scholarly journals Noggin inactivation affects the number and differentiation potential of muscle progenitor cells in vivo

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Domiziana Costamagna ◽  
Hendrik Mommaerts ◽  
Maurilio Sampaolesi ◽  
Przemko Tylzanowski
Keyword(s):  
Progenitor Cells ◽  
Differentiation Potential ◽  
Muscle Progenitor Cells

scholarly journals Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration

2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Dong Joon Lee ◽  
Yonsil Park ◽  
Wei-Shou Hu ◽  
Ching-Chang Ko
Keyword(s):  
Bone Regeneration ◽  
Progenitor Cells ◽  
Adult Stem Cells ◽  
Single Cells ◽  
Osteogenic Potential ◽  
Type I ◽  
Differentiation Potential ◽  
Multipotent Adult Progenitor Cells

Osteogenic cells derived from rat multipotent adult progenitor cells (rMAPCs) were investigated for their potential use in bone regeneration. rMAPCs are adult stem cells derived from bone marrow that have a high proliferation capacity and the differentiation potential to multiple lineages. They may also offer immunomodulatory properties favorable for applications for regenerative medicine. rMAPCs were cultivated as single cells or as 3D aggregates in osteogenic media for up to 38 days, and their differentiation to bone lineage was then assessed by immunostaining of osteocalcin and collagen type I and by mineralization assays. The capability of rMAPCs in facilitating bone regeneration was evaluatedin vivoby the direct implantation of multipotent adult progenitor cell (MAPC) aggregates in rat calvarial defects. Bone regeneration was examined radiographically, histologically, and histomorphometrically. Results showed that rMAPCs successfully differentiated into osteogenic lineage by demonstrating mineralized extracellular matrix formationin vitroand induced new bone formation by the effect of rMAPC aggregatesin vivo. These outcomes confirm that rMAPCs have a good osteogenic potential and provide insights into rMAPCs as a novel adult stem cell source for bone regeneration.

scholarly journals Single cell dynamics of embryonic muscle progenitor cells in zebrafish

2018 ◽  
Author(s):  
Priyanka Sharma ◽  
Tyler D. Ruel ◽  
Katrinka M. Kocha ◽  
Shan Liao ◽  
Peng Huang
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Muscle Injury ◽  
Muscle Growth ◽  
Clonal Analysis ◽  
Muscle Stem Cells ◽  
Injury Repair ◽  
Embryonic Muscle ◽  
Muscle Progenitor Cells

ABSTRACTMuscle stem cells hold a great therapeutic potential in regenerating damaged muscles. However, the in vivo behavior of muscle stem cells during muscle growth and regeneration is still poorly understood. Using zebrafish as a model, we describe the in vivo dynamics and function of dermomyotome cells, a population of embryonic muscle progenitor cells. Dermomyotome cells are located in a superficial layer external to muscle fibers and express many extracellular matrix (ECM) genes including col1a2. Utilizing a new col1a2 transgenic line, we show that dermomyotome cells display a ramified morphology with dynamic cellular processes. Cell lineage tracing demonstrates that col1a2+ dermomyotome cells contribute to normal muscle growth as well as muscle injury repair. Combination of live imaging and single cell clonal analysis reveals a highly-choreographed process of muscle regeneration. Activated dermomyotome cells change from the quiescent ramified morphology to a polarized and elongated morphology and generate daughter cells that fuse with existing muscle fibers. Ablation of the dermomyotome severely compromises muscle injury repair. Our work provides a dynamic view of embryonic muscle progenitor cells during zebrafish muscle regeneration.Summary statementLive imaging and single cell clonal analysis reveal dynamic behaviors of zebrafish embryonic muscle progenitor cells in quiescence and activation.

Human Vascular Progenitor Cells Can Guide Mesodermal Lineage Choice of Mesenchymal Stem and Progenitor Cells After Co-Transplantation In Vivo.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 939-939
Author(s):  
Andreas Reinisch ◽  
Nathalie Etchart ◽  
Nicole A Hofmann ◽  
Anna Ortner ◽  
Eva Rohde ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Time Course ◽  
Conflicts Of Interest ◽  
Differentiation Potential ◽  
Environmental Conditioning ◽  
Non Invasive ◽  
Developmental Fate ◽  
Stem And Progenitor Cells ◽  
Proliferation Potential

Abstract Abstract 939 Background: Multilineage differentiation potential of mesenchymal stem and progenitor cells (MSPCs) make them attractive candidates for tissue regeneration purposes. Guiding the differentiation of MSPCs towards single lineages would facilitate their application for targeted therapies in vivo. We have previously shown that MSPCs are essential for endothelial colony-forming progenitor cell (ECFC)-derived patent vessel formation in vivo*[Blood 2009; 113 (26):6716-25]. Preliminary data indicate that the ratio of co-applied cells can change mesenchymal lineage differentiation from vascular support towards either osteogenesis with subsequent bone marrow (BM) ingrowth or chondrogenesis. We hypothesized that environmental conditioning by ECFCs plays an instructive role during the developmental fate decision of MSPCs in vivo. Methods: MSPCs as well as ECFCs were isolated from adult BM, white adipose tissue (WAT), umbilical cord blood (UCB) and perivascular cord tissue**[J Vis Exp. 2009;(32) pii: 1525]. Proliferation potential and clonogenicity were monitored. Phenotype was analyzed by flow cytometry and immune cytochemistry. Cell function was studied in differentiation assays and during vascular network assembly in vitro. Models for in vivo human vessel as compared to bone, BM or cartilage formation were established in immune-deficient NSG mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ). Non-invasive imaging was performed using computed tomography (CT), magnetic resonance (MRI) and near-infrared fluorescence imaging to elucidate the time course of heterotopic tissue development. Immune histochemistry was applied for morphologic studies of organogenesis. Results: Baseline analysis confirmed MSPC and ECFC purity, immune phenotype and sustained proliferation potential. We could show that human BM-derived MSPCs are capable of forming bone in vivo. Osteogenic differentiation and heterotopic ossicle formation was followed by attraction of mouse hematopoiesis and the establishment of entire murine BM including red and white blood cells and megakaryocytes within a human endosteal niche. Co-transplanted human ECFCs could instruct the MSPCs to differentiate also into pericytes or chondrocytes in vivo, depending on the applied MSPC/ECFC cell ratio. Non-invasive imaging and histological staining revealed that ectopic organogenesis had already started after 2–4 weeks and was stable during the observation period of 20 weeks. Non-BM-derived populations, although phenotypically identical, invariably lacked the capacity to build bone and marrow environment in this model in vivo. Conclusion: These data indicate that human ECFCs can instruct MSPCs and induce developmental fate decisions early in the time course of organ regeneration after transplantation. We suppose that effective regenerative stem cell therapy in vivo requires more than the injection of one single cell population. For vascular repair as compared to bone and marrow environment reconstitution our model is a promising tool to study the therapeutic applicability and risk profile of such ECFC/MSPC-based transplantation strategies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells

Blood ◽  
2006 ◽  
Vol 107 (10) ◽  
pp. 4182-4188 ◽  
Author(s):  
Jakub Tolar ◽  
Matthew J. O'Shaughnessy ◽  
Angela Panoskaltsis-Mortari ◽  
Ron T. McElmurry ◽  
Scott Bell ◽  
...  
Keyword(s):  
B Cell ◽  
Progenitor Cells ◽  
Nk Cell ◽  
Immunohistochemical Analysis ◽  
Differentiation Potential ◽  
Multipotent Adult Progenitor Cells ◽  
Deficient Mice

Multipotent adult progenitor cells (MAPCs) are marrow-derived pluripotent stem cells with a broad differentiation potential. We sought to identify factors that affect adoptively transferred MAPCs. In vitro, MAPCs expressed low levels of major histocompatibility complex (MHC) antigens, failed to stimulate CD4+ and CD8+ T-cell alloresponses, and were targets of NK cytolysis. To study in vivo biodistribution, we labeled MAPCs with luciferase for sequential quantification of bioluminescence and DsRed2 for immunohistochemical analysis. C57BL /6 MAPCs were infused intravenously into C57BL /6, Rag-2–/– (T- and B-cell–deficient), and Rag-2–/–/IL-2Rγc–/– (T-, B-, and NK-cell–deficient) mice. In C57BL /6 mice, MAPCs were transiently detected only in the chest compared with long-term persistence in T- and B-cell–deficient mice. NK depletion reduced MAPC elimination. Because the lungs were the major uptake site after intravenous injection, intra-arterial injections were tested and found to result in more widespread biodistribution. Widespread MAPC biodistribution and long-term persistence were seen in irradiated recipients given allogeneic marrow and MAPCs; such MAPCs expressed MHC class I antigens in tissues. Our data indicate that the biodistribution and persistence of reporter gene–labeled MAPCs are maximized after intra-arterial delivery or host irradiation and that T cells, B cells, and NK cells contribute to in vivo MAPC rejection.

Abstract 16189: Lineage Tracing of Postnatal Cardiomyogenic Progenitor Cells

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuan-Hung Liu ◽  
Shih-Yun Huang ◽  
Yi-Shuan Lin ◽  
Hsing-Yu Huang
Keyword(s):  
Progenitor Cells ◽  
Heart Development ◽  
Lineage Tracing ◽  
Mouse Heart ◽  
Differentiation Potential ◽  
Genetic Ablation ◽  
Epicardial Cells ◽  
Cardiomyogenic Differentiation

Recent studies report that postnatal mammalian hearts undergo cardiomyocyte refreshment. While the exact origin of the cells involved in postnatal cardiomyogenesis remains unclear. Here, we identified a pool of Nkx2.5 enhancer expressing cells in the postnatal mouse heart with cardiomyogenic differentiation potential in vitro. We tracked the expression of a cardiac-specific enhancer of Nkx2.5 using inducible Nkx2.5 enhancer-Cre mice from embryonic development to adulthood and post-myocardial infarction (MI) and documented the Nkx2.5 enhancer expressing cells directly contribute to postnatal cardiomyogenesis in vivo. Upon genetic ablation of these activated progenitors after myocardial injury, the cardiac function deteriorated. Transcriptomic analysis of Nkx2.5 enhancer expressing cells showed high expression of heart development genes. To trace the developmental origin of the activated Nkx2.5 cardiomyogenic progenitor cells, we created different lineage-Cre/Nkx2.5 enh-eGFP/ROSA26 reporter triple transgenic mice. Post-MI Nkx2.5 cardiomyogenic progenitor cells originated from the embryonic epicardial cells, not from the pre-existing cardiomyocytes, endothelial cells, cardiac neural crest cells, or perinatal/postnatal epicardial cells. Together, this study confirmed that cardiac lineage-specific progenitor cells, which originate from embryonic epicardium-derived cells, contribute to postnatal mammalian cardiomyogenesis.

scholarly journals Integrin Profile and In Vivo Homing of Human Smooth Muscle Progenitor Cells

Circulation ◽  
2004 ◽  
Vol 110 (17) ◽  
pp. 2673-2677 ◽  
Author(s):  
Arjun Deb ◽  
Kimberly A. Skelding ◽  
Shaohua Wang ◽  
Margo Reeder ◽  
David Simper ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Progenitor Cells ◽  
Muscle Progenitor Cells

In vivo differentiation potential of tracheal basal cells: evidence for multipotent and unipotent subpopulations

2004 ◽  
Vol 286 (4) ◽  
pp. L643-L649 ◽  
Author(s):  
Kyung U. Hong ◽  
Susan D. Reynolds ◽  
Simon Watkins ◽  
Elaine Fuchs ◽  
Barry R. Stripp
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Tracheal Epithelium ◽  
Secretory Cells ◽  
Basal Cells ◽  
Cell Type ◽  
Cell Hyperplasia ◽  
Differentiation Potential ◽  
Airway Injury

The composition of the conducting airway epithelium varies significantly along the proximal to distal axis, with that of the tracheal epithelium exhibiting the greatest complexity. A number of progenitor cells have been proposed to contribute to the maintenance of this cellular diversity both in the steady state and in response to injury. However, individual roles for each progenitor cell type are poorly defined in vivo. The present study was undertaken to investigate the hypothesis that basal cells represent a multipotent progenitor cell type for renewal of the injured tracheal epithelium. To understand their contribution to epithelial repair, mice were exposed to naphthalene to induce airway injury and depletion of the secretory cell progenitor pool. Injury resulted in a rapid induction of cytokeratin 14 (K14) expression among the majority of GSI-B4-reactive cells and associated hyperplasia of basal cells. Restoration of depleted secretory cells occurred after 6 days of recovery and was associated with regression of the basal cell hyperplasia, suggesting a progenitor-progeny relationship. Multipotent differentiation of basal cells was confirmed using a bitransgenic ligand-regulated Cre-loxP reporter approach in which expression of a ubiquitously expressed LacZ reporter was activated within K14-expressing progenitor cells during airway repair. With the use of this approach, it was determined that K14-expressing cells include subsets capable of either multipotent or unipotent differentiation in vivo. We conclude that basal cells have the capacity for restoration of a fully differentiated epithelium.

Single-Cell Analysis of Lymphoid-Primed Multipotent Progenitors (LMPPs) Reveal Alterations in Lineage Commitment during Aging

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 244-244
Author(s):  
Sneha Borikar ◽  
Vivek Philip ◽  
Jennifer J. Trowbridge
Keyword(s):  
Single Cell ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Conflicts Of Interest ◽  
Single Cells ◽  
Differentiation Potential ◽  
Increased Risk

Abstract During aging, the hematopoietic compartment undergoes lineage skewing, biased toward myeloid differentiation at the expense of lymphoid differentiation. This skewing clinically presents as impaired adaptive immunity and an increased risk of myeloproliferative disorders. However, little is known of the regulatory mechanisms underlying these changes in differentiation potential due in part to the inadequacy of current analytic techniques to evaluate lineage potency of individual progenitor cells. Recent demonstration that long-lived hematopoietic progenitor cells drive steady-state hematopoiesis has shifted focus onto the progenitor cell compartment to understand clonal dynamics of native hematopoiesis. Here, we critically assess the functional and molecular alterations in the multipotent progenitor cell pool with aging at the single-cell level. We developed novel in vitro and in vivo assays to define the heterogeneity of the LMPP population and test cell-fate potential from single cells. Our results demonstrate, for the first time, distinct, intrinsic lineage potential of single in vitro LMPPs at the cellular and molecular level. We find that clonal alterations in the lymphoid-primed multipotent progenitor (LMPP) compartment contributes to the functional alterations in hematopoiesis observed during aging. Unbiased single-cell transcriptome analysis reveals that true multipotential clones and lymphoid-restricted clones are reduced with aging, while bipotential and myeloid-restricted clones are modestly expanded. Furthermore, myeloid-restricted clones gain myc driver signatures, molecularly identifying clones emerging during aging that are susceptible to transformation. Our study reveals that aging alters the clonal composition of multipotential progenitor cells, directly contributing to the global loss of the lymphoid compartment and increased susceptibility to myeloid transformation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pluripotent stem cell-induced skeletal muscle progenitor cells with givinostat promote myoangiogenesis and restore dystrophin in injured Duchenne dystrophic muscle

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wanling Xuan ◽  
Mahmood Khan ◽  
Muhammad Ashraf
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Inflammatory Cells ◽  
Dystrophic Muscle ◽  
Muscle Progenitor Cells ◽  
And Migration ◽  
Migration Capacity ◽  
Muscle Gene ◽  
Proliferation And Migration

Abstract Background Duchenne muscular dystrophy (DMD) is caused by mutations of the gene that encodes the protein dystrophin. A loss of dystrophin leads to severe and progressive muscle wasting in both skeletal and heart muscles. Human induced pluripotent stem cells (hiPSCs) and their derivatives offer important opportunities to treat a number of diseases. Here, we investigated whether givinostat (Givi), a histone deacetylase inhibitor, with muscle differentiation properties could reprogram hiPSCs into muscle progenitor cells (MPC) for DMD treatment. Methods MPC were generated from hiPSCs by treatment with CHIR99021 and givinostat called Givi-MPC or with CHIR99021 and fibroblast growth factor as control-MPC. The proliferation and migration capacity were investigated by CCK-8, colony, and migration assays. Engraftment, pathological changes, and restoration of dystrophin were evaluated by in vivo transplantation of MPC. Conditioned medium from cultured MPC was collected and analyzed for extracellular vesicles (EVs). Results Givi-MPC exhibited superior proliferation and migration capacity compared to control-MPC. Givi-MPC produced less reactive oxygen species (ROS) after oxidative stress and insignificant expression of IL6 after TNF-α stimulation. Upon transplantation in cardiotoxin (CTX)-injured hind limb of Mdx/SCID mice, the Givi-MPC showed robust engraftment and restored dystrophin in the treated muscle than in those treated with control-MPC or human myoblasts. Givi-MPC significantly limited infiltration of inflammatory cells and reduced muscle necrosis and fibrosis. Additionally, Givi-MPC seeded the stem cell pool in the treated muscle. Moreover, EVs released from Givi-MPC were enriched in several miRNAs related to myoangiogenesis including miR-181a, miR-17, miR-210 and miR-107, and miR-19b compared with EVs from human myoblasts. Conclusions It is concluded that hiPSCs reprogrammed into MPC by givinostat possessing anti-oxidative, anti-inflammatory, and muscle gene-promoting properties effectively repaired injured muscle and restored dystrophin in the injured muscle.

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