farhan Himmati, Jieun Lee, Palas Chanda, Edward S Mocarski, John P Cooke
We have revealed a critical role for innate immune signaling in nuclear reprogramming to pluripotency, and in the nuclear reprogramming required for somatic cell transdifferentiation. Activation of innate immune signaling causes global changes in the expression and activity of epigenetic modifiers to promote epigenetic plasticity. In our previous papers, we focused on the role of toll-like receptor 3 (TLR3) in this signaling pathway. Here we define the role of another innate immunity pathway known to participate in the response to viral RNA, the retinoic acid-inducible gene 1 receptor (RIG-1)-like receptor (RLR) pathway...
March 9, 2017: Stem Cells
https://www.readbyqxmd.com/read/28274610/retinoic-acid-signaling-is-dispensable-for-somatic-development-and-function-in-the-mammalian-ovary
#15
Anna Minkina, Robin E Lindeman, Micah D Gearhart, Anne-Amandine Chassot, Marie-Christine Chaboissier, Norbert B Ghyselinck, Vivian J Bardwell, David Zarkower
Retinoic acid (RA) is a potent inducer of cell differentiation and plays an essential role in sex-specific germ cell development in the mammalian gonad. RA is essential for male gametogenesis and hence fertility. However, RA can also disrupt sexual cell fate in somatic cells of the testis, promoting transdifferentiation of male Sertoli cells to female granulosa-like cells when the male sexual regulator Dmrt1 is absent. The feminizing ability of RA in the Dmrt1 mutant somatic testis suggests that RA might normally play a role in somatic cell differentiation or cell fate maintenance in the ovary...
March 6, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28273952/comparative-analysis-of-lysyl-oxidase-like-family-members-in-pulmonary-fibrosis
#16
Verena Aumiller, Benjamin Strobel, Merrit Romeike, Michael Schuler, Birgit E Stierstorfer, Sebastian Kreuz
Extracellular matrix (ECM) composition and stiffness are major driving forces for the development and persistence of fibrotic diseases. Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. Here, we systematically investigated LOX/L expression in primary fibroblasts and epithelial cells under fibrotic conditions, Bleomycin (BLM) induced lung fibrosis and in human IPF tissue. Basal expression of all LOX/L family members was detected in epithelial cells and at higher levels in fibroblasts...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273314/losartan-attenuates-scar-formation-in-filtering-bleb-after-trabeculectomy
#17
Huimin Shi, Huiying Wang, Shuhao Fu, Kang Xu, Xiaoyan Zhang, Yiqin Xiao, Wen Ye
Purpose: To examine the effects of losartan on scar formation after trabeculectomy and on fibrotic changes of human Tenon's fibroblasts (HTFs). Methods: Trabeculectomy was performed on New Zealand rabbits. They were randomized to receive one of the following treatments: 0.9% normal saline, mitomycin-C, or one of the three doses of losartan. Bleb morphology, IOP, and histopathology examination were performed. Primary cultured HTFs were treated with losartan or vehicle, with or without angiotensin II (Ang II)...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28270694/acinar-cell-plasticity-and-development-of-pancreatic-ductal-adenocarcinoma
#18
REVIEW
Peter Storz
Acinar cells in the adult pancreas show high plasticity and can undergo transdifferentiation to a progenitor-like cell type with ductal characteristics. This process, termed acinar-to-ductal metaplasia (ADM), is an important feature facilitating pancreas regeneration after injury. Data from animal models show that cells that undergo ADM in response to oncogenic signalling are precursors for pancreatic intraepithelial neoplasia lesions, which can further progress to pancreatic ductal adenocarcinoma (PDAC). As human pancreatic adenocarcinoma is often diagnosed at a stage of metastatic disease, understanding the processes that lead to its initiation is important for the discovery of markers for early detection, as well as options that enable an early intervention...
March 8, 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28260136/cells-of-origin-of-pancreatic-neoplasms
#19
REVIEW
Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Tomoki Ebata, Masato Nagino
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignant disease associated with poor prognosis, despite recent medical advances. It is of great importance to understand the initial events and cells of origin of pancreatic cancer to prevent the development and progression of PDAC. There are three distinct precursor lesions that develop into PDAC: pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms (MCNs). Studies on genetically engineered mouse models have revealed that the initiation and development of these lesions largely depend on genetic alterations...
March 4, 2017: Surgery Today
https://www.readbyqxmd.com/read/28251714/the-transdifferentiation-of-regulatory-t-and-th17-cells-in-autoimmune-inflammatory-diseases-and-its-potential-implications-in-pregnancy-complications
#20
Zhao-Zhao Liu, Guo-Qiang Sun, Xiao-Hui Hu, Joanne Kwak-Kim, Ai-Hua Liao
In the past decades, studies have shown that a balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells plays a major role in autoimmune/inflammatory diseases as well as pregnancy complications. Decreased number and function of Tregs, and increased number of Th17 cells which often have an opposed effect of Tregs, are associated with these conditions. Recently, the plasticity of Tregs and Th17 cells has been reported to be involved in the pathogenesis of autoimmune/inflammatory diseases. Hence, we summarize the current knowledge of Tregs and Th17 cells plasticity with an emphasis on their reciprocal transdifferentiation in autoimmune/inflammatory diseases...
March 2, 2017: American Journal of Reproductive Immunology: AJRI
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