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Bone marrow engraftment

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https://www.readbyqxmd.com/read/29231967/therapeutic-potential-of-porcine-bronchoalveolar-fluid-derived-mesenchymal-stromal-cells-in-a-pig-model-of-lps-induced-ali
#1
Mahesh Khatri, Levi Arthur Richardson
In this study, we isolated mesenchymal stromal (stem) cells (MSCs) from broncho-alveolar lavage fluid (BAL) of 2-6 week-old commercial pigs. BAL-MSCs displayed fibroblastic morphology and possessed self-renewal properties. Similar to bone-marrow MSCs, BAL-MSCs expressed mesenchymal markers and both cell types lacked the expression of hematopoetic markers. BAL-MSCs, when cultured in differentiation induction media, differentiated into adipocytes, osteocytes and chondrocytes. Next, we examined if BAL-MSCs have the ability to treat lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a pig model...
December 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29230885/intercellular-transfer-of-microvesicles-from-young-mesenchymal-stromal-cells-rejuvenates-aged-murine-hematopoietic-stem-cells
#2
Rohan Kulkarni, Manmohan Bajaj, Suprita Ghode, Sapana Jalnapurkar, Lalita Limaye, Vaijayanti Kale
Donor age is one of the major concerns in Bone Marrow Transplantation, as the aged hematopoietic stem cells (HSCs) fail to engraft efficiently. Here, using murine system we show that a brief interaction of aged HSCs with young mesenchymal stromal cells (MSCs) rejuvenates them and restores their functionality via inter-cellular transfer of microvesicles (MVs) containing autophagy-related mRNAs. Importantly, we show that MSCs gain activated AKT signaling as a function of aging. Activated AKT reduces the levels of autophagy-related mRNAs in their MVs, and partitions miR-17 and miR-34a into their exosomes, which upon transfer into HSCs down-regulate their autophagy-inducing mRNAs...
December 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/29229740/bone-marrow-derived-cpla2%C3%AE-contributes-to-renal-fibrosis-progression
#3
John R Montford, Allison M B Lehman, Colin D Bauer, Jelena Klawitter, Jost Klawitter, Joanna M Poczobutt, Micah Scobey, Mary Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson
The group IVA calcium dependent cytosolic phospholipase A2 enzyme (cPLA2α) directs a complex eicosanoid storm which accompanies the tissue response to injury. cPLA2α, and its downstream eicosanoid mediators, are also implicated in the pathogenesis of fibrosis in many organs including the kidney. We aimed to determine the role of cPLA2α in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). Wild type (WT) C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice (WT-BMT) or mice deficient in cPLA2α (KO-BMT)...
December 11, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29226242/intracerebroventricular-delivery-of-hematopoietic-progenitors-results-in-rapid-and-robust-engraftment-of-microglia-like-cells
#4
Alessia Capotondo, Rita Milazzo, Jose M Garcia-Manteiga, Eleonora Cavalca, Annita Montepeloso, Brian S Garrison, Marco Peviani, Derrick J Rossi, Alessandra Biffi
Recent evidence indicates that hematopoietic stem and progenitor cells (HSPCs) can serve as vehicles for therapeutic molecular delivery to the brain by contributing to the turnover of resident myeloid cell populations. However, such engraftment needs to be fast and efficient to exert its therapeutic potential for diseases affecting the central nervous system. Moreover, the nature of the cells reconstituted after transplantation and whether they could comprise bona fide microglia remain to be assessed. We demonstrate that transplantation of HSPCs in the cerebral lateral ventricles provides rapid engraftment of morphologically, antigenically, and transcriptionally dependable microglia-like cells...
December 2017: Science Advances
https://www.readbyqxmd.com/read/29217821/il-11-promotes-the-treatment-efficacy-of-hematopoietic-stem-cell-transplant-therapy-in-aplastic-anemia-model-mice-through-a-nf-%C3%AE%C2%BAb-microrna-204-thrombopoietin-regulatory-axis
#5
Yan Wang, Zhi-Yun Niu, Yu-Jie Guo, Li-Hua Wang, Feng-Ru Lin, Jing-Yu Zhang
Hematopoietic stem cell (HSC) transplantation could be of therapeutic value for aplastic anemia (AA) patients, and immunosuppressants may facilitate the efficiency of the procedure. As anti-inflammatory cytokine interleukin-11 (IL-11) has a thrombopoietic effect, its use in cases of chronic bone marrow failure, such as AA, has been proposed to induce HSC function. However, the putative mechanisms that may support this process remain poorly defined. We found that decreased miR-204-5p levels were coincident with increased proliferation in mouse HSCs following exposure to IL-11 in vitro...
December 8, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29215316/endothelial-progenitor-cells-for-cellular-angiogenesis-and-repair-lessons-learned-from-experimental-animal-models
#6
Khawaja Husnain Haider, Salim Aziz, Mateq Ali Al-Reshidi
Stem/progenitor cell-based therapy has been extensively studied for angiomyogenic repair of the ischemic heart by regeneration of the damaged myocytes and neovascularization of the ischemic tissue through biological bypassing. Given their inherent ability to assume functionally competent endothelial phenotype and release of broad array of proangiogenic cytokines, endothelial progenitor cells (EPCs)-based therapy is deemed as most appropriate for vaculogenesis in the ischemic heart. Emulating the natural repair process that encompasses mobilization and homing-in of the bone marrow and peripheral blood EPCs, their reparability has been extensively studied in the animal models of myocardial ischemia with encouraging results...
December 7, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/29214523/haematopoietic-stem-cell-transplantation-arrests-the-progression-of-neurodegenerative-disease-in-late-onset-tay-sachs-disease
#7
Karolina M Stepien, Su Han Lum, J Edmond Wraith, Christian J Hendriksz, Heather J Church, David Priestman, Frances M Platt, Simon Jones, Ana Jovanovic, Robert Wynn
Tay-Sachs disease is a rare metabolic disease caused by a deficiency of hexosaminidase A that leads to accumulation of GM2 gangliosides predominantly in neural tissue. Late-onset Tay-Sachs disease variant is associated with a higher level of residual HexA activity. Treatment options are limited, and there are a few described cases who have undergone haematopoietic stem cell transplantation (HSCT) with variable outcome.We describe a case of a 23-year-old male patient who presented with a long-standing tremor since 7 years of age...
December 7, 2017: JIMD Reports
https://www.readbyqxmd.com/read/29212046/hematopoietic-defects-in-response-to-reduced-arhgap21
#8
Juliana Xavier-Ferrucio, Lauremília Ricon, Karla Vieira, Ana Leda Longhini, Mariana Lazarini, Carolina Louzão Bigarella, Gilberto Franchi, Diane S Krause, Sara T O Saad
Arhgap21 is a member of the Rho GTPase activating protein (RhoGAP) family, which function as negative regulators of Rho GTPases. Arhgap21 has been implicated in adhesion and migration of cancer cells. However, the role of Arhgap21 has never been investigated in hematopoietic cells. Herein, we evaluated functional aspects of hematopoietic stem and progenitor cells (HSPC) using a haploinsufficient (Arhgap21+/-) mouse. Our results show that Arhgap21+/- mice have an increased frequency of phenotypic HSC, impaired ability to form progenitor colonies in vitro and decreased hematopoietic engraftment in vivo, along with a decrease in LSK cell frequency during serial bone marrow transplantation...
November 23, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29201599/combining-adoptive-treg-transfer-with-bone-marrow-transplantation-for-transplantation-tolerance
#9
REVIEW
Nina Pilat, Nicolas Granofszky, Thomas Wekerle
Purpose of Review: The mixed chimerism approach is an exceptionally potent strategy for the induction of donor-specific tolerance in organ transplantation and so far the only one that was demonstrated to work in the clinical setting. Regulatory T cells (Tregs) have been shown to improve chimerism induction in experimental animal models. This review summarizes the development of innovative BMT protocols using therapeutic Treg transfer for tolerance induction. Recent Findings: Treg cell therapy promotes BM engraftment in reduced conditioning protocols in both, mice and non-human primates...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29186350/macrophage-enzyme-and-reduced-inflammation-drive-brain-correction-of-mucopolysaccharidosis-iiib-by-stem-cell-gene-therapy
#10
Rebecca J Holley, Stuart M Ellison, Daniel Fil, Claire O'Leary, John McDermott, Nishanthi Senthivel, Alexander W W Langford-Smith, Fiona L Wilkinson, Zelpha D'Souza, Helen Parker, Aiyin Liao, Samuel Rowlston, Hélène F E Gleitz, Shih-Hsin Kan, Patricia I Dickson, Brian W Bigger
Mucopolysaccharidosis IIIB is a paediatric lysosomal storage disease caused by deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU), involved in the degradation of the glycosaminoglycan heparan sulphate. Absence of NAGLU leads to accumulation of partially degraded heparan sulphate within lysosomes and the extracellular matrix, giving rise to severe CNS degeneration with progressive cognitive impairment and behavioural problems. There are no therapies. Haematopoietic stem cell transplant shows great efficacy in the related disease mucopolysaccharidosis I, where donor-derived monocytes can transmigrate into the brain following bone marrow engraftment, secrete the missing enzyme and cross-correct neighbouring cells...
November 27, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29183989/left-or-right-directions-to-stem-cell-engraftment
#11
Mirjam E Belderbos, Leonid Bystrykh, Gerald de Haan
In this issue of JEM, Wu et al. (https://doi.org/10.1084/jem.20171341) use genetic barcoding of macaque hematopoietic stem cells to demonstrate that, after transplantation, HSCs are very asymmetrically distributed and uncover a thymus-independent pathway for mature T cell production in the bone marrow.
November 28, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29179600/nanovaccine-for-immunotherapy-and-reduced-hepatitis-b-virus-in-humanized-model
#12
Hitesh Kumar Dewangan, Tarun Pandey, Sanjay Singh
Chronic Hepatitis B Virus (HBV) infections are severe with weak antiviral immune responses. The lack of an appropriate small animal model for chronic hepatitis, a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B viral (HBV) infection. In this study, for enhancing the antibody production efficiency the prepared polymeric HBsAg-loaded nanoparticles (nanovaccine) will be tested in immune-deficit mice, which suffer from chronic Hepatitis B virus. Vaccination of Balb/c mice by this prepared nanoparticles that were engrafted with peripheral blood mononuclear cells (PBMCs), which was already lethally irradiated and transplanted by the bone marrow of NOD (knockout mice) mice...
November 27, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29175461/the-future-of-mesenchymal-stem-cell-based-therapeutic-approaches-for-cancer-from-cells-to-ghosts
#13
Andrea Mohr, Ralf Zwacka
Mesenchymal stem cells (MSCs) are multipotent stromal cells which can differentiate into a variety of cell types including osteoblasts, adipocytes and chondrocytes. They are normally resident in adipose tissue, bone marrow and the umbilical cord, but can also be found in other tissues and are known to be recruited to sites of wound healing as well as growing tumours. The therapeutic potential of MSCs has been explored in a number of phase I/II and III clinical trials, of which several were targeted against graft-versus-host disease and to support engraftment of haematopoietic stem cells (HSCs), but currently only very few in the oncology field...
November 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29168236/a-prospective-multicenter-phase-ii-study-of-intrabone-marrow-transplantation-of-unwashed-cord-blood-using-reduced-intensity-conditioning
#14
Masaya Okada, Taizo Tasaka, Kazuhiro Ikegame, Nobuyuki Aotsuka, Takeshi Kobayashi, Yuho Najima, Yoshiko Matsuhashi, Hideho Wada, Hirotoshi Tokunaga, Shinichi Masuda, Yoshikazu Utsu, Satoshi Yoshihara, Katsuji Kaida, Takashi Daimon, Hiroyasu Ogawa
Cord blood transplantation (CBT) is associated with delayed hematopoietic recovery and graft failure. To overcome these problems, we conducted a prospective, multicenter phase II study of intrabone marrow transplantation in which patients received reduced-intensity conditioning without anti-thymocyte globulin. The primary endpoint was the probability of full donor engraftment. Forty patients with hematologic malignancies were enrolled. CB cells were injected without washing into 4 iliac bone sites (2 at each hemipelvis), at which approximately 6 mL of CB was administered at one site with local anesthesia...
November 23, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29159905/autologous-mesenchymal-stem-cell-and-islet-cotransplantation-safety-and-efficacy
#15
Hongjun Wang, Charlie Strange, Paul J Nietert, Jingjing Wang, Taylor L Turnbull, Colleen Cloud, Stefanie Owczarski, Betsy Shuford, Tara Duke, Gary Gilkeson, Louis Luttrell, Kathie Hermayer, Jyotika Fernandes, David B Adams, Katherine A Morgan
Islet engraftment after transplantation is impaired by high rates of islet/β cell death caused by cellular stressors and poor graft vascularization. We studied whether cotransplantation of ex vivo expanded autologous bone marrow-derived mesenchymal stem cells (MSCs) with islets is safe and beneficial in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation. MSCs were harvested from the bone marrow of three islet autotransplantation patients and expanded at our current Good Manufacturing Practices (cGMP) facility...
November 21, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29152615/scid-pigs-an-emerging-large-animal-nk-model
#16
Ellis J Powell, Joan E Cunnick, Christopher K Tuggle
Severe Combined ImmunoDeficiency (SCID) is defined as the lack or impairment of an adaptive immune system. Although SCID phenotypes are characteristically absent of T and B cells, many such SCID cellular profiles include the presence of NK cells. In human SCID patients, functional NK cells may impact the engraftment success of life saving procedures such as bone marrow transplantation. However, in animal models, a T cell-, B cell-, NK cell+ environment provides a valuable tool for asking specific questions about the extent of the innate immune system function as well as emerging NK targeted therapies against cancer...
2017: Journal of Rare Diseases Research & Treatment
https://www.readbyqxmd.com/read/29152128/modulation-of-cabozantinib-efficacy-by-the-prostate-tumor-microenvironment
#17
Manisha Tripathi, Srinivas Nandana, Sandrine Billet, Karen A Cavassani, Rajeev Mishra, Leland W K Chung, Edwin M Posadas, Neil A Bhowmick
The tumor microenvironment (TME) is increasingly recognized as the arbiter of metastatic progression and drug resistance in advanced prostate cancer (PCa). Cabozantinib is a potent tyrosine kinase inhibitor (TKI) with reported biological activity in the PCa epithelia, but failed to provide an overall survival benefit in phase 3 clinical trials. However, the promising biologic efficacy of the drug in early trials warranted a better understanding of the mechanism of action, with the goal of improving patient selection for TKI-based therapy such as cabozantinib...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29146574/mast-cell-dependent-il-33-st2-signaling-is-protective-against-the-development-of-airway-hyperresponsiveness-in-a-house-dust-mite-mouse-model-of-asthma
#18
Anna Maria Zoltowska Nilsson, Ying Lei, Mikael Adner, Gunnar P Nilsson
Interleukin-33 (IL-33) and its receptor ST2 have been influentially associated to the pathophysiology of asthma. Due to the divergent roles of IL-33 in regulating mast cell functions, there is a need to further characterize IL-33/ST2-dependent mast cell responses and their significance in the context of asthma. This study aimed to investigate how IL-33/ST2-dependent mast cell responses contribute to the development of airway hyperresponsiveness (AHR) and airway inflammation in a mouse model of house dust mite (HDM) induced asthma...
November 16, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29137845/enumeration-of-bone-marrow-plasmacytoid-dendritic-cells-by-multiparameter-flow-cytometry-as-a-prognostic-marker-following-allogeneic-hematopoietic-stem-cell-transplantation
#19
Ruijun Jeanna Su, Ralph Green, Mingyi Chen
Plasmacytoid dendritic cells (pDCs) promote tolerance in solid organ transplants and hematopoietic stem cell transplantation (HSCT). pDCs originate from CD34(+) hematopoietic progenitors. Following allogeneic hematopoietic stem cell transplant (allo-HSCT), pDC reconstitution in the BM and PB gradually attain levels similar to those in healthy individuals. We have investigated the recovery of pDC following allo-HSCT as a means to predict successful marrow engraftment. We retrospectively studied immune reconstitution of pDC in the BM of 48 patients following allo-HSCT for initial diagnoses of leukemia or other malignancies...
October 31, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29132800/fetal-bone-marrow-homing-of-donor-mesenchymal-stem-cells-after-transamniotic-stem-cell-therapy-trascet
#20
Hester F Shieh, Azra Ahmed, Sarah A Tracy, David Zurakowski, Dario O Fauza
PURPOSE: Donor cell engraftment patterns following transamniotic stem cell therapy (TRASCET) with amniotic fluid mesenchymal stem cells (afMSCs) are incompatible with solely direct amniotic seeding. We sought to determine whether fetal bone marrow is a component of such engraftment and to examine the chronology of afMSC placental trafficking. METHODS: Two groups of Sprague-Dawley rat fetuses received volume-matched intraamniotic injections on gestational day 17 (E17; term E22): either afMSCs labeled with a luciferase reporter gene or luciferase protein alone...
October 12, 2017: Journal of Pediatric Surgery
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