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16. Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Author

Mokhtari, S., Baptista, P.M., Vyas, D.A., Freeman, C.J., Moran, E., Brovold, M., Llamazares, G.A., Lamar, Z., Porada, C.D., Soker, S., and Almeida-Porada, G.

Abstract

Despite advances in ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells (CB-HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB-HSPC can be expanded ex vivo in two-dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three-dimensional-liver-extracellular-matrix (3D-ECM) seeded with hepatoblasts, fetal liver-derived (LvSt), or bone marrow-derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D-ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D-ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation. Stem Cells Translational Medicine 2018;7:271–282.

Published
2018

20. Cell and organ bioengineering technology as applied to gastrointestinal diseases

Author

Orlando, G, Bendala, J, Shupe, T, Bergman, C, Bitar, K, Booth, C, Carbone, M, Koch, K, Lerut, J, Neuberger, J, Petersen, B, Ricordi, C, Atala, A, Stratta, R, Soker, S, Soker, S., CARBONE, MARCO, Orlando, G, Bendala, J, Shupe, T, Bergman, C, Bitar, K, Booth, C, Carbone, M, Koch, K, Lerut, J, Neuberger, J, Petersen, B, Ricordi, C, Atala, A, Stratta, R, Soker, S, Soker, S., and CARBONE, MARCO

Abstract

This review illustrates promising regenerative medicine technologies that are being developed for the treatment of gastrointestinal diseases. The main strategies under validation to bioengineer or regenerate liver, pancreas, or parts of the digestive tract are twofold: engineering of progenitor cells and seeding of cells on supporting scaffold material. In the first case, stem cells are initially expanded under standard tissue culture conditions. Thereafter, these cells may either be delivered directly to the tissue or organ of interest, or they may be loaded onto a synthetic or natural three-dimensional scaffold that is capable of enhancing cell viability and function. The new construct harbouring the cells usually undergoes a maturation phase within a bioreactor. Within the bioreactor, cells are conditioned to adopt a phenotype similar to that displayed in the native organ. The specific nature of the scaffold within the bioreactor is critical for the development of this high-function phenotype. Efforts to bioengineer or regenerate gastrointestinal tract, liver and pancreas have yielded promising results and have demonstrated the immense potential of regenerative medicine. However, a myriad of technical hurdles must be overcome before transplantable, engineered organs become a reality.

Published
2013

21. Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix-A Comparative Analysis of Bioartificial Liver Microenvironments

Author

Wang, B., Jakus, A.E., Baptista, P.M., Soker, S., Soto-Gutierrez, A., Abecassis, M.M., Shah, R.N., and Wertheim, J.A.

Abstract

Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the influence of novel three-dimensional bioartificial microenvironments on function and maturation of hepatocyte-like cells differentiated from iPSCs and grown within an acellular, liver-derived extracellular matrix (ECM) scaffold. In parallel, we also compared a bioplotted poly-L -lactic acid (PLLA) scaffold that allows for cell growth in three dimensions and formation of cell-cell contacts but is infused with type I collagen (PLLA-collagen scaffold) alone as a "deconstructed" control scaffold with narrowed biological diversity. iPSC-derived hepatocytes cultured within both scaffolds remained viable, became polarized, and formed bile canaliculi-like structures; however, cells grown within ECM scaffolds had significantly higher P450 (CYP2C9, CYP3A4, CYP1A2) mRNA levels and metabolic enzyme activity compared with iPSC hepatocytes grown in either bioplotted PLLA collagen or Matrigel sandwich control culture. Additionally, the rate of albumin synthesis approached the level of primary cryopreserved hepatocytes with lower transcription of fetal-specific genes, alpha-fetoprotein and CYP3A7, compared with either PLLA-collagen scaffolds or sandwich culture. These studies show that two acellular, three-dimensional culture systems increase the function of iPSC-derived hepatocytes. However, scaffolds derived from ECM alone induced further hepatocyte maturation compared with bioplotted PLLA-collagen scaffolds. This effect is likely mediated by the complex composition of ECM scaffolds in contrast to bioplotted scaffolds, suggesting their utility for in vitro hepatocyte assays or drug discovery. SIGNIFICANCE Through the use of novel technology to develop three-dimensional (3D) scaffolds, the present study demonstrated that hepatocyte-like cells derived via induced pluripotent stem cell (iPSC) technology mature on 3D extracellular matrix scaffolds as a result of 3D matrix structure and scaffold biology. The result is an improved hepatic phenotype with increased synthetic and catalytic potency, an improvement on the blunted phenotype of iPSC-derived hepatocytes, a critical limitation of iPSC technology. These findings provide insight into the influence of 3D microenvironments on the viability, proliferation, and function of iPSC hepatocytes to yield a more mature population of cells for cell toxicity studies and disease modeling.

Published
2016

23. In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells

Author

Rodman, C, primary, Almeida-Porada, G, additional, George, S K, additional, Moon, J, additional, Soker, S, additional, Pardee, T, additional, Beaty, M, additional, Guida, P, additional, Sajuthi, S P, additional, Langefeld, C D, additional, Walker, S J, additional, Wilson, P F, additional, and Porada, C D, additional

Published
2016
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24. Regenerative medicine as applied to solid organ transplantation: current status and future challenges

Author

Orlando, G, Baptista, P, Birchall, M, De Coppi, P, Farney, A, Guimaraes-Souza, N, Opara, E, Rogers, J, Seliktar, D, Shapira-Schweitzer, K, Stratta, R, Atala, A, Wood, K, and Soker, S

Abstract

In the last two decades, regenerative medicine has shown the potential for "bench-to-bedside" translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting-edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using "natural tissue" scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom-made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immunosuppression. This review describes recent advances in the engineering of several key tissues and organs.

Published
2011

27. The influence of extracellular matrix derived from skeletal muscle tissue on the proliferation and differentiation of myogenic progenitor cells ex vivo

Author

Stern, M M, Myers, R L, Hammam, N, Stern, K A, Eberli, D, Kritchevsky, S B, Soker, S, Van Dyke, M, University of Zurich, and Van Dyke, M

Subjects
10062 Urological Clinic, 10022 Division of Surgical Research, 2211 Mechanics of Materials, 1502 Bioengineering, 2502 Biomaterials, 610 Medicine & health, 2503 Ceramics and Composites, 1304 Biophysics
Published
2009

28. Poster presentations

Author

Aksu F, Topacoglu H, Arman C, Atac A, Tetik S, Hasanovic A, Kulenovic A, Mornjakovic Z, Pikula B, Sarac-Hadzihalilovic A, Voljevica A, Bamac B, Colak T, Alemdar M, Dundar G, Selekler M, Dincer O, Colak E, Ozbek A, Kilic C, Kamburoglu K, Ozen T, Kavak V, Kirici Y, Oztas E, Soysal HA, Unur E, Ekinci N, Karaca O, Malakhova O, Kocaoglu M, Toker S, Taser F, Kilincoglu V, Yurtgun MF, Dalcik C, Zeybek A, Baroncini M, Peltier J, Jissendi P, Pruvo JP, Francke JP, Prevot V, Kosif R, Arifoglu Y, Diramali M, Sarsilmaz M, Kose E, Ogeturk M, Akpinar B, Kus I, Meydan S, Kara A, Kurtoglu Z, Tekdemir I, Elhan A, Bas O, Odaci E, Mollaoglu H, Ucok K, Kaplan S, Senoglu M, Nacitarhan V, Kurutas EB, Senoglu N, Altun I, Atli Y, Ozbag D, Karakas S, Bilgin MD, Tellioglu AM, Ozlem S, Akcanal B, Yildiz Y, Gunes H, Kose H, Uzum I, Gundogmus UN, Caglayan C, Pavlova V, Dimitrova M, Georgieva L, Nikolova E, Uzmansel D, Ozturk NC, Saylam CY, Ozgiray E, Orhan M, Cagli S, Zileli M, Ozkan D, Akkaya T, Comert A, Balikci N, Ozdemir E, Gumus H, Ergul Z, Kaya O, Altun S, Unlu RE, Orbay H, Kim DI, Han SH, Kim YS, Kim HJ, Lee KS, Elcioglu O, Ozden H, Guven G, Imre N, Yalcin B, Ozan H, Akyer P, Guvencer M, Karatosun V, Sagoo MG, Aland RC, Ustuner D, Ustuner MC, Ai J, Ghazi SR, Mansouri SH, Tuncer MC, Aluclu MU, Karabulut O, Hatipoglu ES, Nazaroglu H, Icke C, Akbay E, Gunay T, Icke S, Yildiz S, Yazar F, Barlas BO, Zahoi DE, Kavakli A, Tas U, Dabak DO, Sapmaz HI, Kocabiyik N, Ozer CM, Ozcan A, Elevli L, Desdicioglu K, Alanbay I, Govsa F, Akdogan I, Kiroglu Y, Onur S, Evcil EH, Cankara N, Malas MA, Kalcioglu MT, Duman S, Ulcay T, Uzun A, Karabulut Z, Barut C, Sevinc O, Yurdakan G, Kacar D, Erdogan AR, Kurt H, Demir B, Saltan M, Burukoglu D, Degirmenci I, Erdogan A, Damar O, Is M, Bayramoglu G, Kabay S, Uysal O, Senturk H, Bayramoglu A, Ozbayar C, Kutlu A, Canbek M, Cevli SC, Hancerlioglu O, Koplay M, Aksakalli E, Dikici F, Kale A, Gayretli O, Gurses IA, Ozdemir ST, Ercan I, Baskan EB, Yilmaz M, Ozkaya G, Saricaoglu H, Erturk M, Kayalioglu G, Uzel M, Kahraman G, Tanyeli E, Soyluoglu AI, Tacar O, Demirant A, Bilgin M, Karadede A, Aktas A, Koyuncu E, Sulak O, Albay S, Ozguner G, Ozbek E, Ozturk AH, Demirci T, Ciftcioglu E, Demir MT, Kopuz C, Eroglu E, Gedikli S, Ozyurek H, Nural MS, Incesu L, Ogur G, Kara E, Celebi B, Yildiz A, Altunkaynak BZ, Kuvat SV, Tagil SM, Ertekin C, Uysal H, Bademkiran F, Albayrak N, Esmer AF, Coskun NK, Sindel M, Kizilay F, Yalin S, Karapinar N, Tokdemir M, Karakurt L, Tumkaya L, Korkmaz A, Ayas B, Ciftci N, Terzi Y, Baran O, Nergiz Y, Akkus M, Aluclu U, Topal AE, Yuksel D, Acar HI, Kendir S, Hekimoglu E, Basman D, Ozener B, Pelin C, Zagyapan R, Kurkcuoglu A, Koc M, Erdinc M, Erdinc L, Kelle I, Sancakdar E, Cetin N, Tunik S, Yildirim A, Kaplanoglu I, Ayaz E, Ilhan N, Okumus M, Yuksel KZ, Ciralik H, Yilmaz Z, Gumusalan Y, Gamsizkan M, Kazkayasi M, Unver Dogan N, Uysal II, Karalezli A, Fazliogullari Z, Buyukmumcu M, Bozkurt MC, Cicekcibasi AE, Demiryurek D, Ozsoy MH, Tuccar E, Baran OP, Soker S, Bahceci S, Nasir Y, Yilmaz MT, Cicekcibasi EA, Ulusoy M, Gunaslan P, Bilge N, Akkaya M, Genc A, Akcer S, Gonul Y, Cosar E, Koken G, Ari I, Bakirci S, Kafa IM, Uysal M, Karabulut AK, Keles B, Emlik D, Uyar Y, Ozturk K, Yilmaz NA, Salbacak A, Kacira BK, Arazi M, Demirci S, Kiresi D, Gumus S, Seker M, Uyar M, Astaneh ME, Khorshid A, Uygur R, Songur A, Sonmez OF, Dogan KH, Kolcu G, Iliescu M, Bordei P, Iliescu D, Ciobotaru C, Lucescu V, Covaleov A, Ionescu C, Guirao M, Páramo E, Mutuberria R, Sánchez-Montesinos I, Roda O, Girón F, Lopez-Soler M, Campos-López R, Guirao-Piñeiro M, Pascual-Morenilla MT, Sanchez-Montesinos I, Pascual MT, Garzon I, Serrato D, Nieto-Aguilar R, Sanchez-Quevedo M, Ozdemir MB, Ozean RH, Bagdatli D, Adiguzel E, Dogan Z, Aycan O, Vardi N, Erkal HS, Ozturk H, Mocanu S, Stefanescu C, Ionescu A, Talpes R, Sapte E, Dina C, Surdu L, Bulbuc I, Medina MT, Medina J, López-Soler M, Martin-Oviedo C, Lowy-Benoliel A, Maranillo E, Martinez-Guirado T, Sañudo J, Scola B, Vazquez T, Arráez-Aybar LA, Conejo-Menor JL, Gonzáles-Gómez CC, Torres-García AJ, Nasu H, Chiba S, Gutierrez-Semillera M, Paksoy Y, Kalaycioglu A, Yildirim M, Ozyasar A, Ozdogmus O, Cakmak YO, Verimli U, Cavdar S, Yildizhan B, Aktan Ikiz ZA, Ucerler H, Ozgur Z, Yilmaz S, Demirtas A, Mavili E, Hacialiogullari M, Susar H, Arslan S, Aycan K, Ozkaya V, Pilmane M, Boka S, Ortug G, Ramirez C, Pascual-Font A, Valderrama-Canales F, Kucukalic A, Kapur E, Talovic E, Baca V, Grill R, Horak Z, Kachlik D, Dzupa V, Konarik M, Knize J, Veleminsky P, Smrzova T, Otcenasek M, Chmelova J, Kheck M, Cupka T, Hnatek L, van der Meijs F, Cech P, Musil V, Ozkan HM, Muratli SK, Tayefi H, Ergur I, Kiray A, Toktas M, Alkoc O, Acar T, Uzun I, Ozen OA, Aycicek A, Alkoc OA, Unlu M, Corumlu U, Ikiz IC, Oygucu IH, Sendemir E, Kaner T, Caglar V, Eser O, Iyigun O, Pirzirenli G, Kaya AH, Aydin ME, Celik F, True H, Ozkaya S, Ergur BU, Zeybek G, Bacakoglu K, Tadjalli M, Poostpasand A, Mansouiri SH, Allahvaisi O, Soleimanirad J, Nikkhoo B, Nagato Y, Haruki Y, Yazawa K, Okazaki T, Haida M, Imai Y, Peirouvi T, Mahzad-Sadaghiani M, Noroozinia F, Siamak S, Farjah G, Mola S, Biegaj E, Skadorwa T, Pawlewicz K, Kapolka R, Chachulska A, Zabicka J, Krasowska A, Prusik A, Jaczewski G, Kolesnik A, Taghavi MM, Alavi SH, Moallem SA, Safikhani Z, Panahi M, Dabiri S, Shekaari MA, Latorre R, Soria F, Lopez-Albors O, Sarria R, Ayala I, Serrano I, Perez-Cuadrado E, Musienko V, Tkachenko D, Colakoglu N, Kus MA, Jalali M, Nikravesh MR, Moeen AA, Karimfar MH, Rafighdoost H, Mohammadi S, Korneeva M, Rafighdoust H, Lovasova K, Bolekova A, Kluchova D, Sulla I, Kapitonova MY, Syed Ahmad Fuad SB, Jayakaran F, Shams AR, Aghaee F, Baqer Z, Faroki M, Das S, Kassim N, Latiff A, Suhaimi F, Ghafar N, Hlaing KP, Maatoq I, Othman F, Kiray M, Bagriyanik HA, Pekcetin C, Ozogul C, Fidan M, Sun F, Sanchez-Margallo F, Gil F, Crisostomo V, Uson J, Ramirez G, Turamanlar O, Kirpiko O, Haktanir A, Climent S, Losilla S, Climent M, Sarikcioglu L, Senol Y, Yildirim FB, Utuk A, Kunicki J, Pasbakhsh P, Omidi N, Omidi H, Nazhvani FD, Ghalebi SR, Javan N, Mohagery A, Bideskan AR, Taheri MM, Fazel AR, Tiengo C, Macchi V, Stecco C, Porzionato A, Mazzoleni F, De Caro R, Clemente A, Morra A, Greco P, Pavan P, Natali A, Demir M, Dokur M, Acer N, Mavi A, Matveeva N, Lazarova D, Korneti K, Jovevska S, Jurkovik D, Papazova M, Havasi M, Alboghobeish N, Savari A, Salamat N, Sharifi M, Kwak HH, Hu KS, Kim GC, Park BS, Sinav A, Gulati AK, Gulati NK, Alshammary H, Nazhvani SD, Vafafar A, Esmaeilpour T, Bahmanpour S, Elyasi L, Monabbati A, Ghanadi M, Paryani MR, Gilanpour H, Amirsam B, Omaña RE, López SG, De la Garza Castro O, Vega EU, Lopez SG, Talebpour F, Golmohammadi R, Dashti G, Atlasi MA, Mehdizadeh M, Bahadori MH, Joghataei MT, Hatami L, Boroujeni MB, Estakhr J, Esfandiary E, Marzban M, Bakhtiary M, Modiry N, Jafarpur M, Mofidpur H, Mahmoudian A, Jafarpour M, Mahmoudian AR, Sanjarmousavi N, Doassans I, Sorrenti N, Decuadro G, Saibene A, Poumayrac M, Laza S, Almiron C, Vergara ME, Soria V, Lasa S, Perez A, Castro G, Maria AS, Soleimani M, Katebi M, Bakhshayesh M, Oner M, Halici M, Yikilmaz A, Guney A, Turk Y, Edizer M, Beden U, Icten N, Afshar M, Hasanzadeh Taheri MM, Moalem A, Golalipour MJ, Tamizi A, Ahi M, Mohammadpour S, Maiery A, Acikel C, Ulkur E, Karagoz H, Celikoz B, Bedi K, Ginus P, Golalipoor MJ, Mohammadi MR, Jhand P, Mansourian AR, Hosseinpoor K, Keshtkar AA, Alsaffar R, Balajadeh BK, Ghafari S, Azarhosh R, Fazeli SA, Jahanshahi M, Gharravi AM, Alicioglu B, Karakas HM, Harma A, Yang HM, Won SY, Lee JG, Lee JY, Kim YR, Song WC, Koh KS, Hwang EN, Choi HG, Kim SH, Kim SY, Hur MS, Ulucam E, Celbis O, Kim DH, Hong HS, Choi JH, Park JT, Kim HC, Abbasi H, Hosseinipanah SM, Hosseini M, Amani A, Ashrafi HR, Sadeghimehr M, Sheverdin V, Amani Z, Ashrafi A, Ashrafi AR, Javad H, Kachap MJ, Poumayrac MC, Almirón C, Rivara A, Sirilo A, Freire D, Cirillo A, Veragara ME, Krmek V, Krmek N, Jo-Osvatic A, Nikolic V, Radic R, Tubbs RS, Loukas M, Fogg Q, Ashwood N, Cilingiroglu S, Ozbakir C, Mazoochi T, Sabanciogullari V, Gumus C, Erdil FH, Cimen M, Moodi H, Ghiasi F, Akbari A, Hami J, Khazei M, Haghparast E, Mitsakis I, Anastasiou A, Mitsakis M, Sianou K, Hainoglou R, Francisco M, Mitsaki C, Konstantinidi M, Prapa S, Leksan I, Mrcela T, Selthofer R, Kermanian F, Ahmadpoor ME, Dalili N, Elian AH, Moaiery A, Jamalpour Z, Nourani MR, Asgari A, Hassanzadeh Taheri MM, Ebrahimzadeh A, Eftekharvaghefi SH, Mohammadi A, Sheibani V, Nematollahi-Mahani SN, Latifpour M, Deilami M, Soroure-Azimzadeh B, Nabipour F, Najafipour H, Nakhaee N, Yaghoobi M, Eftekharvaghefi R, Salehinejad P, Azizi H, Riasi HR, Nobakht M, Asalgoo S, Rahbar R, Najafzadeh N, Moosavizadeh K, Ezzatabadypour M, Majidi M, Malekpor-Afshar R, Karimzade F, Hoseini M, Bayat M, Gorgi A, Nezhadi A, Bakhtiari M, Jazi HR, Jafaryan M, Haghir H, Rahimi S, Rassouli FB, Gorji A, Habibi A, Pouya F, Mousavi A, Rajabalian S, Abolidokht A, Khanlarkhani N, Naderian H, Berjis N, Namavar MR, Talaei T, Mazaheri Z, Monabati A, Kosar MI, Karacan K, Chegini H, Nikzad H, Ayhan E, Ustundag S, Akkin SM, Ogut T, Rayegan P, Meibodi MA, Ghaem RM, Zargarpoor R, Eftekhar Vaghefi SH, Moshkdanian G, Poya F, Kohestani H, Abarghoeai RR, Abarghoeai PR, Mahmodi AA, Poraboli A, Kohestani HR, Vaghefi RE, Eftekhar Vaghefy SH, Vaghefy RE, Saba M, Javadnia F, Zhaleh M, Nezhad DB, Gholami MR, Piagkou M, Aikaterini VK, Piagkos G, Douvetzemis S, Skandalakis P, Anagnostopoulou S, Papadopoulos N, Celik HH, Tatar I, Tatar EC, Mocan BO, Sargon MF, Denk CC, Rasoolijazi H, Joghataie MT, Roghani M, Dinc G, Kurklu M, Ozboluk S, Komurcu M, Koebke J, Balioglu MB, Kaygusuz MA, Bozkus FS, Korkmaz O, Bayram SB, Can MA, Nasiri E, Jafar-Kazemi K, Maghoul S, Amini A, Hassanzade MM, Davari MH, Van Hoof T, Gomes GT, Audenaert E, Verstraete K, Kerckaert I, D'Herde K, Benninger B, Hedley G, Filipoiu FM, Tarta E, Enyedi M, Pantu C, Stanciulescu R, Skobowiat C, Calka J, Majewski M, Rezaian M, Yaghoobfar A, Hamedi S, and Shomali T

Published
2009

29. Isolation of Clonal amniotic stem cell lines with potential for therapy

Author

DE COPPI, Paolo, BARTSCH G., Jr, Siddiqui, Mm, Xu, T, Santos, Cc, Perin, L, Mostoslavsky, G, Serre, Ac, Snyder, Ey, Yoo, Jj, Furth, M, Soker, S, and Atala, A.

Subjects
Regenerative me-dicine, kidney, stem cells, kidney, amniotic fluid, stem cells, gene expression, cell lineage, Tissue engineering, gene expression, amniotic fluid, cell lineage
Published
2007

37. Ab initio calcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk for Pneumocystis jirovecii pneumonia

Author

UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Orlando, Giuseppe, Lerut, Jan, Tariciotti, L., Manzia, T. M., Gravante, G., Sorge, R., Manuelli, M., Pisani, F., Di Cocco, P., Scelzo, C., Burke, G. M., Soker, S., Baiocchi, L., Angelico, M., Tisone, G., UCL - Cliniques universitaires Saint-Luc, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service de chirurgie et transplantation abdominale, Orlando, Giuseppe, Lerut, Jan, Tariciotti, L., Manzia, T. M., Gravante, G., Sorge, R., Manuelli, M., Pisani, F., Di Cocco, P., Scelzo, C., Burke, G. M., Soker, S., Baiocchi, L., Angelico, M., and Tisone, G.

Abstract

At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based monotherapy immunosuppression (IS) is the standard of treatment after liver transplantation (LT). As the net state of IS determines the onset of Pneumocystis jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak impairment of the immune function, as determined by the above-mentioned IS, the host is not overexposed to the risk for PCP and consequently the specific anti-PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we retrospectively investigated the incidence of PCP in 203 LT patients who did not receive anti-PCP prophylaxis because they were under monotherapy IS. The primary endpoint of the study was the incidence of PCP during the first 12 months following LT; secondary endpoints were the incidence of acute rejection requiring additional IS and of CMV infection. No cases of PCP were recorded. The incidence of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that monotherapy IS after LT may nullify the risk for PCP even in the absence of any specific prophylaxis.

Published
2010

39. In vitroand in vivoassessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells

Author

Rodman, C, Almeida-Porada, G, George, S K, Moon, J, Soker, S, Pardee, T, Beaty, M, Guida, P, Sajuthi, S P, Langefeld, C D, Walker, S J, Wilson, P F, and Porada, C D

Abstract

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitrocolony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

Published
2017
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42. Ab initiocalcineurin inhibitor-based monotherapy immunosuppression after liver transplantation reduces the risk forPneumocystis jiroveciipneumonia

Author

Orlando, G., primary, Tariciotti, L., additional, Manzia, T.M., additional, Gravante, G., additional, Sorge, R., additional, Manuelli, M., additional, Pisani, F., additional, Di Cocco, P., additional, Scelzo, C., additional, Burke, G.M., additional, Soker, S., additional, Baiocchi, L., additional, Lerut, J., additional, Angelico, M., additional, and Tisone, G., additional

Published
2010
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49. Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1.

Author

Mäkinen, Taija, Olofsson, B, Karpanen, T, Hellman, U, Soker, S, Klagsbrun, M, Eriksson, U, Alitalo, K, Mäkinen, Taija, Olofsson, B, Karpanen, T, Hellman, U, Soker, S, Klagsbrun, M, Eriksson, U, and Alitalo, K

Abstract

Vascular endothelial growth factor B (VEGF-B) is expressed in various tissues, especially strongly in the heart, and binds selectively to one of the VEGF receptors, VEGFR-1. The two splice isoforms, VEGF-B(167) and VEGF-B(186), have identical NH(2)-terminal cystine knot growth factor domains but differ in their COOH-terminal domains which give these forms their distinct biochemical properties. In this study, we show that both splice isoforms of VEGF-B bind specifically to Neuropilin-1 (NRP1), a receptor for collapsins/semaphorins and for the VEGF(165) isoform. The NRP1 binding of VEGF-B could be competed by an excess of VEGF(165). The binding of VEGF-B(167) was mediated by the heparin binding domain, whereas the binding of VEGF-B(186) to NRP1 was regulated by exposure of a short COOH-terminal proline-rich peptide upon its proteolytic processing. In immunohistochemistry, NRP1 distribution was found to be overlapping or adjacent to known sites of VEGF-B expression in several tissues, in particular in the developing heart, suggesting the involvement of VEGF-B in NRP1-mediated signaling.

Published
1999

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