NEW ADVANCES IN STEM CELL TRANSPLANTATION Edited by Taner Demirer New Advances in Stem Cell Transplantation Edited by Taner Demirer Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work Any republication, referencing or personal use of the work must explicitly identify the original source As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher No responsibility is accepted for the accuracy of information contained in the published chapters The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book Publishing Process Manager Masa Vidovic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org New Advances in Stem Cell Transplantation, Edited by Taner Demirer p cm ISBN 978-953-51-0013-3 Contents Preface IX Part Basic Aspects of Stem Cell Transplantation Chapter Generation of Patient Specific Stem Cells: A Human Model System Stina Simonsson, Cecilia Borestrom and Julia Asp Chapter Importance of Non-HLA Gene Polymorphisms in Hematopoietic Stem Cell Transplantation 25 Jeane Visentainer and Ana Sell Chapter Relevance of HLA Expression Variants in Stem Cell Transplantation 39 Britta Eiz-Vesper and Rainer Blasczyk Chapter The T-Cells’ Role in Antileukemic Reactions Perspectives for Future Therapies’ 59 Helga Maria Schmetzer and Christoph Schmid Chapter Determination of Th1/Th2/Th17 Cytokines in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation 83 Adriana Gutiérrez-Hoya, Rubén López-Santiago, Jorge Vela-Ojeda, Laura Montiel-Cervantes, Octavio Rodríguez-Cortes and Martha Moreno-Lafont Chapter Licensed to Kill: Towards Natural Killer Cell Immunotherapy 103 Diana N Eissens, Arnold van der Meer and Irma Joosten Chapter Dendritic Cells in Hematopoietic Stem Cell Transplantation 127 Yannick Willemen, Khadija Guerti, Herman Goossens, Zwi Berneman, Viggo Van Tendeloo and Evelien Smits Chapter Mesenchymal Stem Cells as Immunomodulators in Transplantation 143 Nadia Zghoul, Mahmoud Aljurf and Said Dermime VI Contents Chapter Chapter 10 Part Endovascular Methods for Stem Cell Transplantation Johan Lundberg and Staffan Holmin 159 Dynamic Relationships of Collagen Extracellular Matrices on Cardiac Differentiation of Human Mesenchymal Stem Cells 183 Pearly Yong, Ling Qian, YingYing Chung and Winston Shim Clinical Aspects of Stem Cell Transplantation 197 Chapter 11 Sources of Hematopoietic Stem Cells 199 Piotr Rzepecki, Sylwia Oborska and Krzysztof Gawroński Chapter 12 Cryopreservation of Hematopoietic and Non-Hematopoietic Stem Cells – A Review for the Clinician 231 David Berz and Gerald Colvin Chapter 13 Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukaemia 267 Pier Paolo Piccaluga, Stefania Paolini, Francesca Bonifazi, Giuseppe Bandini, Giuseppe Visani and Sebastian Giebel Chapter 14 Treatment Options in Myelodysplastic Syndromes Klara Gadó and Gyula Domján Chapter 15 Mantle Cell Lymphoma: Decision Making for Transplant 319 Yener Koc and Taner Demirer Chapter 16 Autologous Peripheral Blood Purified Stem Cells Transplantation for Treatment of Systemic Lupus Erythematosus 345 Ledong Sun and Bing Wang Chapter 17 Allogeneic Hematopoietic Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria 355 Markiewicz Miroslaw, Koclega Anna, Sobczyk-Kruszelnicka Malgorzata, Dzierzak-Mietla Monika, Zielinska Patrycja, Frankiewicz Andrzej, Bialas Krzysztof and Kyrcz-Krzemien Slawomira Chapter 18 Intensified Chemotherapy with Stem Cell Support for Solid Tumors in Adults: 30 Years of Investigations Can Provide Some Clear Answers? 371 Paolo Pedrazzoli, Giovanni Rosti, Simona Secondino, Marco Bregni and Taner Demirer Chapter 19 Hematopoietic Stem Cell Transplantation for Malignant Solid Tumors in Children 381 Toshihisa Tsuruta 289 Contents Chapter 20 Stem Cells in Ophthalmology 405 Sara T Wester and Jeffrey Goldberg Chapter 21 Limbal Stem Cell Transplantation and Corneal Neovascularization 443 Kishore Reddy Katikireddy and Jurkunas V Ula Chapter 22 Bone Marrow Stromal Cells for Repair of the Injured Spinal Cord 471 D S Nandoe Tewarie Rishi, Oudega Martin and J Ritfeld Gaby Chapter 23 What Do We Know About the Detailed Mechanism on How Stem Cells Generate Their Mode of Action 495 Peter Riess and Marek Molcanyi Chapter 24 Autologous Stem Cell Infusion for Treatment of Pulmonary Disease 505 Neal M Patel and Charles D Burger Chapter 25 Neurologic Sequealae of Hematopoietic Stem Cell Transplantation (HSCT) 517 Ami J Shah, Tena Rosser and Fariba Goodarzian Chapter 26 Adenoviral Infection – Common Complication Following Hematopoietic Stem Cell Transplantation 533 Iwona Bil-Lula, Marek Ussowicz and Mieczysław Woźniak Chapter 27 A Systematic Review of Nonpharmacological Exercise-Based Rehabilitative Interventions in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation 557 M Jarden VII Preface This book documents the increased number of stem cell-related research, clinical applications, and views for the future The book covers a wide range of issues in cellbased therapy and regenerative medicine, and includes clinical and preclinical chapters from the respected authors involved with stem cell studies and research from around the world It complements and extends the basics of stem cell physiology, hematopoietic stem cells, issues related to clinical problems, tissue typing, cryopreservation, dendritic cells, mesenchymal cells, neuroscience, endovascular cells and other tissues In addition, tissue engineering that employs novel methods with stem cells is explored Clearly, the continued use of biomedical engineering will depend heavily on stem cells, and this book is well positioned to provide comprehensive coverage of these developments This book will be the the main source for clinical and preclinical publications for scientists working toward cell transplantation therapies with the goal of replacing diseased cells with donor cells of various organs, and transplanting those cells close to the injured or diseased target With the increased number of publications related to stem cells and Cell Transplantation, we feel it is important to take this opportunity to share these new developments and innovations describing stem cell research in the cell transplantation field with our worldwide readers Stem cells have a unique ability They are able to self renew with no limit, allowing them to replenish themselves, as well as other cells Another ability of stem cells is that they are able to differentiate to any cell type A stem cell does not differentiate directly to a specialized cell however- there are often multiple intermediate stages A stem cell will first differentiate to a progenitor cell A progenitor cell is similar to a stem cell, although they are limited in the number of times they can replicate, and they are also restricted in which cells they can further differentiate to Serving as a sort of repair system for the body, they can theoretically divide without limit in order to replenish other cells for the rest of the person or animal's natural life When a stem cell divides, each new cell has the potential to either remain a stem cell, or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell Because of the unique abilities of stem cells, as opposed to a typical somatic cell, they are currently the target of ongoing research Research on stem cells is advancing in the X Preface knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms This promising area of science is also leading scientists to investigate the possibility of cell-based therapies to treat disease such as diabetes or heart disease It is often referred to as regenerative medicine or reparative medicine During this last decade, the number of published articles or books investigating the role of stem cells in cell transplantation or regenerative medicine increased remarkably across all sections of the stem cell related journals The largest number of stem cell articles was published mainly in the field of neuroscience, followed by the bone, muscle, cartilage, and hepatocytes Interestingly, in recent years, the number of stem cell articles describing the potential use of stem cell therapy and islet transplantation in diabetes is also slowly increasing, even though this field of endeavor could have one of the greatest clinical and societal impacts Stem cells could have the potential to diminish the problem of the availability of transplantable organs that, today, limits the number of successful large-scale organ replacements Several different methods using stem cells are currently used, but there are still several obstacles that need to be resolved before attempting to use stem cells in the clinic Regarding the transplantation of differentiated cells derived from stem cells, one can argue that there are several regulatory, scientific, and technical issues, such as cell manufacturing procedures, regulatory mechanisms for differentiation, and developing screening methods to avoid developing inappropriate differentiated cells One of the next steps in stem cell therapy is the development of treatments that will function not only at an early stage of transplantation, but will also remain intact throughout the life of the host recipient It will be exciting and interesting for our readers to follow the recent developments in the field of stem cells and cell transplantation, via this book, such as authors’ search for the clues to what pathways are used by stem cells to repair tissue, or what can trigger wound healing, bone growth, and brain repair Although we are close to finding pathways for stem cell therapies in many medical conditions, scientists need to be careful how they use stem cells ethically, and should not rush into clinical trials without carefully investigating the side effects Focus must be on Good Manufacturing Procedures (GMP) and careful monitoring of the long-term effects of transplanted stem cells in the host In conclusion, Cell Transplantation is bridging cell transplantation research in a multitude of disease models as methods and technology continue to be refined The use of stem cells in many therapeutic areas will bring hope to many patients awaiting replacement of malfunctioning organs, or repairing of damaged tissues We hope that this book will be an important tool and reference guide for all scientists worldwide who work in the field of stem cells and cell transplantation Additionally, we hope that it will shed a light upon many important debatable issues in this field AA indicates aplastic anemia, AML, acute myelogenous leukemia; ALL, acute lymphocytic or lymphoblastic leukemia ; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CMML, chronic myelomonocytic leukemia; HD, Hodgkins disease; MDS, myelodysplastic syndrome; MF, myelofibrosis; MM, multiple myeloma; MPS, myeloproliferative syndrome; NHL, Non-Hodgkin lymphoma; PNH, paroxysmal nocturnal hemoglobinuria; WM, waldenstrom macroglobulinemia RPE, Rate of Perceived Exertion; St.v, Stroke Volume; HR, Heart Rate; IG, Intervention Group; IG2, Intervention Group 2; CG, Control Group; TPN, Total Parenteral Nutrition; MHR, Maximal Heart Rate; DM and NDM, Dominant Non Dominant; KPS, Karnofsky Score; PT, Physical therapy; PRO, patient reported outcome; HR-QoL, health related Quality of Life; TR-symptoms, treatment related symptoms; SCT-SAS, Stem cell transplantationSymptom Assessment Scale; EORTC-QLQ-C30 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; HADS, Hospital Anxiety and Depression Scale; FACT-An or FACT-F, Functional Assessment of Cancer therapy – Anemia or Fatigue scale; POMS, Profile of Mood States; MFI, Multidimensional Fatigue Inventory; BFI, Brief Fatigue Inventory; BDI, Beck Depression Inventory; STAI, State Trait Anxiety Inventory; 6MWD, minute walk distance , → no change; ↑ increase; ↓ decrease *median age Results 568 New Advances in Stem Cell Transplantation Table Physical exercise based studies in allogeneic HSCT on aerobic capacity, muscle strength, health-related quality of life and treatment related symptoms A Systematic Review of Nonpharmacological Exercise-Based Rehabilitative Interventions in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation 569 Results 3.1 Exercise-based studies in the allo-HSCT setting In this review, 10 studies met the inclusion criteria (Baumann et al 2011; Carlson et al 2006; Cunningham et al 1986; Defor et al 2007; Inoue et al., 2010; Jarden et al., 2009; Kim and Kim 2006; Mello et al 2003; Shelton et al 2009; Wiskemann et al 2011) Of these, three were from the USA and two from Germany, and respectively, one from Brazil, Canada, Denmark, Japan and South Korea Cunningham et al carried out the very first exercise training trial for the allo-HSCT population in 1986 and although the participants included children and adults (range 14 – 41 years), this study is included in the review because of its focus being in the allo-HSCT setting only Jarden et al published three articles and Kim et al two articles, each based on one trial, however each article has a different focus and purpose All studies were designed as prospective intervention trials that tested an exercise-based program The primary and secondary outcomes were study feasibility and safety; physiological outcomes i.e aerobic, muscle strength and function; psychosocial outcomes i.e health-related QoL, emotional wellbeing; treatment-related symptoms i.e fatigue; and hospital or disease-related outcomes i.e days of hospitalization, creatinine excretion, lymphocyte counts Baseline to post assessment ranged between – 16 weeks [mean 7.3] and one study had follow-up tests to months (Jarden et al 2009) 3.2 Sample characteristics In all, 406 patients with different haematological diseases (AA,, AML, ALL, CLL , CML, CMML, FL, HD, MDS, MF, MM, MPS, NHL, PNH, WM, other lymphomas)1 across 10 Table Intervention phase AA indicates aplastic anemia, AML, acute myelogenous leukemia; ALL, acute lymphocytic or lymphoblastic leukemia ; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CMML, chronic myelomonocytic leukemia; HD, Hodgkins disease; MDS, myelodysplastic syndrome; MF, myelofibrosis; MM, multiple myeloma; MPS, myeloproliferative syndrome; NHL, Non-Hodgkin lymphoma; PNH, paroxysmal nocturnal hemoglobinuria; WM, waldenstrom macroglobulinemia 570 New Advances in Stem Cell Transplantation studies are included in this review The sample size of the studies ranged from 12 to 105 [Mean 50.7] and the patients were of mixed gender between 14 and 71 years [mean 42.6] Cunningham was the only study that included patients less than 18 years of age Four studies were initiated prior to conditioning and throughout the hospitalization period (Baumann et al 2011; Cunningham et al 1986; Defor et al 2007; Jarden et al 2009; Kim and Kim 2006; Wiskemann et al 2011), two studies after marrow engraftment and throughout hospitalization (Mello et al., 2003; Inoue et al., 2010), and three of these continued post alloHSCT (Defor et al 2007; Mello et al 2003; Wiskemann et al 2011) Two studies were initiated post allo-HSCT in the out-patient or home setting, within and 39 months (range 992), respectively (Shelton et al 2009; Carlson et al 2006) The approximate start and endpoint of each intervention is illustrated in Table 3.3 Type of exercise-based interventions The duration of the exercise-based interventions ranged between 4-16 weeks [mean 7.3] For interventions initiated prior to and during hospitalization, of the studies were supervised (Cunningham et al 1986; Mello et al 2003; Kim and Kim 2006; Jarden et al 2009; Inoue et al 2010; Baumann et al 2011) and were partly supervised (DeFor et al 2007, Wiskemann et al 2011) In the out-patient context, Carlson’s study was fully supervised, while Shelton’s study had one supervised and one self-directed study arm The frequency of all interventions ranged between and days/week or daily When reported, the intensity of training in general was between low/mild and comfortable to moderate but not exceeding 70-75% of maximum heart rate or in Rate of Perceived Exertion (RPE) - being somewhat hard In the in-patient context, one study tested strength resistive training (Cunningham et al 1986), one a walking program (treadmill or walking) (Defor et al 2007) and another mixedtype low intensity bed exercises of stretching and relaxation breathing (Kim and Kim 2006), and studies instituted mixed-type exercise up to moderate intensity (Mello et al 2003, Jarden et al 2009, Inoue et al 2010, Wiskemann et al 2011, Baumann et al 2011) by combining aerobic training (treadmill, cycle, walking or stair climbing) with one or more other moderate intensity exercise (range of motion or ADL (activities of daily living), coordination exercises, muscle stretching, resistive exercises with free weights or elastic bands) and low intensity progressive relaxation training and education (Jarden et al 2009) Three studies (Mello et al 2003; Wiskemann et al 2011, Defor et al 2007) continued the programs after hospital discharge In the out-patient only context, one study tested an ergometer cycle program (Carlson et al 2006), and the other, aerobic (cycle or treadmill) and resistive exercises (weight machines) vs selfdirected walking and resistive exercises including patient information regarding exercise safety (Shelton et al 2009) All in all, three studies were unidimensional (one exercise component), of which, two were aerobic training (Carlson et al 2006; DeFor et al 2007), and one resistance training (Cunningham et al 1986), and seven studies had mixed type training (Baumann et al 2011; Inoue et al 2010; Jarden et al 2009; Kim and Kim 2006; Mello et al 2003; Shelton et al 2009; Wiskemann 2011), of which, one was of low intensity (Kim and Kim 2006), and one study included both low and moderate intensity components (Jarden et al 2009) Only two studies incorporated educational (Shelton et al 2009) or psychoeducational (Jarden et al 2009) elements in the program A Systematic Review of Nonpharmacological Exercise-Based Rehabilitative Interventions in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation 571 3.4 Feasibility and safety No adverse events, reactions or injuries were reported, though not all studies reported safety outcomes The overall attrition rates ranged between and 44% (mean 18.7) Program compliance was reported by five studies (Carlson et al 2006; DeFor et al 2007; Jarden et al 2009; Shelton et al 2009; Wiskemann et al 2011) Carlson et al reported an overall 89% compliance Defor et al reported that 24% of all patients had 100% compliance and that 62% of the study’s population exercised at least times/wk for at least 15 during hospitalization and after discharge, respectively Jarden et al reported 90% intervention compliance (range 67-100), and 83% in-hospital and 87% at-home compliance (Wiskemann et al 2011), while Shelton et al reported 75% for the supervised intervention, though did not report for the self-directed intervention Some studies had safety screening parameters, in which contraindication for exercise included platelet counts