A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

Science.gov (United States)

Okon, Elena B.; Karimi-Abdolrezaee, Soheila; Hill, Caitlin E.; Sparling, Joseph S.; Plemel, Jason R.; Plunet, Ward T.; Tsai, Eve C.; Baptiste, Darryl; Smithson, Laura J.; Kawaja, Michael D.; Fehlings, Michael G.; Kwon, Brian K.

2011-01-01

Abstract Cell transplantation therapies have become a major focus in pre-clinical research as a promising strategy for the treatment of spinal cord injury (SCI). In this article, we systematically review the available pre-clinical literature on the most commonly used cell types in order to assess the body of evidence that may support their translation to human SCI patients. These cell types include Schwann cells, olfactory ensheathing glial cells, embryonic and adult neural stem/progenitor cells, fate-restricted neural/glial precursor cells, and bone-marrow stromal cells. Studies were included for review only if they described the transplantation of the cell substrate into an in-vivo model of traumatic SCI, induced either bluntly or sharply. Using these inclusion criteria, 162 studies were identified and reviewed in detail, emphasizing their behavioral effects (although not limiting the scope of the discussion to behavioral effects alone). Significant differences between cells of the same “type” exist based on the species and age of donor, as well as culture conditions and mode of delivery. Many of these studies used cell transplantations in combination with other strategies. The systematic review makes it very apparent that cells derived from rodent sources have been the most extensively studied, while only 19 studies reported the transplantation of human cells, nine of which utilized bone-marrow stromal cells. Similarly, the vast majority of studies have been conducted in rodent models of injury, and few studies have investigated cell transplantation in larger mammals or primates. With respect to the timing of intervention, nearly all of the studies reviewed were conducted with transplantations occurring subacutely and acutely, while chronic treatments were rare and often failed to yield functional benefits. PMID:20146557

Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

OpenAIRE

Gunawardana, Subhadra C.; Piston, David W.

2012-01-01

Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized gluco...

Early embryonic development and transplantation in tree shrews

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Lan-Zhen YAN

2016-07-01

Full Text Available As a novel experimental animal model, tree shrews have received increasing attention in recent years. Despite this, little is known in regards to the time phases of their embryonic development. In this study, surveillance systems were used to record the behavior and timing of copulations; embryos at different post-copulation stages were collected and cultured in vitro; and the developmental characteristics of both early-stage and in vitro cultured embryos were determined. A total of 163 females were collected following effective copulation, and 150 were used in either unilateral or bilateral oviduct embryo collections, with 307 embryos from 111 females obtained (conception rate=74%. Among them, 237 embryos were collected from 78 females, bilaterally, i.e., the average embryo number per female was 3.04; 172 fertilized eggs collected from 55 females, bilaterally, were cultured for 24-108 h in vitro for developmental observations; finally, 65 embryos from 23 bilateral cases and 70 embryos from 33 unilateral cases were used in embryo transplantation.

The Postischemic Environment Differentially Impacts Teratoma or Tumor Formation After Transplantation of Human Embryonic Stem Cell-Derived Neural Progenitors

Czech Academy of Sciences Publication Activity Database

Seminatore, CH.; Polentes, J.; Ellman, D.; Kozubenko, Nataliya; Itier, V.; Tine, S.; Tritschler, L.; Brenot, M.; Guidou, E.; Blondeau, J.; Lhuillier, M.; Bugi, A.; Aubry, L.; Jendelová, Pavla; Syková, Eva; Perrier, A. L.; Finsen, B.; Onteniente, B.

2010-01-01

Roč. 41, č. 1 (2010), s. 153-159 ISSN 0039-2499 Institutional research plan: CEZ:AV0Z50390703 Keywords : brain transplantation * human embryonic stem cells * neural differentiation Subject RIV: FH - Neurology Impact factor: 5.756, year: 2010

Stem cell biology and cell transplantation therapy in the retina.

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Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo

2010-01-01

Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocyst stage embryos, have the ability to differentiate into any cell type in the body and to grow indefinitely while maintaining pluripotency. During development, cells undergo progressive and irreversible differentiation into specialized adult cell types. Remarkably, in spite of this restriction in potential, adult somatic cells can be reprogrammed and returned to the naive state of pluripotency found in the early embryo simply by forcing expression of a defined set of transcription factors. These induced pluripotent stem (iPS) cells are molecularly and functionally equivalent to ES cells and provide powerful in vitro models for development, disease, and drug screening, as well as material for cell replacement therapy. Since functional impairment results from cell loss in most central nervous system (CNS) diseases, recovery of lost cells is an important treatment strategy. Although adult neurogenesis occurs in restricted regions, the CNS has poor potential for regeneration to compensate for cell loss. Thus, cell transplantation into damaged or diseased CNS tissues is a promising approach to treating various neurodegenerative disorders. Transplantation of photoreceptors or retinal pigment epithelium cells derived from human ES cells can restore some visual function. Patient-specific iPS cells may lead to customized cell therapy. However, regeneration of retinal function will require a detailed understanding of eye development, visual system circuitry, and retinal degeneration pathology. Here, we review the current progress in retinal regeneration, focusing on the therapeutic potential of pluripotent stem cells.

Ambivalent journeys of hope: embryonic stem cell therapy in a clinic in India.

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Prasad, Amit

2015-03-01

Stem cell therapy in non-Western countries such as India has received a lot of attention. Apart from media reports, there are a number of social science analyses of stem cell policy, therapy, and research, their ethical implications, and impact of advertising on patients. Nevertheless, in the media reports as well as in academic studies, experiences of patients, who undertake overseas journeys for stem cell therapy, have largely been either ignored or presented reductively, often as a "false hope." In this article, I analyze the experiences of patients and their "journeys of hope" to NuTech Mediworld, an embryonic stem cell therapy clinic in New Delhi, India. My analysis, which draws on my observations in the clinic and patients' experiences, instead of seeking to adjudicate whether embryonic stem cell therapy in clinics such as NuTech is right or wrong, true or false, focuses on how patients navigate and contest these concerns. I utilize Gilles Deleuze and Felix Guattari's "concepts," lines of flight and deterritorialization, to highlight how embryonic stem cell therapy's "political economy of hope" embodies deterritorialization of several "regimes of truth" and how these deterritorializations impact patients' experiences. © The Author(s) 2014.

Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis.

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Ren, Hongmiao; Chen, Jichuan; Wang, Yinan; Zhang, Shichang; Zhang, Bo

2013-01-01

Stem cell-based regenerative therapy is a potential cellular therapeutic strategy for patients with incurable brain diseases. Embryonic neural stem cells (NSCs) represent an attractive cell source in regenerative medicine strategies in the treatment of diseased brains. Here, we assess the capability of intracerebral embryonic NSCs transplantation for C57BL/6J mice with presbycusis in vivo. Morphology analyses revealed that the neuronal rate of apoptosis was lower in the aged group (10 months of age) but not in the young group (2 months of age) after NSCs transplantation, while the electrophysiological data suggest that the Auditory Brain Stem Response (ABR) threshold was significantly decreased in the aged group at 2 weeks and 3 weeks after transplantation. By contrast, there was no difference in the aged group at 4 weeks post-transplantation or in the young group at any time post-transplantation. Furthermore, immunofluorescence experiments showed that NSCs differentiated into neurons that engrafted and migrated to the brain, even to sites of lesions. Together, our results demonstrate that NSCs transplantation improve the auditory of C57BL/6J mice with presbycusis.

Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

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Yoshida, Toshiyuki; Washio, Kaoru; Iwata, Takanori; Okano, Teruo; Ishikawa, Isao

2012-01-01

It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy. PMID:22315604

Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

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Toshiyuki Yoshida

2012-01-01

Full Text Available It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy.

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

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Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Terapia nutricional no transplante hepático Nutritional therapy in liver transplantation

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Mônica Beatriz PAROLIN

2002-04-01

Full Text Available Racional - Deficiências nutricionais, por vezes graves, são comuns em pacientes com insuficiência hepática, candidatos a transplante de fígado. A terapia nutricional pode corrigir total ou parcialmente tais deficiências, melhorando as condições clínicas e o prognóstico desses indivíduos, frente ao grande desafio do transplante hepático. Objetivos - Breve revisão do papel do fígado no metabolismo dos diversos nutrientes. Descrição dos métodos de avaliação do estado nutricional, traçando-se as bases da terapia nutricional segundo condições hepáticas diversas, no pré e pós-transplante, em relação às necessidades calóricas e dos diversos nutrientes. Apresentação de intervenções nutricionais, no controle das complicações metabólicas resultantes do uso de drogas imunossupressoras. Conclusão - A terapia nutricional é valiosa aliada no tratamento clínico de pacientes candidatos ou já submetidos ao transplante hepático, contribuindo para um prognóstico favorável e para a melhora da qualidade de vida desses indivíduos.Background - Malnutrition, sometimes severe is common in patients with chronic hepatic diseases who are candidates for liver transplantation. Nutritional therapy can induce partial or total correction of such deficiencies, improving clinical conditions and prognosis of patients who face the great defiance of liver transplantation. Aims - Brief revision of hepatic role in the metabolism of several nutrients. Description of available methods of dietary therapy and its application both under different abnormal hepatic conditions and pre and post-transplant periods. The role of nutritional intervention in metabolic side effects due to immunosuppressive drugs. Conclusion - Nutritional therapy is a valuable adjuvant resource to the clinical treatment of candidates and submitted patients to hepatic transplantation providing better prognosis and improved life quality.

Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy

OpenAIRE

Yamada, Satsuki; Nelson, Timothy J.; Crespo-Diaz, Ruben J.; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

2008-01-01

Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K+ (KATP) channel sub-units. Embryonic stem cell therapy demonstrates benefit in ischemi...

Embryonic kidney function in a chronic renal failure model in rodents.

Science.gov (United States)

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic.

Science.gov (United States)

Whiting, Paul; Kerby, Julie; Coffey, Peter; da Cruz, Lyndon; McKernan, Ruth

2015-10-19

Since the first publication of the derivation of human embryonic stem cells in 1998, there has been hope and expectation that this technology will lead to a wave of regenerative medicine therapies with the potential to revolutionize our approach to managing certain diseases. Despite significant resources in this direction, the path to the clinic for an embryonic stem-cell-based regenerative medicine therapy has not proven straightforward, though in the past few years progress has been made. Here, with a focus upon retinal disease, we discuss the current status of the development of such therapies. We also highlight some of our own experiences of progressing a retinal pigment epithelium cell replacement therapy towards the clinic. © 2015 The Author(s).

Amniotic fluid stem cells: a promising therapeutic resource for cell-based regenerative therapy.

Science.gov (United States)

Antonucci, Ivana; Pantalone, Andrea; Tete, Stefano; Salini, Vincenzo; Borlongan, Cesar V; Hess, David; Stuppia, Liborio

2012-01-01

Stem cells have been proposed as a powerful tool in the treatment of several human diseases, both for their ability to represent a source of new cells to replace those lost due to tissue injuries or degenerative diseases, and for the ability of produce trophic molecules able to minimize damage and promote recovery in the injured tissue. Different cell types, such as embryonic, fetal or adult stem cells, human fetal tissues and genetically engineered cell lines, have been tested for their ability to replace damaged cells and to restore the tissue function after transplantation. Amniotic fluid -derived Stem cells (AFS) are considered a novel resource for cell transplantation therapy, due to their high renewal capacity, the "in vitro" expression of embryonic cell lineage markers, and the ability to differentiate in tissues derived from all the three embryonic layers. Moreover, AFS do not produce teratomas when transplanted into animals and are characterized by a low antigenicity, which could represent an advantage for cell transplantation or cell replacement therapy. The present review focuses on the biological features of AFS, and on their potential use in the treatment of pathological conditions such as ischemic brain injury and bone damages.

Antibody-mediated rejection across solid organ transplants: manifestations, mechanisms, and therapies.

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Valenzuela, Nicole M; Reed, Elaine F

2017-06-30

Solid organ transplantation is a curative therapy for hundreds of thousands of patients with end-stage organ failure. However, long-term outcomes have not improved, and nearly half of transplant recipients will lose their allografts by 10 years after transplant. One of the major challenges facing clinical transplantation is antibody-mediated rejection (AMR) caused by anti-donor HLA antibodies. AMR is highly associated with graft loss, but unfortunately there are few efficacious therapies to prevent and reverse AMR. This Review describes the clinical and histological manifestations of AMR, and discusses the immunopathological mechanisms contributing to antibody-mediated allograft injury as well as current and emerging therapies.

Use of polyclonal/monoclonal antibody therapies in transplantation.

Science.gov (United States)

Yeung, Melissa Y; Gabardi, Steven; Sayegh, Mohamed H

2017-03-01

For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation. Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection. It also provides examples of promising novel mAb therapies, and discusses the potential for future mAb development in transplantation. Expert opinion: The broad capability of antibodies, in parallel with our growing ability to synthetically modulate them, offers exciting opportunities to develop better biologic therapeutics. In order to do so, we must further our understanding about the basic biology underlying allograft rejection, and gain better appreciation of how characteristics of therapeutic antibodies affect their efficacy.

Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse model of Parkinson's disease.

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Mariana eAcquarone

2015-04-01

Full Text Available Parkinson’s disease (PD is an incurable progressive neurodegenerative disorder. Clinical presentation of PD stems largely from the loss of dopaminergic neurons in the nigrostriatal dopaminergic pathway, motivating experimental strategies aimed at replacing dopaminergic innervation by cellular therapy. Transplantation of dopaminergic neurons derived from embryonic stem cells significantly improves motor functions in rodent and non-human primate models of PD. However, protocols to generate dopaminergic neurons from embryonic stem cells generally meet with low efficacy and high risk of teratoma development upon transplantation. To address these issues, we have pre-treated undifferentiated mouse embryonic stem cells (mESCs with the DNA alkylating agent mitomycin C (MMC before transplantation. MMC treatment of cultures prevented tumor formation in a 12-week follow-up after mESCs were injected in nude mice. In 6-OH-dopamine-lesioned mice, intrastriatal injection of MMC-treated mESCs markedly improved motor function without tumor formation for as long as 15 months. Furthermore, we show that halting mitotic activity of undifferentiated mESCs induces a four-fold increase in dopamine release following in vitro differentiation. Our findings indicate that treating mESCs with mitomycin C prior to intrastriatal transplant is an effective strategy that could be further investigated as a novel alternative for treatment of Parkinson's disease.

Transplantation Tolerance Induction: Cell Therapies and Their Mechanisms

OpenAIRE

Scalea, Joseph R.; Tomita, Yusuke; Lindholm, Christopher R.; Burlingham, William

2016-01-01

Cell based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types, are being tested as ...

Current trends in immunosuppressive therapies for renal transplant recipients.

Science.gov (United States)

Lee, Ruth-Ann; Gabardi, Steven

2012-11-15

Current trends in immunosuppressive therapies for renal transplant recipients are reviewed. The common premise for immunosuppressive therapies in renal transplantation is to use multiple agents to work on different immunologic targets. The use of a multidrug regimen allows for pharmacologic activity at several key steps in the T-cell replication process and lower dosages of each individual agent, thereby producing fewer drug-related toxicities. In general, there are three stages of clinical immunosuppression: induction therapy, maintenance therapy, and treatment of an established acute rejection episode. Only immunosuppressive therapies used for maintenance therapy are discussed in detail in this review. The most common maintenance immunosuppressive agents can be divided into five classes: (1) the calcineurin inhibitors (CNIs) (cyclosporine and tacrolimus), (2) costimulation blockers (belatacept), (3) mammalian target of rapamycin inhibitors (sirolimus and everolimus), (4) antiproliferatives (azathioprine and mycophenolic acid derivatives), and (5) corticosteroids. Immunosuppressive regimens vary among transplantation centers but most often include a CNI and an adjuvant agent, with or without corticosteroids. Selection of appropriate immunosuppressive regimens should be patient specific, taking into account the medications' pharmacologic properties, adverse-event profile, and potential drug-drug interactions, as well as the patient's preexisting diseases, risk of rejection, and medication regimen. Advancements in transplant immunosuppression have resulted in a significant reduction in acute cellular rejection and a modest increase in long-term patient and graft survival. Because the optimal immunosuppression regimen is still unknown, immunosuppressant use should be influenced by institutional preference and tailored to the immunologic risk of the patient and adverse-effect profile of the drug.

Adoptive regulatory T cell therapy: challenges in clinical transplantation.

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Safinia, Niloufar; Sagoo, Pervinder; Lechler, Robert; Lombardi, Giovanna

2010-08-01

The identification and characterisation of regulatory T cells (Tregs) has recently opened up exciting opportunities for Treg cell therapy in transplantation. In this review, we outline the basic biology of Tregs and discuss recent advances and challenges for the identification, isolation and expansion of these cells for cell therapy. Tregs of thymic origin have been shown to be key regulators of immune responses in mice and humans, preventing autoimmunity, graft-versus-host disease and organ graft rejection in the transplantation setting. To date, a variety of different methods to isolate and expand Tregs ex vivo have been advocated. Although promising, relatively few clinical trials of human Treg cell infusion have been initiated. Many key questions about Treg cell therapy still remain and here we provide an in-depth analysis and highlight the challenges and opportunities for immune intervention with Treg-based therapeutics in clinical transplantation.

Kidney transplantation in the context of renal replacement therapy.

Science.gov (United States)

Pesavento, Todd E

2009-12-01

Kidney transplantation has dramatically evolved from a life-saving yet unproven therapy for patients with renal failure to a mature field that is the preferred treatment for those suffering from ESRD. Patients who receive a transplant experience a 68% lower risk of death compared with those waiting on dialysis for a transplant. This benefit is afforded to all patient subgroups including the elderly (> or =70 yr), and diabetics, who can gain 11 yr of extra life with transplantation. Prolonged transplant wait times result in a higher risk of death but this can be ameliorated with preemptive transplantation. Future challenges will focus on appropriate organ allocation and addressing long-term renal function and comorbid conditions so patients can enjoy the full benefits of transplantation.

Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation is Essential for Functional Regeneration

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Anne Tscherter

2016-09-01

Full Text Available Presently there exists no cure for spinal cord injury. However, transplantation of embryonic tissue into spinal cord lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated spinal cord circuits. We tested the two hypotheses in an in vitro spinal cord lesion model that is based on propagation of activity between two rat organotypic spinal cord slices in culture. Transplantation of dissociated cells from E14 rat spinal cord or forebrain re-established the relay of activity over the lesion site and, thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse forebrain cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated spinal cord circuits. In contrast, transplantation of neurospheres induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated spinal cord circuits.

Human embryonic stem cells: preclinical perspectives

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Sarda Kanchan

2008-01-01

Full Text Available Abstract Human embryonic stem cells (hESCs have been extensively discussed in public and scientific communities for their potential in treating diseases and injuries. However, not much has been achieved in turning them into safe therapeutic agents. The hurdles in transforming hESCs to therapies start right with the way these cells are derived and maintained in the laboratory, and goes up-to clinical complications related to need for patient specific cell lines, gender specific aspects, age of the cells, and several post transplantation uncertainties. The different types of cells derived through directed differentiation of hESC and used successfully in animal disease and injury models are described briefly. This review gives a brief outlook on the present and the future of hESC based therapies, and talks about the technological advances required for a safe transition from laboratory to clinic.

Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration

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Kamil Kruczek

2017-06-01

Full Text Available The loss of cone photoreceptors that mediate daylight vision represents a leading cause of blindness, for which cell replacement by transplantation offers a promising treatment strategy. Here, we characterize cone differentiation in retinas derived from mouse embryonic stem cells (mESCs. Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransduction-related proteins. We establish that stage-specific inhibition of the Notch pathway increases cone cell differentiation, while retinoic acid signaling regulates cone maturation, comparable with their actions in vivo. MESC-derived cones can be isolated in large numbers and transplanted into adult mouse eyes, showing capacity to survive and mature in the subretinal space of Aipl1−/− mice, a model of end-stage retinal degeneration. Together, this work identifies a robust, renewable cell source for cone replacement by purified cell suspension transplantation.

Antibody Desensitization Therapy in Highly Sensitized Lung Transplant Candidates

Science.gov (United States)

Snyder, L. D.; Gray, A. L.; Reynolds, J. M.; Arepally, G. M.; Bedoya, A.; Hartwig, M. G.; Davis, R. D.; Lopes, K. E.; Wegner, W. E.; Chen, D. F.; Palmer, S. M.

2015-01-01

As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multimodal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000–10 000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort. PMID:24666831

Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

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Jennifer E. Bruin

2015-04-01

Full Text Available Human embryonic stem cell (hESC-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

Monitoring embryonic stem cell transplantation into rat corpus cavernosum using optical imaging system

International Nuclear Information System (INIS)

Min, Jung Joon; Moon, Sung Min; Le, Uyenchi N.; Park, Kwang Sung; Lee, Hyun Suk; Song, Ho Cheon; Bom, Hee Seung; Han, Ha Jae

2005-01-01

The conventional method for the analysis of stem cell transplantation depends on postmortem histology. Here, we have sought to demonstrate the feasibility of a longitudinal monitoring of transplanted cell survival in living animals, by employing optical imaging techniques. Mouse embryonic stem cells (ESC) were obtained from American Type Culture Collection (ES-E14TG2a). Mouse ES cells were cultured in the DMEM (Gibco-BRL, Gaithersburg, MD) supplemented with 3.7 g/L sodium bicarbonate, 1 % penicillin and streptomycin, 1.7 mM L-glutamine, 0.1mM β-mercaptoethanol 5 ng/mL mouse leukemia inhibitory factor (LIF), and 15% fetal bovine serum (FBS) with or without a feeder layer and cultured for five days in standard medium plus LIF. ESCs were then transfected (MOI=100) overnight with Ad-CMV-Fluc. Our experimental Sprague-Dawley rats (n=7) were given with different numbers of ESCs 6) expressing Fluc into corpus cavernosum. In cell cultures, firefly luciferase activity correlated linearly with cell numbers from 10 5 to 5x10 6 (r2=0.95). In living animal imaging, imaging signal activity correlated linearly with cell numbers injected from 10 5 to 5x10 6 at each time point (r2=0.62 ∼ 0.98), In all three groups of rats, imaging signal was detected in rat genital area from the 2nd day to the 47th day after cellular injection. Adenovirus mediated transient expression of firefly luciferase reporter gene in ESCs was feasible to monitor cell survival over a month after transplantation. The locations, magnitude, and survival duration of the ESCs were noninvasively monitored with a bioluminescence optical imaging system

Synaptic integration of transplanted interneuron progenitor cells into native cortical networks.

Science.gov (United States)

Howard, MacKenzie A; Baraban, Scott C

2016-08-01

Interneuron-based cell transplantation is a powerful method to modify network function in a variety of neurological disorders, including epilepsy. Whether new interneurons integrate into native neural networks in a subtype-specific manner is not well understood, and the therapeutic mechanisms underlying interneuron-based cell therapy, including the role of synaptic inhibition, are debated. In this study, we tested subtype-specific integration of transplanted interneurons using acute cortical brain slices and visualized patch-clamp recordings to measure excitatory synaptic inputs, intrinsic properties, and inhibitory synaptic outputs. Fluorescently labeled progenitor cells from the embryonic medial ganglionic eminence (MGE) were used for transplantation. At 5 wk after transplantation, MGE-derived parvalbumin-positive (PV+) interneurons received excitatory synaptic inputs, exhibited mature interneuron firing properties, and made functional synaptic inhibitory connections to native pyramidal cells that were comparable to those of native PV+ interneurons. These findings demonstrate that MGE-derived PV+ interneurons functionally integrate into subtype-appropriate physiological niches within host networks following transplantation. Copyright © 2016 the American Physiological Society.

Relationship between Post-kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Complications

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Pourmand, G. R.; Dehghani, S.; Saraji, A.; Khaki, S.; Mortazavi, S. H.; Mehrsai, A.; Sajadi, H.

2012-01-01

Background: Wound healing disorders are probably the most common post-transplantation surgical complications. It is thought that wound healing disturbance occurs due to antiproliferative effects of immunosuppressive drugs. On the other hand, success of transplantation is dependent on immunosuppressive therapies. Antihuman thymocyte globulin (ATG) has been widely used as induction therapy but the impact of this treatment on wound healing is not fully understood. Objective: To investigate wound...

Cyclophosphamide/x-ray: combined mode preparation for transplantation therapy

International Nuclear Information System (INIS)

Meredith, R.; Okunewick, J.; Shadduck, R.; Raikow, R.; Brozovich, B.; Seeman, P.

1979-01-01

Use of total body irradiation (TBI) and/or chemotherapy as a preparation for marrow transplantation in the treatment of leukemia has been only moderately successful in the clinic. Although cyclophosphamide (CY) has shown promise as a marrow ablative agent, leukemia relapses are often found, and optimal therapeutic protocols have not been established. Our transplantation therapy studies of murine leukemia with parental recipients and hybrid donors provide an excellent model for research aimed at improved survival of human transplant patients. Utilizing a murine leukemia induced by a virus, various doses of CY in combination with sub-lethal irradiation were compared to determine the optimal pretreatment for transplantation therapy. Both normal and leukemic mice were engrafted with virus resistant, histocompatible marrow following these preparations, then monitored for survival and long term effects. Leukemic mice were also evaluated for pluripotent as well as myeloid committed stem cells as a measure of the effectiveness of the treatment in elimination of leukemic cells. Leukemic groups were also compared for the percentage and time of leukemia relapse. All CY/X-ray combinations were more effective in elimination of stem cell populations than supralethal TBI alone. However, the best survival was obtained with lethal TBI alone or low dose CY in combination with 550 R

B cell repertoires in HLA-sensitized kidney transplant candidates undergoing desensitization therapy.

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Beausang, John F; Fan, H Christina; Sit, Rene; Hutchins, Maria U; Jirage, Kshama; Curtis, Rachael; Hutchins, Edward; Quake, Stephen R; Yabu, Julie M

2017-01-13

Kidney transplantation is the most effective treatment for end-stage renal disease. Sensitization refers to pre-existing antibodies against human leukocyte antigen (HLA) protein and remains a major barrier to successful transplantation. Despite implementation of desensitization strategies, many candidates fail to respond. Our objective was to determine whether measuring B cell repertoires could differentiate candidates that respond to desensitization therapy. We developed an assay based on high-throughput DNA sequencing of the variable domain of the heavy chain of immunoglobulin genes to measure changes in B cell repertoires in 19 highly HLA-sensitized kidney transplant candidates undergoing desensitization and 7 controls with low to moderate HLA sensitization levels. Responders to desensitization had a decrease of 5% points or greater in cumulated calculated panel reactive antibody (cPRA) levels, and non-responders had no decrease in cPRA. Dominant B cell clones were not observed in highly sensitized candidates, suggesting that the B cells responsible for sensitization are either not present in peripheral blood or present at comparable levels to other circulating B cells. Candidates that responded to desensitization therapy had pre-treatment repertoires composed of a larger fraction of class-switched (IgG and IgA) isotypes compared to non-responding candidates. After B cell depleting therapy, the proportion of switched isotypes increased and the mutation frequencies of the remaining non-switched isotypes (IgM and IgD) increased in both responders and non-responders, perhaps representing a shift in the repertoire towards memory B cells or plasmablasts. Conversely, after transplantation, non-switched isotypes with fewer mutations increased, suggesting a shift in the repertoire towards naïve B cells. Relative abundance of different B cell isotypes is strongly perturbed by desensitization therapy and transplantation, potentially reflecting changes in the relative

Embryonic vaccines against cancer: an early history.

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Brewer, Bradley G; Mitchell, Robert A; Harandi, Amir; Eaton, John W

2009-06-01

Almost 100 years have passed since the seminal observations of Schöne showing that vaccination of animals with fetal tissue would prevent the growth of transplantable tumors. Many subsequent reports have affirmed the general idea that immunologic rejection of transplantable tumors, as well as prevention of carcinogenesis, may be affected by vaccination with embryonic/fetal material. Following a decade of intense research on this phenomenon during approximately 1964-1974, interest appears to have waned. This earlier experimental work may be particularly pertinent in view of the rising interest in so-called cancer stem cells. We believe that further work - perhaps involving the use of embryonic stem cells as immunogens - is warranted and that the results reviewed herein support the concept that vaccination against the appearance of cancers of all kinds is a real possibility.

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

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Kim, Young; Stahl, Christopher C; Makramalla, Abouelmagd; Olowokure, Olugbenga O; Ristagno, Ross L; Dhar, Vikrom K; Schoech, Michael R; Chadalavada, Seetharam; Latif, Tahir; Kharofa, Jordan; Bari, Khurram; Shah, Shimul A

2017-12-01

Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for

Renal Infarction during Anticoagulant Therapy after Living Donor Liver Transplantation

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Shinji Onda

2018-04-01

Full Text Available Introduction: Liver transplant recipients are at risk for complications of vascular thrombosis. The reconstructed hepatic artery and portal vein thrombosis potentially result in hepatic failure and graft loss. Renal infarction is a rare clinical condition, but in severe cases, it may lead to renal failure. We herein report a case of renal infarction after living donor liver transplantation (LDLT during anticoagulant therapy. Case Presentation: A 60-year-old woman with end-stage liver disease due to primary biliary cholangitis underwent LDLT with splenectomy. Postoperatively, tacrolimus, mycophenolate mofetil, and steroid were used for initial immunosuppression therapy. On postoperative day (POD 5, enhanced computed tomography (CT revealed splenic vein thrombosis, and anticoagulant therapy with heparin followed by warfarin was given. Follow-up enhanced CT on POD 20 incidentally demonstrated right renal infarction. The patient’s renal function was unchanged and the arterial flow was good, and the splenic vein thrombosis resolved. At 4 months postoperatively, warfarin was discontinued, but she developed recurrent splenic vein thrombosis 11 months later, and warfarin was resumed. As of 40 months after transplantation, she discontinued warfarin and remains well without recurrence of splenic vein thrombosis or renal infarction. Conclusion: Renal infarction is a rare complication of LDLT. In this case, renal infarction was incidentally diagnosed during anticoagulant therapy and was successfully treated.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

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Preeti Chhabra

2011-01-01

Full Text Available Clinical islet transplantation is a -cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the -cells regenerative capacity of stem cells.

Primate Primordial Germ Cells Acquire Transplantation Potential by Carnegie Stage 23.

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Clark, Amander T; Gkountela, Sofia; Chen, Di; Liu, Wanlu; Sosa, Enrique; Sukhwani, Meena; Hennebold, Jon D; Orwig, Kyle E

2017-07-11

Primordial germ cells (PGCs) are the earliest embryonic progenitors in the germline. Correct formation of PGCs is critical to reproductive health as an adult. Recent work has shown that primate PGCs can be differentiated from pluripotent stem cells; however, a bioassay that supports their identity as transplantable germ cells has not been reported. Here, we adopted a xenotransplantation assay by transplanting single-cell suspensions of human and nonhuman primate embryonic Macaca mulatta (rhesus macaque) testes containing PGCs into the seminiferous tubules of adult busulfan-treated nude mice. We discovered that both human and nonhuman primate embryonic testis are xenotransplantable, generating colonies while not generating tumors. Taken together, this work provides two critical references (molecular and functional) for defining transplantable primate PGCs. These results provide a blueprint for differentiating pluripotent stem cells to transplantable PGC-like cells in a species that is amenable to transplantation and fertility studies. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Genetic modification of cells for transplantation.

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Lai, Yi; Drobinskaya, Irina; Kolossov, Eugen; Chen, Chunguang; Linn, Thomas

2008-01-14

Progress in gene therapy has produced promising results that translate experimental research into clinical treatment. Gene modification has been extensively employed in cell transplantation. The main barrier is an effective gene delivery system. Several viral vectors were utilized in end-stage differentiated cells. Recently, successful applications were described with adenovirus-associated vectors. As an alternative, embryonic stem cell- and stem cell-like systems were established for generation of tissue-specified gene-modified cells. Owing to the feasibility for genetic manipulations and the self-renewing potency of these cells they can be used in a way enabling large-scale in vitro production. This approach offers the establishment of in vitro cell culture systems that will deliver sufficient amounts of highly purified, immunoautologous cells suitable for application in regenerative medicine. In this review, the current technology of gene delivery systems to cells is recapitulated and the latest developments for cell transplantation are discussed.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

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Chhabra, Preeti; Brayman, Kenneth L.

2011-01-01

Clinical islet transplantation is a β-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the β-cells regenerative capacity of stem cells. PMID:22046502

Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy

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Ching-Yao Yang

2016-06-01

Conclusion: When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation.

The Power and the Promise of Cell Reprogramming: Personalized Autologous Body Organ and Cell Transplantation

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Ana Belen Alvarez Palomo

2014-04-01

Full Text Available Reprogramming somatic cells to induced pluripotent stem cells (iPSCs or direct reprogramming to desired cell types are powerful and new in vitro methods for the study of human disease, cell replacement therapy, and drug development. Both methods to reprogram cells are unconstrained by the ethical and social questions raised by embryonic stem cells. iPSC technology promises to enable personalized autologous cell therapy and has the potential to revolutionize cell replacement therapy and regenerative medicine. Potential applications of iPSC technology are rapidly increasing in ambition from discrete cell replacement applications to the iPSC assisted bioengineering of body organs for personalized autologous body organ transplant. Recent work has demonstrated that the generation of organs from iPSCs is a future possibility. The development of embryonic-like organ structures bioengineered from iPSCs has been achieved, such as an early brain structure (cerebral organoids, bone, optic vesicle-like structures (eye, cardiac muscle tissue (heart, primitive pancreas islet cells, a tooth-like structure (teeth, and functional liver buds (liver. Thus, iPSC technology offers, in the future, the powerful and unique possibility to make body organs for transplantation removing the need for organ donation and immune suppressing drugs. Whilst it is clear that iPSCs are rapidly becoming the lead cell type for research into cell replacement therapy and body organ transplantation strategies in humans, it is not known whether (1 such transplants will stimulate host immune responses; and (2 whether this technology will be capable of the bioengineering of a complete and fully functional human organ. This review will not focus on reprogramming to iPSCs, of which a plethora of reviews can be found, but instead focus on the latest developments in direct reprogramming of cells, the bioengineering of body organs from iPSCs, and an analysis of the immune response induced by i

A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

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Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

2014-04-17

Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

Cell-Based Therapy

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Masaaki Kitada

2012-01-01

Full Text Available Cell transplantation is a strategy with great potential for the treatment of Parkinson's disease, and many types of stem cells, including neural stem cells and embryonic stem cells, are considered candidates for transplantation therapy. Mesenchymal stem cells are a great therapeutic cell source because they are easy accessible and can be expanded from patients or donor mesenchymal tissues without posing serious ethical and technical problems. They have trophic effects for protecting damaged tissues as well as differentiation ability to generate a broad spectrum of cells, including dopamine neurons, which contribute to the replenishment of lost cells in Parkinson's disease. This paper focuses mainly on the potential of mesenchymal stem cells as a therapeutic cell source and discusses their potential clinical application in Parkinson's disease.

Bio-engineering inslulin-secreting cells from embryonic stem cells: a review of progress.

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Roche, E; Sepulcre, M P; Enseñat-Waser, R; Maestre, I; Reig, J A; Soria, B

2003-07-01

According to the Edmonton protocol, human islet transplantation can result in insulin independency for periods longer than 3 years. However, this therapy for type 1 diabetes is limited by the scarcity of cadaveric donors. Owing to the ability of embryonic stem cells to expand in vitro and differentiate into a variety of cell types, research has focused on ways to manipulate these cells to overcome this problem. It has been demonstrated that mouse embryonic stem cells can differentiate into insulin-containing cells, restoring normoglycaemia in diabetic mice. To this end, mouse embryonic stem cells were transfected with a DNA construct that provides resistance to neomycin under the control of the regulatory regions of the human insulin gene. However, this protocol has a very low efficiency, needing improvements for this technology to be transferred to human stem cells. Optimum protocols will be instrumental in the production of an unlimited source of cells that synthesise, store and release insulin in a physiological manner. The review focuses on the alternative source of tissue offered by embryonic stem cells for regenerative medicine in diabetes and some key points that should be considered in order for a definitive protocol for in vitro differentiation to be established.

Labeling human embryonic stem-cell-derived cardiomyocytes for tracking with MR imaging

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Castaneda, Rosalinda T.; Daldrup-Link, Heike [Lucile Packard Children' s Hospital, Stanford School of Medicine, Pediatric Radiology, Stanford, CA (United States); Boddington, Sophie; Wendland, Mike; Mandrussow, Lydia [University of California, Department of Radiology and Biomedical Imaging, UCSF Medical Center, San Francisco, CA (United States); Henning, Tobias D. [University Hospital of Cologne, Department of Radiology and Neuroradiology, Cologne (Germany); Liu, Siyuan [National Institutes of Health, Language Section, Voice, Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, Bethesda, MD (United States)

2011-11-15

Human embryonic stem cells (hESC) can generate cardiomyocytes (CM), which offer promising treatments for cardiomyopathies in children. However, challenges for clinical translation result from loss of transplanted cell from target sites and high cell death. An imaging technique that noninvasively and repetitively monitors transplanted hESC-CM could guide improvements in transplantation techniques and advance therapies. To develop a clinically applicable labeling technique for hESC-CM with FDA-approved superparamagnetic iron oxide nanoparticles (SPIO) by examining labeling before and after CM differentiation. Triplicates of hESC were labeled by simple incubation with 50 {mu}g/ml of ferumoxides before or after differentiation into CM, then imaged on a 7T MR scanner using a T2-weighted multi-echo spin-echo sequence. Viability, iron uptake and T2-relaxation times were compared between groups using t-tests. hESC-CM labeled before differentiation demonstrated significant MR effects, iron uptake and preserved function. hESC-CM labeled after differentiation showed no significant iron uptake or change in MR signal (P < 0.05). Morphology, differentiation and viability were consistent between experimental groups. hESC-CM should be labeled prior to CM differentiation to achieve a significant MR signal. This technique permits monitoring delivery and engraftment of hESC-CM for potential advancements of stem cell-based therapies in the reconstitution of damaged myocardium. (orig.)

Labeling human embryonic stem-cell-derived cardiomyocytes for tracking with MR imaging

International Nuclear Information System (INIS)

Castaneda, Rosalinda T.; Daldrup-Link, Heike; Boddington, Sophie; Wendland, Mike; Mandrussow, Lydia; Henning, Tobias D.; Liu, Siyuan

2011-01-01

Human embryonic stem cells (hESC) can generate cardiomyocytes (CM), which offer promising treatments for cardiomyopathies in children. However, challenges for clinical translation result from loss of transplanted cell from target sites and high cell death. An imaging technique that noninvasively and repetitively monitors transplanted hESC-CM could guide improvements in transplantation techniques and advance therapies. To develop a clinically applicable labeling technique for hESC-CM with FDA-approved superparamagnetic iron oxide nanoparticles (SPIO) by examining labeling before and after CM differentiation. Triplicates of hESC were labeled by simple incubation with 50 μg/ml of ferumoxides before or after differentiation into CM, then imaged on a 7T MR scanner using a T2-weighted multi-echo spin-echo sequence. Viability, iron uptake and T2-relaxation times were compared between groups using t-tests. hESC-CM labeled before differentiation demonstrated significant MR effects, iron uptake and preserved function. hESC-CM labeled after differentiation showed no significant iron uptake or change in MR signal (P < 0.05). Morphology, differentiation and viability were consistent between experimental groups. hESC-CM should be labeled prior to CM differentiation to achieve a significant MR signal. This technique permits monitoring delivery and engraftment of hESC-CM for potential advancements of stem cell-based therapies in the reconstitution of damaged myocardium. (orig.)

Amniotic membrane transplantation ineffective as additional therapy in patients with aggressive Mooren's ulcer.

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Schallenberg, Maurice; Westekemper, Henrike; Steuhl, Klaus-Peter; Meller, Daniel

2013-12-17

Mooren's ulcer is a severe ulcerative inflammation of the cornea. The exact pathogenesis remains unclear. Therefore many therapies of Mooren's ulcer are recommended in literature. To shed more light on the ongoing question of optimal treatment of severe progressive Mooren's ulcer, we here report on a retrospective case series of patients treated with systemic immunosuppressive therapy and additional amniotic membrane transplantation. Medical records from seven patients (eleven eyes), 4 male and 3 female, with severe progressive Mooren's ulcer were analysed retrospectively. The mean follow up was 88.4 ± 80.8 months (range 12-232 month). A HLA-typing was performed in all patients. A systemic immunosuppressive therapy was administered in all patients. The amniotic membrane was transplanted after the base of the ulcer was resected. Multiple amniotic membrane transplantations were necessary in six patients. The visual outcome of all patients was poor. No patient achieved a visual acuity better than 20/630 Snellen chart. Five patients were positive for HLA-DQ2 and four patients were positive for HLA-DR17(3). The aggressive and highly inflammatory form of Mooren's ulcer is difficult to treat and the progression of the disease is hard to influence positively even under systemic immunosuppressive therapy. Therefore, the main intention of therapy is to achieve a stable epithelialized corneal surface without the risk of perforation. Amniotic membrane transplantation is not able to cure severe forms of Mooren's ulcer. However it supports the immunosuppressive therapy in acute situations as in critical corneal thinning.

The future of replacement and restorative therapies: from organ transplantation to regenerative medicine.

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Daar, A S

2013-01-01

As we continue to have severe shortages of organs for transplantation, we need to consider alternatives for the future. The most likely to make a real difference in the long term is regenerative medicine (RM), a field that has emerged from the conjunction of stem cell biology and cell therapies; gene therapy; biomaterials and tissue engineering; and organ transplantation. Transplantation and RM share the same essential goal: to replace or restore organ function. Herein I briefly review some major breakthroughs of RM that are relevant to the future of organ transplantation, with a focus on the needs of people in the developing world. A definition of RM is provided and the ethical, legal, and social issues are briefly highlighted. In conclusion, I provide a projection of what the future may be for RM. Copyright © 2013 Elsevier Inc. All rights reserved.

Nursing care of patients receiving interventional therapy for hepatic artery stenosis after liver transplantation

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Wei Lin; Liu Shiguang

2009-01-01

Objective: To discuss the perioperative nursing care of patients who is going to receive interventional therapy for hepatic artery stenosis after liver transplantation and to provide useful reference for reducing surgery-related complication and for improving the prognosis of patients. Methods: Based on the patient's condition and operative requirement,we provided effective nursing care for 20 patients who were admitted to receive the interventional therapy for hepatic artery stenosis after liver transplantation. The nursing care included preoperative preparation,postoperative nursing and medical guidance at the time of discharge. Results: Interventional therapy was successfully performed in all 20 cases, and no hemorrhagic tendency or acute thrombosis occurred. Marked symptomatic improvement was obtained in all patients. Conclusion: The interventional therapy is an effective treatment for hepatic artery stenosis after liver transplantation. Intensive perioperative nursing care can well prevent the occurrence of surgery-related complications and can surely improve the therapeutic results. (authors)

Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes.

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Garrouste, Cyril; Anglicheau, Dany; Kamar, Nassim; Bachelier, Claire; Rivalan, Joseph; Pereira, Bruno; Caillard, Sophie; Aniort, Julien; Gatault, Philippe; Soubrier, Martin; Sayegh, Johnny; Colosio, Charlotte; Buisson, Anthony; Thervet, Eric; Bouvier, Nicolas; Heng, Anne Elisabeth

2016-10-01

Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1).Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12-55] and 40 [21-53] mL/min/1.73 m, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06).Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

Side Effects of Transplant Immunosuppressive Therapy in Post Renal Transplant Recipients, Mazandaran, Northern Iran

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Abazar Akbarzadeh Pasha

2017-04-01

Full Text Available Background Post-kidney transplant survival relies on patient adherence to the intake of immunosuppressive medication. This study was performed to investigate complications associated with immunosuppressive therapy in renal transplantation. Methods This cross-sectional study was conducted on 188 transplanted patients in Shahid Beheshti hospital of Babol in 2013. Check list and demographic questionnaire for data collecting were used. Then the data using were analyzed in SPSS.18 software by using chi-square test. Results A total of 188 transplanted patients, 115 (61.2% was male and mean age was 12.9 ± 42.9 years. 181 (96.3% of the subjects had at least one complication. The most common complication in 142 cases (75.5% was “excessive hair growth” and after this complication “increased blood sugar” had higher frequency and 119 (63.3% had this complication. Severe form of gingival overgrowth in women was significantly that more than men (22 (30.1, 14 (12.2, P = 0.004, and the other side effect was not significant difference between men and women or different age groups (P > 0.05 Conclusions Finding show that nearly all transplanted recipients suffered from one complication which need to recognize, control and treatment. It suggested that period visiting for early diagnosis and education to patient was recommend.

In vitro generation of three-dimensional substrate-adherent embryonic stem cell-derived neural aggregates for application in animal models of neurological disorders.

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Hargus, Gunnar; Cui, Yi-Fang; Dihné, Marcel; Bernreuther, Christian; Schachner, Melitta

2012-05-01

In vitro-differentiated embryonic stem (ES) cells comprise a useful source for cell replacement therapy, but the efficiency and safety of a translational approach are highly dependent on optimized protocols for directed differentiation of ES cells into the desired cell types in vitro. Furthermore, the transplantation of three-dimensional ES cell-derived structures instead of a single-cell suspension may improve graft survival and function by providing a beneficial microenvironment for implanted cells. To this end, we have developed a new method to efficiently differentiate mouse ES cells into neural aggregates that consist predominantly (>90%) of postmitotic neurons, neural progenitor cells, and radial glia-like cells. When transplanted into the excitotoxically lesioned striatum of adult mice, these substrate-adherent embryonic stem cell-derived neural aggregates (SENAs) showed significant advantages over transplanted single-cell suspensions of ES cell-derived neural cells, including improved survival of GABAergic neurons, increased cell migration, and significantly decreased risk of teratoma formation. Furthermore, SENAs mediated functional improvement after transplantation into animal models of Parkinson's disease and spinal cord injury. This unit describes in detail how SENAs are efficiently derived from mouse ES cells in vitro and how SENAs are isolated for transplantation. Furthermore, methods are presented for successful implantation of SENAs into animal models of Huntington's disease, Parkinson's disease, and spinal cord injury to study the effects of stem cell-derived neural aggregates in a disease context in vivo.

Invasive fungal infections and antifungal therapies in solid organ transplant recipients.

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Gabardi, Steven; Kubiak, David W; Chandraker, Anil K; Tullius, Stefan G

2007-12-01

This manuscript will review the risk factors, prevalence, clinical presentation, and management of invasive fungal infections (IFIs) in solid organ transplant (SOT) recipients. Primary literature was obtained via MEDLINE (1966-April 2007) and EMBASE. Abstracts were obtained from scientific meetings or pharmaceutical manufacturers and included in the analysis. All studies and abstracts evaluating IFIs and/or antifungal therapies, with a primary focus on solid organ transplantation, were considered for inclusion. English-language literature was selected for inclusion, but was limited to those consisting of human subjects. Infectious complications following SOT are common. IFIs are associated with high morbidity and mortality rates in this patient population. Determining the best course of therapy is difficult due to the limited availability of data in SOT recipients. Well-designed clinical studies are infrequent and much of the available information is often based on case-reports or retrospective analyses. Transplant practitioners must remain aware of their therapeutic options and the advantages and disadvantages associated with the available treatment alternatives.

Therapeutic approaches for treating hemophilia A using embryonic stem cells.

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Kasuda, Shogo; Tatsumi, Kohei; Sakurai, Yoshihiko; Shima, Midori; Hatake, Katsuhiko

2016-06-01

Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl4)-pretreated wild-type mice, and CCl4-pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Transplantation Tolerance Induction: Cell Therapies and their Mechanisms

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Joseph R Scalea

2016-03-01

Full Text Available Cell based therapies have been studied extensively in the context of transplantation tolerance induction. The most successful protocols have relied on transfusion of bone marrow prior to the transplantation of a renal allograft. However, it is not clear that stem cells found in bone marrow are required in order to render a transplant candidate immunologically tolerant. Accordingly, mesenchymal stem cells, regulatory myeloid cells, T regulatory cells, and other cell types, are being tested as possible routes to tolerance induction, in the absence of donor derived stem cells. Early data with each of these cell types have been encouraging. However, the induction regimen capable of achieving consistent tolerance, whilst avoiding unwanted sided effects, and which is scalable to the human patient, has yet to be identified. Here we present the status of investigations of various tolerogenic cell types and the mechanistic rationale for their use in in tolerance induction protocols.

Stem cell and gene therapies for diabetes mellitus.

Science.gov (United States)

Calne, Roy Y; Gan, Shu Uin; Lee, Kok Onn

2010-03-01

In this Perspectives article, we comment on the progress in experimental stem cell and gene therapies that might one day become a clinical reality for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Finally, gene therapy shows some promise for the generation of insulin-producing cells. Here, we discuss two of the most frequently used approaches: in vitro gene delivery into cells which are then transplanted into the recipient and direct delivery of genes in vivo.

Human and murine very small embryonic-like cells represent multipotent tissue progenitors, in vitro and in vivo.

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Havens, Aaron M; Sun, Hongli; Shiozawa, Yusuke; Jung, Younghun; Wang, Jingcheng; Mishra, Anjali; Jiang, Yajuan; O'Neill, David W; Krebsbach, Paul H; Rodgerson, Denis O; Taichman, Russell S

2014-04-01

The purpose of this study was to determine the lineage progression of human and murine very small embryonic-like (HuVSEL or MuVSEL) cells in vitro and in vivo. In vitro, HuVSEL and MuVSEL cells differentiated into cells of all three embryonic germ layers. HuVSEL cells produced robust mineralized tissue of human origin compared with controls in calvarial defects. Immunohistochemistry demonstrated that the HuVSEL cells gave rise to neurons, adipocytes, chondrocytes, and osteoblasts within the calvarial defects. MuVSEL cells were also able to differentiate into similar lineages. First round serial transplants of MuVSEL cells into irradiated osseous sites demonstrated that ∼60% of the cells maintained their VSEL cell phenotype while other cells differentiated into multiple tissues at 3 months. Secondary transplants did not identify donor VSEL cells, suggesting limited self renewal but did demonstrate VSEL cell derivatives in situ for up to 1 year. At no point were teratomas identified. These studies show that VSEL cells produce multiple cellular structures in vivo and in vitro and lay the foundation for future cell-based regenerative therapies for osseous, neural, and connective tissue disorders.

Primary prevention of skin dysplasia in renal transplant recipients with photodynamic therapy

DEFF Research Database (Denmark)

Togsverd-Bo, K; Omland, S H; Wulf, H C

2015-01-01

Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK...

Medical nutrition therapy in chronic kidney disease; from dialysis to transplant: A case report

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Gabriela Leal-Escobar

2016-01-01

Full Text Available Chronic kidney disease has direct implications in nutritional status, causing anorexia and muscular catabolism. These situations are frequent in kidney renal replacement therapy in which nutritional disorders and inflammatory mechanisms associated with therapy often lead to the development of protein-energy wasting. Nutrition therapy has shown an adequate therapeutic strategy to prevent and treat metabolic alterations, reducing surgical and nutritional complication risks in kidney transplantation patients. The current case reports nutritional intervention on a continuous ambulatory peritoneal dialysis patient who was subsequently prescribed to automatic peritoneal dialysis and, finally, kidney transplant from a living donor.

Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

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Gabardi, Steven; Catella, Jennifer; Martin, Spencer T; Perrone, Ronald; Chandraker, Anil; Magee, Colm C; McDevitt-Potter, Lisa M

2011-09-01

To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2

Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

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Ruchi Sharma

2010-01-01

Full Text Available The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

Storing live embryonic and adult human cartilage grafts for transplantation using a joint simulating device.

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Cohen, I; Robinson, D; Cohen, N; Nevo, Z

2000-11-01

Cartilage transplantation as a means to replace damaged articular surfaces is of interest. A major obstacle is the long-term preservation of cartilage grafts. The commonly used technique of freezing the grafts inevitably leads to cellular death. The current study compares the technique to an innovative approach using a pulsed-pressure perfusion system termed a joint simulating device (JSD), intended to simulate intra-articular mechanical forces. Human articular cartilage explants were harvested from both embryonic epiphyseal tissue and femoral heads of elderly women (over 70 years of age) undergoing a partial joint replacement (hemi-arthroplasty) and were divided in two groups: half of the samples were incubated in the JSD while the remaining half were grown in static culture within tissue culture plates. After 10 days all samples were evaluated for: (a) cell vitality as assessed by image analysis and XTT assay; (b) biosynthetic activity as expressed by radioactive sulfate incorporation into glycosaminoglycans (GAG's); and (c) proteoglycan content as assessed by alcian blue staining intensity. A 10-fold increase in sulfate incorporation in samples held in the JSD compared to the static culture group was observed in embryonic cartilage. In adult cartilage culture in the JSD elevated sulfate incorporation by threefold as compared to static culture. Central necrosis was observed in specimens grown in the static culture plates, while it did not occur in the samples held in the JSD. Cell vitality as assessed by XTT assay was significantly better in the JSD group as compared to static culture. The difference was more pronounced in the embryonic specimens as compared to adult cartilage. The specimens cultured within the JSD retained proteoglycans significantly better than those cultured in static culture. Maintenance of cartilage specimens in a JSD was highly effective in keeping the vitality of cartilage explants in vitro over a 10-day period. A possible future

Renal transplantation across the donor-specific antibody barrier: Graft outcome and cancer risk after desensitization therapy.

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Yang, Ching-Yao; Lee, Chih-Yuan; Yeh, Chi-Chuan; Tsai, Meng-Kun

2016-06-01

Desensitization regimens including use of intravenous immune globulin and rituximab have been reported to overcome renal transplant hyperacute rejection. A retrospective case-control study was performed to assess the results and complications of renal transplantation with desensitization therapy for donor-specific antibody (DSA) in a transplant center in Asia, where donor exchange was usually not allowed. Between January 2007 and December 2013, 22 patients with DSA received live-donor renal transplantation after desensitization (DSA group). During the same period, the DSA group was compared to the NSA group (152 renal transplants) who had no specific antibody to the donors (66 from deceased donors and 86 from living relatives). Rejection, renal function, graft and patient survival rates, infection, and cancer incidence were reviewed and analyzed from medical records. The DSA group (46.8%) had significantly higher acute rejection rates than the NSA group (13.7%) at the 1-year follow-up. The estimated renal function, 5-year graft, and patient survival rates were comparable between the groups. The DSA group (19.6%) had significantly higher 5-year de novo cancer incidence than the NSA group (8.5%; p = 0.028); three patients of the DSA group developed urothelial carcinoma 17.0 ± 3.0 months after transplantation. By using stepwise Cox regression analysis, desensitization therapy was identified as the sole independent risk factor for post-transplant urothelial carcinoma. When compared to renal transplantation without DSA, desensitization therapy for DSA resulted in equivalent renal transplant outcome but potentially increased risk of urothelial carcinoma after transplantation. Copyright © 2015. Published by Elsevier B.V.

High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma

NARCIS (Netherlands)

Schouten, IC; Raemaekers, JJM; Kluin-Nelemans, HC; vanKamp, H; Mellink, WAM; vantVeer, MB

1996-01-01

Purpose: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site

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Andrew R. Pepper

2017-06-01

Full Text Available Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of “healthy” human donor pancreata restricts the broader application of this effective curative therapy. “β-Like” cells derived from human embryonic stem cells (hESC, with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.

Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells.

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Li, Yao; Chan, Lawrence; Nguyen, Huy V; Tsang, Stephen H

2016-01-01

Interest in generating human induced pluripotent stem (iPS) cells for stem cell modeling of diseases has overtaken that of patient-specific human embryonic stem cells due to the ethical, technical, and political concerns associated with the latter. In ophthalmology, researchers are currently using iPS cells to explore various applications, including: (1) modeling of retinal diseases using patient-specific iPS cells; (2) autologous transplantation of differentiated retinal cells that undergo gene correction at the iPS cell stage via gene editing tools (e.g., CRISPR/Cas9, TALENs and ZFNs); and (3) autologous transplantation of patient-specific iPS-derived retinal cells treated with gene therapy. In this review, we will discuss the uses of patient-specific iPS cells for differentiating into retinal pigment epithelium (RPE) cells, uncovering disease pathophysiology, and developing new treatments such as gene therapy and cell replacement therapy via autologous transplantation.

Comparison of Teratoma Formation between Embryonic Stem Cells and Parthenogenetic Embryonic Stem Cells by Molecular Imaging

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Hongyan Tao

2018-01-01

Full Text Available With their properties of self-renewal and differentiation, embryonic stem (ES cells hold great promises for regenerative therapy. However, teratoma formation and ethical concerns of ES cells may restrict their potential clinical applications. Currently, parthenogenetic embryonic stem (pES cells have attracted the interest of researchers for its self-renewing and pluripotent differentiation while eliciting less ethic concerns. In this study, we established a model with ES and pES cells both stably transfected with a double-fusion reporter gene containing renilla luciferase (Rluc and red fluorescent protein (RFP to analyze the mechanisms of teratoma formation. Transgenic Vegfr2-luc mouse, which expresses firefly luciferase (Fluc under the promoter of vascular endothelial growth factor receptor 2 (Vegfr2-luc, was used to trace the growth of new blood vessel recruited by transplanted cells. Bioluminescence imaging (BLI of Rluc/Fluc provides an effective tool in estimating the growth and angiogenesis of teratoma in vivo. We found that the tumorigenesis and angiogenesis capacity of ES cells were higher than those of pES cells, in which VEGF/VEGFR2 signal pathway plays an important role. In conclusion, pES cells have the decreased potential of teratoma formation but meanwhile have similar differentiating capacity compared with ES cells. These data demonstrate that pES cells provide an alternative source for ES cells with the risk reduction of teratoma formation and without ethical controversy.

Cardiac transplantation after bridged therapy with continuous flow left ventricular assist devices.

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Deo, Salil V; Sung, Kiick; Daly, Richard C; Shah, Ishan K; Altarabsheh, Salah E; Stulak, John M; Joyce, Lyle D; Boilson, Barry A; Kushwaha, Sudhir S; Park, Soon J

2014-03-01

Cardiac transplantation is an effective surgical therapy for end-stage heart failure. Patients (pts) may need to be bridged with a continuous flow left ventricular assist device (CF-LVAD) while on the transplant list as logistic factors like organ availability are unknown. Cardiac transplantation post-LVAD can be a surgically challenging procedure and outcome in these pts is perceived to be poorer based on experience with earlier generation pulsatile flow pumps. Data from a single institution comparing these pts with those undergoing direct transplantation in the present era of continuous flow device therapy are limited. Evaluate results of cardiac transplantation in pts bridged with a CF-LVAD (BTx) and compare outcomes with pts undergoing direct transplantation (Tx) in a single institution. From June 2007 till January 2012, 106 pts underwent cardiac transplantation. Among these, 37 (35%) pts (51±11 years; 85% male) were bridged with a CF-LVAD (BTx), while 70 (65%) comprised the Tx group (53±12 years; 72% males). The median duration of LVAD support was 227 (153,327) days. During the period of LVAD support, 10/37 (27%) pts were upgraded to status 1A and all were successfully transplanted. Median hospital stay in the BTx (14 days) was slightly longer than the Tx group (12 days) but not statistically significant (p=0.21). In-hospital mortality in the BTx (5%) and Tx (1%) were comparable (p=0.25). Estimated late survival in the BTx cohort was 94±7, 90±10 and 83±16% at the end of one, two and three years, respectively which was comparable to 97±4%, 93±6% and 89±9% for the Tx group (p=0.50). Cardiac transplantation after LVAD implant can be performed with excellent results. Patients can be supported on the left ventricular assist device even for periods close to a year with good outcome after cardiac transplantation. Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand

Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease.

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Shroff, Geeta

2016-12-13

BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.

Stem cell therapy for retinal diseases

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Garcia, José Mauricio; Mendonça, Luisa; Brant, Rodrigo; Abud, Murilo; Regatieri, Caio; Diniz, Bruno

2015-01-01

In this review, we discuss about current knowledge about stem cell (SC) therapy in the treatment of retinal degeneration. Both human embryonic stem cell and induced pluripotent stem cell has been growth in culture for a long time, and started to be explored in the treatment of blinding conditions. The Food and Drug Administration, recently, has granted clinical trials using SC retinal therapy to treat complex disorders, as Stargardt’s dystrophy, and patients with geographic atrophy, providing good outcomes. This study’s intent is to overview the critical regeneration of the subretinal anatomy through retinal pigment epithelium transplantation, with the goal of reestablish important pathways from the retina to the occipital cortex of the brain, as well as the differentiation from pluripotent quiescent SC to adult retina, and its relationship with a primary retinal injury, different techniques of transplantation, management of immune rejection and tumorigenicity, its potential application in improving patients’ vision, and, finally, approaching future directions and challenges for the treatment of several conditions. PMID:25621115

Reversal of Type 1 Diabetes in Mice by Brown Adipose Tissue Transplant

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Gunawardana, Subhadra C.; Piston, David W.

2012-01-01

Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized glucose tolerance, reduced tissue inflammation, and reversal of clinical diabetes markers such as polyuria, polydipsia, and polyphagia. These effects are independent of insulin but correlate with recovery of the animals’ white adipose tissue. BAT transplants lead to significant increases in adiponectin and leptin, but with levels that are static and not responsive to glucose. Pharmacological blockade of the insulin receptor in BAT transplant mice leads to impaired glucose tolerance, similar to what is seen in nondiabetic animals, indicating that insulin receptor activity plays a role in the reversal of diabetes. One possible candidate for activating the insulin receptor is IGF-1, whose levels are also significantly elevated in BAT transplant mice. Thus, we propose that the combined action of multiple adipokines establishes a new equilibrium in the animal that allows for chronic glycemic control without insulin. PMID:22315305

High-dose therapy and autologous transplantation for lymphoma: the Peter MacCallum Cancer institute experience

International Nuclear Information System (INIS)

Dowling, A.J.; Prince, H.M.; Wolf, M.; Januszewicz, H.; Seymour, J.F.; Gates, P.; Wirth, A.; Juneja, S.; Smith, J.G.

2001-01-01

High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986. To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986-95). A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS). Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at transplant (P= 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%).There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time (P =0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time. HDT with autologous transplantation achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further

Music Therapy for Symptom Management After Autologous Stem Cell Transplantation: Results From a Randomized Study.

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Bates, Debbie; Bolwell, Brian; Majhail, Navneet S; Rybicki, Lisa; Yurch, Melissa; Abounader, Donna; Kohuth, Joseph; Jarancik, Shannon; Koniarczyk, Heather; McLellan, Linda; Dabney, Jane; Lawrence, Christine; Gallagher, Lisa; Kalaycio, Matt; Sobecks, Ronald; Dean, Robert; Hill, Brian; Pohlman, Brad; Hamilton, Betty K; Gerds, Aaron T; Jagadeesh, Deepa; Liu, Hien D

2017-09-01

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is frequently performed in patients with hematologic malignancies. ASCT can result in significant nausea, pain, and discomfort. Supportive care has improved, and pharmacologic therapies are frequently used, but with limitations. Music has been demonstrated to improve nausea and pain in patients undergoing chemotherapy, but little data are available regarding the effects of music therapy in the transplantation setting. In a prospective study, patients with lymphoma or multiple myeloma undergoing ASCT were randomized to receive either interactive music therapy with a board-certified music therapist or no music therapy. The music therapy arm received 2 music therapy sessions on days +1 and +5. Primary outcomes were perception of pain and nausea measured on a visual analog scale. Secondary outcomes were narcotic pain medication use from day -1 to day +5 and impact of ASCT on patient mood as assessed by Profile of Mood States (POMS) on day +5. Eighty-two patients were enrolled, with 37 in the music therapy arm and 45 in the no music therapy arm. Patients who received MT had slightly increased nausea by day +7 compared with the no music therapy patients. The music therapy and no music therapy patients had similar pain scores; however, the patients who received music therapy used significantly less narcotic pain medication (median, 24 mg versus 73 mg; P = .038). Music therapy may be a viable nonpharmacologic method of pain management for patients undergoing ASCT; the music therapy patients required significantly fewer morphine equivalent doses compared with the no music therapy patients. Additional research is needed to better understand the effects of music therapy on patient-perceived symptoms, such as pain and nausea. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Differentiation and functional incorporation of embryonic stem cell-derived GABAergic interneurons in the dentate gyrus of mice with temporal lobe epilepsy.

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Maisano, Xu; Litvina, Elizabeth; Tagliatela, Stephanie; Aaron, Gloster B; Grabel, Laura B; Naegele, Janice R

2012-01-04

Cell therapies for neurological disorders require an extensive knowledge of disease-associated neuropathology and procedures for generating neurons for transplantation. In many patients with severe acquired temporal lobe epilepsy (TLE), the dentate gyrus exhibits sclerosis and GABAergic interneuron degeneration. Mounting evidence suggests that therapeutic benefits can be obtained by transplanting fetal GABAergic progenitors into the dentate gyrus in rodents with TLE, but the scarcity of human fetal cells limits applicability in patient populations. In contrast, virtually limitless quantities of neural progenitors can be obtained from embryonic stem (ES) cells. ES cell-based therapies for neurological repair in TLE require evidence that the transplanted neurons integrate functionally and replace cell types that degenerate. To address these issues, we transplanted mouse ES cell-derived neural progenitors (ESNPs) with ventral forebrain identities into the hilus of the dentate gyrus of mice with TLE and evaluated graft differentiation, mossy fiber sprouting, cellular morphology, and electrophysiological properties of the transplanted neurons. In addition, we compared electrophysiological properties of the transplanted neurons with endogenous hilar interneurons in mice without TLE. The majority of transplanted ESNPs differentiated into GABAergic interneuron subtypes expressing calcium-binding proteins parvalbumin, calbindin, or calretinin. Global suppression of mossy fiber sprouting was not observed; however, ESNP-derived neurons formed dense axonal arborizations in the inner molecular layer and throughout the hilus. Whole-cell hippocampal slice electrophysiological recordings and morphological analyses of the transplanted neurons identified five basic types; most with strong after-hyperpolarizations and smooth or sparsely spiny dendritic morphologies resembling endogenous hippocampal interneurons. Moreover, intracellular recordings of spontaneous EPSCs indicated that

Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

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Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

2016-01-01

Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize

Downregulation of telomerase maintenance-related ACD expression in patients undergoing immunosuppresive therapy following kidney transplantation.

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Witkowska, Agnieszka; Strzalka-Mrozik, Barbara; Owczarek, Aleksander; Gola, Joanna; Mazurek, Urszula; Grzeszczak, Wladyslaw; Gumprecht, Janusz

2015-12-01

Chronic administration of immunosuppressants has been associated with long-term consequences, including a higher risk of neoplasm development. The processes regulating telomere function exert a major influence on human cancer biology. The present study aimed to assess the effect of immunosuppressive therapy on the expression of genes associated with telomere maintenance and protection in patients following renal transplantation. A total of 51 patients that had undergone kidney transplantation and 54 healthy controls were enrolled in the study. The 51 transplant patients received a three-drug immunosuppressive regimen consisting of cyclosporine A, prednisone and mycophenolate mofetil. In stage 1 of the study, the expression profiles of 123 transcripts, which represented 70 genes, were assessed in peripheral mononuclear blood cells using an oligonucleotide microarray technique in 8 transplant recipients and 4 healthy control subjects. Among the analyzed transcripts, the expression levels of 4 differed significantly between the studied groups; however, only the ACD (adrenocortical dysplasia homolog) gene, encoding the telomere-binding protein POT1-interacting protein 1 (TPP1), was sufficiently specific for telomere homeostasis. The expression of ACD was downregulated in transplant recipients (fold change, 2.11; P=0.006). In stage 2 of the study, reverse transcription-quantitative polymerase chain reaction analysis of ACD , DKC1 and hTERT mRNA was conducted for all transplant patients and control subjects. The results confirmed the downregulation of the ACD gene in patients that had received immunosuppressive therapy (P=0.002). The results of the present study indicate that the downregulation of ACD gene transcription, and thus TPP1 protein expression, may enhance the capacity for cell immortalization, despite normal levels of other key telomere maintenance factors, in patients undergoing immunosuppressive therapy. Furthermore, the results indicate that TPP1 has

Endoscopic therapy of posttransplant biliary stenoses after right-sided adult living donor liver transplantation.

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Zoepf, Thomas; Maldonado-Lopez, Evelyn J; Hilgard, Philip; Schlaak, Joerg; Malago, Massimo; Broelsch, Christoph E; Treichel, Ulrich; Gerken, Guido

2005-11-01

Endoscopic treatment of biliary strictures after liver transplantation is a therapeutic challenge. In particular, outcomes of endoscopic therapy of biliary complications in the case of duct-to-duct anastomosis after living related liver transplantation are limited. The aim of this study was to evaluate the feasibility and success of an endoscopic treatment approach to posttransplant biliary strictures (PTBS) after right-sided living donor liver transplantation (RLDLT) with duct-to-duct anastomosis. Ninety patients who received adult-to-adult RLDLT in our center were screened retrospectively with respect to endoscopic treatment of PTBS. Therapy was judged as successful when cholestasis parameters returned to normal and bile duct narrowing was reduced significantly after the completion of therapy. Forty of 90 RLDLT patients received duct-to-duct anastomosis, 12 (30%) showed PTBS. Seven of 12 patients were treated successfully by endoscopy; the remaining 5 patients were treated primarily by surgery. Most patients were treated by balloon dilatation followed by insertion of endoprostheses. A median of 2.5 dilatation sessions were necessary and the median treatment duration was 8 months. One patient developed endoscopy-treatable recurrent stenosis, no surgical intervention was necessary. Mild pancreatitis occurred in 7.9% and cholangitis in 5.3% of the procedures. One minor bleeding episode occurred during sphincterotomy. Bleeding was managed endoscopically. Endoscopic therapy of adult-to-adult right living related liver transplantation with duct-to-duct anastomosis is feasible and frequently is successful. The duct-to-duct anastomosis offers the possibility of endoscopic treatment. Endoscopic treatment of posttransplant biliary strictures is safe, with a low specific complication rate.

[Transplantation in diabetes type 1--current problems and perspectives].

Science.gov (United States)

Wasikowa, Renata; Noczyńska, Anna; Basiak, Aleksander

2004-01-01

Diabetes type 1 is, as we know, a chronic progressive disease, which requires a substitutional therapy with insulin for the whole life. The cause is a definite destruction of the pancreatic beta cells. For many years there have been intensive investigations on the possibility to obtain a complete, persistent withdrawal of the symptoms. Substitution of the destroyed, not active cells, could take place after transplantation of the whole pancreas, transplantation of pancreatic islets or transplantation of stem cells. This is now the only method which may cause an independence from exogenous insulin, persistent normoglycemia, normal HbA1c level, without risk of hypoglycemia. Pancreas and islets transplantations, however, are connected till now with the necessity of an immunosuppressive therapy for the whole life, with the toxicity of the drugs, incidence of frequent infections and malignancy. Pancreas transplantation is a serious surgical intervention, connected with numerous risks and complications, considerably less risk appears in islet cell transplantations. Since 2000 exclusively islet cell transplantations have been performed. One of the leading centers is Edmonton, where professor Shapiro prepared the so called. Edmonton protocol which is characterized by using corticosteroid-free immunosuppressive drugs, islet cells from two or more donors, repeated till the attainment of insulin dependence. A problem now is that the islets are obtained from cadavers. Therefore intensive research is conducted for alternative sources of beta cells. At this moment it is mostly preferred for receiving a sufficient number of insulin producing cells to develop stem cells with a subsequent differentiation to insulin producing cells. The mentioned cells have an unlimited ability of reproduction, in this case also immunosuppressive therapy is not necessary. Alternative sources of beta cells are cells achieved on the genetic engineering, embryonic or adult somatic stem cells. It is

A Patient-Derived Xenograft Model of Parameningeal Embryonal Rhabdomyosarcoma for Preclinical Studies

Directory of Open Access Journals (Sweden)

Jody E. Hooper

2015-01-01

Full Text Available Embryonal rhabdomyosarcoma (eRMS is one of the most common soft tissue sarcomas in children and adolescents. Parameningeal eRMS is a variant that is often more difficult to treat than eRMS occurring at other sites. A 14-year-old female with persistent headaches and rapid weight loss was diagnosed with parameningeal eRMS. She progressed and died despite chemotherapy with vincristine, actinomycin-D, and cyclophosphamide plus 50.4 Gy radiation therapy to the primary tumor site. Tumor specimens were acquired by rapid autopsy and tumor tissue was transplanted into immunodeficient mice to create a patient-derived xenograft (PDX animal model. As autopsy specimens had an ALK R1181C mutation, PDX tumor bearing animals were treated with the pan-kinase inhibitor lestaurtinib but demonstrated no decrease in tumor growth, suggesting that single agent kinase inhibitor therapy may be insufficient in similar cases. This unique parameningeal eRMS PDX model is publicly available for preclinical study.

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review

NARCIS (Netherlands)

Rossen, N.G.; MacDonald, J.K.; Vries, de E.M.; Haens, D' G.R.; Vos, de W.M.; Zoetendal, E.G.; Ponsioen, C.Y.

2015-01-01

AIM: To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review

NARCIS (Netherlands)

Rossen, Noortje G.; Macdonald, John K.; de Vries, Elisabeth M.; D'Haens, Geert R.; de Vos, Willem M.; Zoetendal, Erwin G.; Ponsioen, Cyriel Y.

2015-01-01

To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the

First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

Science.gov (United States)

Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

2014-12-01

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); Paplastic anemia. Copyright© Ferrata Storti Foundation.

Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: A possible role for [{sup 18}F]-FDG-PET(/CT) in initial staging and therapy monitoring

Energy Technology Data Exchange (ETDEWEB)

Falck, C. von [Department of Diagnostic Radiology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany)], E-mail: Falck.Christian.von@mh-hannover.de; Maecker, B. [Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Schirg, E. [Department of Diagnostic Radiology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Boerner, A.R.; Knapp, W.H. [Department of Nuclear Medicine, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Klein, C. [Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany); Galanski, M. [Department of Diagnostic Radiology, Medizinische Hochschule Hannover (Medical School Hanover), Carl-Neuberg-Strasse 1, 30625 Hannover (Germany)

2007-09-15

Post transplant lymphoproliferative disease (PTLD) is a severe complication after solid organ or bone marrow transplantation. In pediatric transplant recipients PTLD is the most common malignancy. The aim of this study was to evaluate a possible role for positron emission tomography with [{sup 18}F]-2-fluoro-2-desoxy-glucose (FDG) in the initial staging and in therapy monitoring of pediatric patients suffering from biopsy-proven CD20-positive PTLD after solid organ transplantation. Seven pediatric patients were included. All available imaging studies - CT (n = 15), MRI (n = 16) and PET/PETCT (n = 16) - were reviewed on a lesion by lesion base. The performance of FDG-PET in the initial staging and during therapy with a chimeric anti-CD20 antibody was compared to conventional cross sectional imaging and correlated with the clinical outcome. FDG-PET identified all sites of disease as shown by CT/MRI and helped to clarify the significance of equivocal findings. The initial stage of disease was correctly identified by FDG-PET alone when compared to CT/MRI. During therapy, FDG-PET was superior to conventional cross-sectional imaging in the early evaluation of response.

Using the cost-effectiveness of allogeneic islet transplantation to inform induced pluripotent stem cell-derived β-cell therapy reimbursement.

Science.gov (United States)

Archibald, Peter R T; Williams, David J

2015-11-01

In the present study a cost-effectiveness analysis of allogeneic islet transplantation was performed and the financial feasibility of a human induced pluripotent stem cell-derived β-cell therapy was explored. Previously published cost and health benefit data for islet transplantation were utilized to perform the cost-effectiveness and sensitivity analyses. It was determined that, over a 9-year time horizon, islet transplantation would become cost saving and 'dominate' the comparator. Over a 20-year time horizon, islet transplantation would incur significant cost savings over the comparator (GB£59,000). Finally, assuming a similar cost of goods to islet transplantation and a lack of requirement for immunosuppression, a human induced pluripotent stem cell-derived β-cell therapy would dominate the comparator over an 8-year time horizon.

Effect of milrinone therapy on splanchnic perfusion after heart transplantation.

Science.gov (United States)

Urbanowicz, Tomasz; Ligowski, Marcin; Camacho, Estillita; Walczak, Maciej; Straburzyńska-Migaj, Ewa; Tomczyk, Jadwiga; Jemielity, Marek

2014-09-23

Milrinone is a selective inhibitor of the cAMP-specific phosphodiesterase III isoenzyme in myocardium and vascular smooth muscle. Milrinone administration following heart transplantation is routine practice. The purpose of this study was to evaluate the influence of milrinone therapy on splanchnic perfusion following heart transplantation. There were 12 patients (10 males and 2 females) with a mean age of 42 ± 12 who underwent heart transplantation. Milrinone parenteral following surgery was started after surgery and continued for the next 67 ± 4 h. Repeated Swann-Ganz measurements and control transthoracic echocardiography were performed. Blood samples were taken to estimate level of lactic acid (LA), liver transaminases, serum amylase, and GFR ratio. The mean time of milrinone administration was 67 ± 4 h. The serum LA increase following milrinone discontinuation was 1.7 ± 0.7 mmol/dm(3) vs. 3.8 ± 0.9 mmol/dm(3), (pmilrinone discontinuation was 79 ± 30 IU/L vs. 135 ± 55 IU/L, pmilrinone withdrawn. There was a progressive increase in serum amylase levels after milrinone was withdrawn (80.6 ± 29 IU/L vs. 134 ± 45 IU/L, pMilrinone withdrawal during the postoperative period was associated with deterioration of splanchnic perfusion, as shown by a transient increase in lactic acid and serum increase of aminotransferases (ALT/ASP) concentration and amylase activity. The study results show the extracardiac effects of milrinone therapy.

TACE: therapy of the HCC before liver transplantation - experiences

International Nuclear Information System (INIS)

Herber, S.; Schneider, J.; Brecher, B.; Thelen, M.; Pitton, M.B.; Hoehler, T.; Otto, G.

2005-01-01

Purpose: Analysis of the course of disease in patients with histologically proven HCC before and after orthotopic liver transplantation (LTx) who received transarterial chemoembolization (TACE). Material and Methods: Thirty-five of a total collective of 363 patients with histologically proven HCC underwent LTx. Before LTx, all patients were treated with sequential TACE. According to treatment pattern, TACE should be performed every 6 weeks, using a suspension consisting of max. 10 mg Mitomycin C as well as 10-30 ml iodized oil (Lipiodol). Patients were classified according to the Milano criteria. Criteria were called exceeded if the tumor size was >5 cm and/or >3 tumors larger than 3 cm were found. Therapy success and liver function were examined by means of spiral CT and laboratory controls. Investigation parameters included the number of tumor knots as well as the maximum tumor size. Additionally, the Lipiodol accumulation, the patency of the portal vein and the occurrence of complications were checked. Results: Altogether, 184 TACE procedures were accomplished (5.3+/-3.3, range 1-14). The waiting period up to the transplantation amounted to 366+/-255 days (range 44-1137). The average number of tumor knots for each patient was 3.1+/-2.2 before and 2.9+/-2.2 after TACE (p=0.887). The average tumor size was 4.2+/-2.5 before and 2.8+/-1.4 after TACE. The Milano criteria to LTx crossed 17/35 patients. Patients with exceeded Milan criteria showed a highly significant size reduction of the tumor after TACE (p=0.001); in 9/17 cases the transplantation criteria were secondarily fulfilled through downstaging. A successful LTx was accomplished in 35/35 cases. Follow up after LTx was 769+/-509 days. The tumor recurrence in patients with exceeded vs. fulfilled transplantation criteria was 11.1% vs. 11.8% (p=0.99). The recurrence free survival was 93.3%, 82.5% and 82.5% at 1, 3 and 5 years, respectively. There were no relevant differences between patients with exceeded vs

Amnion: a potent graft source for cell therapy in stroke.

Science.gov (United States)

Yu, Seong Jin; Soncini, Maddalena; Kaneko, Yuji; Hess, David C; Parolini, Ornella; Borlongan, Cesar V

2009-01-01

Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attracted attention as a novel cell source for cell transplantation therapy. Cells isolated from amniotic membrane can differentiate into all three germ layers, have low immunogenicity and anti-inflammatory function, and do not require the destruction of human embryos for their isolation, thus circumventing the ethical debate commonly associated with the use of human embryonic stem cells. Accumulating evidence now suggests that the amnion, which had been discarded after parturition, is a highly potent transplant material in the field of regenerative medicine. In this report, we review the current progress on the characterization of MSCs derived from the amnion as a remarkable transplantable cell population with therapeutic potential for multiple CNS disorders, especially stroke.

Mouse androgenetic embryonic stem cells differentiated to multiple cell lineages in three embryonic germ layers in vitro.

Science.gov (United States)

Teramura, Takeshi; Onodera, Yuta; Murakami, Hideki; Ito, Syunsuke; Mihara, Toshihiro; Takehara, Toshiyuki; Kato, Hiromi; Mitani, Tasuku; Anzai, Masayuki; Matsumoto, Kazuya; Saeki, Kazuhiro; Fukuda, Kanji; Sagawa, Norimasa; Osoi, Yoshihiko

2009-06-01

The embryos of some rodents and primates can precede early development without the process of fertilization; however, they cease to develop after implantation because of restricted expressions of imprinting genes. Asexually developed embryos are classified into parthenote/gynogenote and androgenote by their genomic origins. Embryonic stem cells (ESCs) derived from asexual origins have also been reported. To date, ESCs derived from parthenogenetic embryos (PgESCs) have been established in some species, including humans, and the possibility to be alternative sources for autologous cell transplantation in regenerative medicine has been proposed. However, some developmental characteristics, which might be important for therapeutic applications, such as multiple differentiation capacity and transplantability of the ESCs of androgenetic origin (AgESCs) are uncertain. Here, we induced differentiation of mouse AgESCs and observed derivation of neural cells, cardiomyocytes and hepatocytes in vitro. Following differentiated embryoid body (EB) transplantation in various mouse strains including the strain of origin, we found that the EBs could engraft in theoretically MHC-matched strains. Our results indicate that AgESCs possess at least two important characteristics, multiple differentiation properties in vitro and transplantability after differentiation, and suggest that they can also serve as a source of histocompatible tissues for transplantation.

Nutritional Therapy in Liver Transplantation

Directory of Open Access Journals (Sweden)

Ahmed Hammad

2017-10-01

Full Text Available Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.

Transplantation of embryonic porcine neocortical tissue into newborn rats

DEFF Research Database (Denmark)

Castro, Anthony J; Meyer, Morten; Møller Dall, Annette

2003-01-01

cavities made in newborn rats. Sacrifice at 3-12.5 weeks posttransplantation revealed healthy looking grafts in several animals. Apparent graft rejection evidenced by areas of necrosis and OX1 reactivity was observed in some of the older transplants. Treatment of nursing mothers or of postweaning newborns...... with cyclosporin A did not appear to promote graft survival. Some transplants grew to extremely large proportions and were characterized by bands of cells and bundles of axons as observed using immunohistochemical staining for pig neurofilament. Neurofilament-positive axons projected from several of the grafts...

Salvage therapy for CLL and the role of stem cell transplantation.

Science.gov (United States)

Gribben, John G

2005-01-01

Chronic lymphocytic leukaemia (CLL) remains an incurable disease and, notwithstanding the excellent remission rates now achieved with purine analogs and monoclonal antibodies, the vast majority of patients with CLL are destined to relapse after primary treatment. The management of relapsed CLL patients is then dependent upon a number of factors, most importantly age, performance status, previous therapy administered, the response and duration of response to such therapy, and time from last therapy. Although prior therapy and response to such therapy are important factors in determining next therapy, it is often difficult to determine their importance from published studies. Furthermore, the goal of therapy, whether palliative or aggressive, must also be weighed into the decision when deciding on the next line of treatment. With many potential treatments available, the sequence of treatments and the timing of procedures such as stem cell transplantation remain controversial and are the focus of ongoing clinical trials.

Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.

Science.gov (United States)

Sugai, Keiko; Fukuzawa, Ryuji; Shofuda, Tomoko; Fukusumi, Hayato; Kawabata, Soya; Nishiyama, Yuichiro; Higuchi, Yuichiro; Kawai, Kenji; Isoda, Miho; Kanematsu, Daisuke; Hashimoto-Tamaoki, Tomoko; Kohyama, Jun; Iwanami, Akio; Suemizu, Hiroshi; Ikeda, Eiji; Matsumoto, Morio; Kanemura, Yonehiro; Nakamura, Masaya; Okano, Hideyuki

2016-09-19

The risk of tumorigenicity is a hurdle for regenerative medicine using induced pluripotent stem cells (iPSCs). Although teratoma formation is readily distinguishable, the malignant transformation of iPSC derivatives has not been clearly defined due to insufficient analysis of histology and phenotype. In the present study, we evaluated the histology of neural stem/progenitor cells (NSPCs) generated from integration-free human peripheral blood mononuclear cell (PBMC)-derived iPSCs (iPSC-NSPCs) following transplantation into central nervous system (CNS) of immunodeficient mice. We found that transplanted iPSC-NSPCs produced differentiation patterns resembling those in embryonic CNS development, and that the microenvironment of the final site of migration affected their maturational stage. Genomic instability of iPSCs correlated with increased proliferation of transplants, although no carcinogenesis was evident. The histological classifications presented here may provide cues for addressing potential safety issues confronting regenerative medicine involving iPSCs.

Rosiglitazone attenuates transplant arteriosclerosis after allogeneic aorta transplantation in rats

NARCIS (Netherlands)

Onuta, Geanina; Rienstra, Heleen; de Boer, Jan Freark; Boer, Mark Walther; Roks, Anton J. M.; Klatter, Flip A.; Uges, Donald R. A.; Navis, Gerjan; Rozing, Jan; Hillebrands, Jan-Luuk

2007-01-01

Background. Transplant arteriosclerosis is a leading cause of chronic transplant dysfunction and is characterized by occlusive neointima formation in intragraft arteries. Development of transplant arteriosclerosis is refractory to conventional immunosuppressive drugs and adequate therapy is not

Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

Directory of Open Access Journals (Sweden)

Agnete Kirkeby

2012-06-01

Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

The primary role of zebrafish nanog is in extra-embryonic tissue.

Science.gov (United States)

Gagnon, James A; Obbad, Kamal; Schier, Alexander F

2018-01-09

The role of the zebrafish transcription factor Nanog has been controversial. It has been suggested that Nanog is primarily required for the proper formation of the extra-embryonic yolk syncytial layer (YSL) and only indirectly regulates gene expression in embryonic cells. In an alternative scenario, Nanog has been proposed to directly regulate transcription in embryonic cells during zygotic genome activation. To clarify the roles of Nanog, we performed a detailed analysis of zebrafish nanog mutants. Whereas zygotic nanog mutants survive to adulthood, maternal-zygotic (MZ nanog ) and maternal mutants exhibit developmental arrest at the blastula stage. In the absence of Nanog, YSL formation and epiboly are abnormal, embryonic tissue detaches from the yolk, and the expression of dozens of YSL and embryonic genes is reduced. Epiboly defects can be rescued by generating chimeric embryos of MZ nanog embryonic tissue with wild-type vegetal tissue that includes the YSL and yolk cell. Notably, cells lacking Nanog readily respond to Nodal signals and when transplanted into wild-type hosts proliferate and contribute to embryonic tissues and adult organs from all germ layers. These results indicate that zebrafish Nanog is necessary for proper YSL development but is not directly required for embryonic cell differentiation. © 2018. Published by The Company of Biologists Ltd.

Survival of partially differentiated mouse embryonic stem cells in the scala media of the guinea pig cochlea.

Science.gov (United States)

Hildebrand, Michael S; Dahl, Hans-Henrik M; Hardman, Jennifer; Coleman, Bryony; Shepherd, Robert K; de Silva, Michelle G

2005-12-01

The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea. Transplanted cells survived in the scala media for a postoperative period of at least nine weeks, evidenced by histochemical and direct fluorescent detection of enhanced green fluorescent protein (EGFP). Transplanted cells were discovered near the spiral ligament and stria vascularis in the endolymph fluid of the scala media. In some cases, cells were observed close to the damaged organ of Corti structure. There was no evidence of significant immunological rejection of the implanted ES cells despite the absence of immunosuppression. Our surgical approach allowed efficient delivery of ES cells to the scala media while preserving the delicate structures of the cochlea. This is the first report of the survival of partially differentiated ES cells in the scala media of the mammalian cochlea, and it provides support for the potential of cell-based therapies for sensorineural hearing impairment.

Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas

Science.gov (United States)

Epperla, Narendranath; Fenske, Timothy S; Hari, Parameswaran N; Hamadani, Mehdi

2015-01-01

Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton’s tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT. PMID:26421260

Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke.

Science.gov (United States)

Peña, Ike dela; Borlongan, Cesar V

2015-12-01

Among recently investigated stroke therapies, stem cell treatment holds great promise by virtue of their putative ability to replace lost cells, promote endogenous neurogenesis,and produce behavioral and functional improvement through their "bystander effects." Translating stem cell in the clinic, however, presents a number of technical difficulties. A strategy suggested to enhance therapeutic utility of stem cells is combination therapy, i.e., co-transplantation of stem cells or adjunct treatment with pharmacological agents and substrates,which is assumed to produce more profound therapeutic benefits by circumventing limitations of individual treatments and facilitating complementary brain repair processes. We previously demonstrated enhanced functional effects of cotreatment with granulocyte-colony stimulating factor (GCSF)and human umbilical cord blood cell (hUCB) transplantation in animal models of traumatic brain injury (TBI). Here,we suggest that the aforementioned combination therapy may also produce synergistic effects in stroke. Accordingly, G-CSF treatment may reduce expression of pro-inflammatory cytokines and enhance neurogenesis rendering a receptive microenvironment for hUCB engraftment. Adjunct treatment of GCSF with hUCB may facilitate stemness maintenance and guide neural lineage commitment of hUCB cells. Moreover, regenerative mechanisms afforded by G-CSF-mobilized endogenous stem cells, secretion of growth factors by hUCB grafts and G-CSF-recruited endothelial progenitor cells(EPCs), as well as the potential graft–host integration that may promote synaptic circuitry re-establishment could altogether produce more pronounced functional improvement in stroked rats subjected to a combination G-CSF treatment and hUCB transplantation. Nevertheless, differences in pathology and repair processes underlying TBI and stroke deserve consideration when testing the effects of combinatorial G-CSF and hUCB cell transplantation for stroke treatment. Further

Targeting embryonic signaling pathways in cancer therapy.

Science.gov (United States)

Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

2012-01-01

The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

Electrical stimulation of transplanted motoneurons improves motor unit formation

Science.gov (United States)

Liu, Yang; Grumbles, Robert M.

2014-01-01

Motoneurons die following spinal cord trauma and with neurological disease. Intact axons reinnervate nearby muscle fibers to compensate for the death of motoneurons, but when an entire motoneuron pool dies, there is complete denervation. To reduce denervation atrophy, we have reinnervated muscles in Fisher rats from local transplants of embryonic motoneurons in peripheral nerve. Since growth of axons from embryonic neurons is activity dependent, our aim was to test whether brief electrical stimulation of the neurons immediately after transplantation altered motor unit numbers and muscle properties 10 wk later. All surgical procedures and recordings were done in anesthetized animals. The muscle consequences of motoneuron death were mimicked by unilateral sciatic nerve section. One week later, 200,000 embryonic day 14 and 15 ventral spinal cord cells, purified for motoneurons, were injected into the tibial nerve 10–15 mm from the gastrocnemii muscles as the only neuron source for muscle reinnervation. The cells were stimulated immediately after transplantation for up to 1 h using protocols designed to examine differential effects due to pulse number, stimulation frequency, pattern, and duration. Electrical stimulation that included short rests and lasted for 1 h resulted in higher motor unit counts. Muscles with higher motor unit counts had more reinnervated fibers and were stronger. Denervated muscles had to be stimulated directly to evoke contractions. These results show that brief electrical stimulation of embryonic neurons, in vivo, has long-term effects on motor unit formation and muscle force. This muscle reinnervation provides the opportunity to use patterned electrical stimulation to produce functional movements. PMID:24848463

One year results of preoperative single bolus ATG-Fresenius induction therapy in sensitized renal transplant recipients.

Science.gov (United States)

Wang, D; Chen, J H; Wu, W Z; Yang, S L; Wu, G J; Wang, H; Tan, J M

2007-01-01

Sensitization in kidney transplantation is associated with more acute rejections, inferior graft survival, and an increase in delayed graft function. This study was designed to evaluate the efficacy and safety of preoperative single bolus antithymocyte globulin (ATG) induction therapy in sensitized renal transplant recipients. Fifty-six cadaveric donor kidney transplant recipients were divided into two groups: Group I (nonsensitized group, n = 30) and group II (sensitized group, PRA>10%, n = 26). ATG was given as a single preoperative bolus induction therapy to group II (ATG IV; 9 mg/kg). The group I patients were treated with mycophenolate mofetil preoperatively as induction therapy. The basic immunosuppressive regimen included tacrolimus (FK-506) or cyclosporine, mycophenolate mofetil, and prednisolone. After hospital discharge, patients were followed on a routine outpatient basis for 12 months. Acute rejection episodes (ARE) occurred in 20% (6/30) of group I and 15.38% (4/26) of group II patients (P = NS). Infections occurred in eight patients (26.7%) as 11 episodes (36.7%), averaging 1.4 episodes per infected patient in group 1, and 6 patients (23.1%) for a total of 10 episodes (38.5%), averaging 1.7 episodes per infected patient, in group II (P = NS). Occurrence of side effects and hospital stay were almost comparable in the two groups. No delayed graft function was observed in either group. The 12-month actuarial patient and graft survival were 100% in Group I and II. A preoperative single bolus ATG induction therapy was an effective and safe therapeutic measure, yielding an acceptable acute rejection rate in presensitized renal transplant recipients.

Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

Science.gov (United States)

Peterson, Christopher W; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Jerome, Keith R; Hu, Shiu-Lok; Holmes, Michael C; Estes, Jacob D; Kiem, Hans-Peter

2018-04-01

Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

Directory of Open Access Journals (Sweden)

Christopher W Peterson

2018-04-01

Full Text Available Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP model of latent infection using simian/human immunodeficiency virus (SHIV and combination antiretroviral therapy (cART in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05, relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

NARCIS (Netherlands)

Graaf, Ymke Grete Leontien de

2008-01-01

Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy.

Plasticity and regeneration in the injured spinal cord after cell transplantation therapy.

Science.gov (United States)

Nori, Satoshi; Nakamura, Masaya; Okano, Hideyuki

2017-01-01

Spinal cord injury (SCI) typically damages the long axonal tracts of the spinal cord which results in permanent disability. However, regeneration of the injured spinal cord is approaching reality according to the advances in stem cell biology. Cell transplantation therapy holds potential to lead to recovery following SCI through some positive mechanisms. Grafted cells induce plasticity and regeneration in the injured spinal cord by promoting remyelination of damaged axons, reconstruction of neural circuits by synapse formation between host neurons and graft-derived neurons, and secreting neurotrophic factors to promote axonal elongation as well as reduce retrograde axonal degeneration. In this review, we will delineate (1) the microenvironment of the injured spinal cord that influence the plasticity and regeneration capacity after SCI, (2) a number of different kinds of cell transplantation therapies for SCI that has been extensively studied by researchers, and (3) potential mechanisms of grafted cell-induced regeneration and plasticity in the injured spinal cord. © 2017 Elsevier B.V. All rights reserved.

A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver

International Nuclear Information System (INIS)

Shikanai, Mima; Asahina, Kinji; Iseki, Sachiko; Teramoto, Kenichi; Nishida, Tomohiro; Shimizu-Saito, Keiko; Ota, Masato; Eto, Kazuhiro; Teraoka, Hirobumi

2009-01-01

Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepatic developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or α-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells became mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse embryonic stem cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.

Human embryonic stem cell derived islet progenitors mature inside an encapsulation device without evidence of increased biomass or cell escape.

Science.gov (United States)

Kirk, Kaitlyn; Hao, Ergeng; Lahmy, Reyhaneh; Itkin-Ansari, Pamela

2014-05-01

There are several challenges to successful implementation of a cell therapy for insulin dependent diabetes derived from human embryonic stem cells (hESC). Among these are development of functional insulin producing cells, a clinical delivery method that eliminates the need for chronic immunosuppression, and assurance that hESC derived tumors do not form in the patient. We and others have shown that encapsulation of cells in a bilaminar device (TheraCyte) provides immunoprotection in rodents and primates. Here we monitored human insulin secretion and employed bioluminescent imaging (BLI) to evaluate the maturation, growth, and containment of encapsulated islet progenitors derived from CyT49 hESC, transplanted into mice. Human insulin was detectable by 7 weeks post-transplant and increased 17-fold over the course of 8 weeks, yet during this period the biomass of encapsulated cells remained constant. Remarkably, by 20 weeks post-transplant encapsulated cells secreted sufficient levels of human insulin to ameliorate alloxan induced diabetes. Further, bioluminescent imaging revealed for the first time that hESCs remained fully contained in encapsulation devices for up to 150 days, the longest period tested. Collectively, the data suggest that encapsulated hESC derived islet progenitors hold great promise as an effective and safe cell replacement therapy for insulin dependent diabetes. Copyright © 2014. Published by Elsevier B.V.

Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

LENUS (Irish Health Repository)

Gabardi, Steven

2011-09-01

To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation.

Adherence to immunosuppressive therapy following liver transplantation: an integrative review.

Science.gov (United States)

Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito

2016-08-29

to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill. investigar as evidências disponíveis na literatura sobre a não adesão à terapêutica imunossupressora entre pacientes submetidos ao transplante de fígado. revisão integrativa da literatura, que incluiu investigações cuja amostra era composta por pacientes com idade igual ou superior a 18 anos, submetidos a transplante de fígado. Excluíram-se as que continham pacientes submetidos a transplantes de múltiplos órgãos. Para a seleção dos artigos foram consultadas as bases Medline/Pubmed, CINAHL, LILACS, Scopus e Embase. O período de busca determinado correspondeu à data inicial de indexação das

Retinal stem cells and potential cell transplantation treatments

Directory of Open Access Journals (Sweden)

Tai-Chi Lin

2014-11-01

Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

Parthenogenetic embryonic stem cells with H19 siRNA-mediated knockdown as a potential resource for cell therapy.

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Kwak, Minhye; Hong, Su; Yu, Seong-Lan; Sim, Bo-Woong; Seo, Jeong-Sun; Kang, Jaeku

2012-02-01

Embryonic stem (ES) cells are used in cell therapy and tissue engineering due to their ability to produce different cells types. However, studies of ES cells that are derived from fertilized embryos have raised concerns about the limitations imposed by ethical and political considerations. Therefore, many studies of stem cells use the stem cells that are derived from unfertilized oocytes and adult tissue. Although parthenogenetic embryonic stem (ESP) cells also avoid ethical and political dilemmas and can be used in cell-based therapy, the ESP cells exhibit growth retardation problems. Therefore, to investigate the potential for muscle growth from genetically modified ESP cells, we established four ES cell types, including normal embryonic stem (ESN) cells, ESP cells, ESP cells that overexpress the insulin-like growth factor 2 (Igf2) gene (ESI) and ESP cells with down-regulated H19 gene expression (ESH). Using these cells, we examined the expression profiles of genes that were related to imprinting and muscle using microarrays. The gene expression patterns of ESI and ESH cells were similar and were more closely related to the ESN pattern than that of the ESP cells. Differentiated ESH cells exhibited increased expression of bone morphologic protein 4 (BMP4), which is a mesoderm marker, compared with the differentiated ESI cells. We showed that Igf2 expression was induced by H19 silencing in the ESP cells via hypermethylation of the H19 imprinting control region 1 (ICR1). Moreover, the proportion of ESH-derived chimera was slightly higher than those produced from the ESP cells. In addition, we detected increased cell proliferation in the MEF cells following H19 knock-down. These results indicate that the ESH cells may be a source of cell-based therapy for conditions such as muscular atrophy.

Nicotinamide induces differentiation of embryonic stem cells into insulin-secreting cells

International Nuclear Information System (INIS)

Vaca, Pilar; Berna, Genoveva; Araujo, Raquel; Carneiro, Everardo M.; Bedoya, Francisco J.; Soria, Bernat; Martin, Franz

2008-01-01

The poly(ADP-ribose) polymerase (PARP) inhibitor, nicotinamide, induces differentiation and maturation of fetal pancreatic cells. In addition, we have previously reported evidence that nicotinamide increases the insulin content of cells differentiated from embryonic stem (ES) cells, but the possibility of nicotinamide acting as a differentiating agent on its own has never been completely explored. Islet cell differentiation was studied by: (i) X-gal staining after neomycin selection; (ii) BrdU studies; (iii) single and double immunohistochemistry for insulin, C-peptide and Glut-2; (iv) insulin and C-peptide content and secretion assays; and (v) transplantation of differentiated cells, under the kidney capsule, into streptozotocin (STZ)-diabetic mice. Here we show that undifferentiated mouse ES cells treated with nicotinamide: (i) showed an 80% decrease in cell proliferation; (ii) co-expressed insulin, C-peptide and Glut-2; (iii) had values of insulin and C-peptide corresponding to 10% of normal mouse islets; (iv) released insulin and C-peptide in response to stimulatory glucose concentrations; and (v) after transplantation into diabetic mice, normalized blood glucose levels over 7 weeks. Our data indicate that nicotinamide decreases ES cell proliferation and induces differentiation into insulin-secreting cells. Both aspects are very important when thinking about cell therapy for the treatment of diabetes based on ES cells

Novel therapies and their integration into allogeneic stem cell transplant for chronic lymphocytic leukemia.

Science.gov (United States)

Jaglowski, Samantha M; Byrd, John C

2012-01-01

Over the past decade, numerous advances have been made in elucidating the biology of and improving treatment for chronic lymphocytic leukemia (CLL). These studies have led to identification of select CLL patient groups that generally have short survival dating from time of treatment or initial disease relapse who benefit from more aggressive therapeutic interventions. Allogeneic transplantation represents the only potentially curative option for CLL, but fully ablative regimens applied in the past have been associated with significant morbidity and mortality. Reduced-intensity preparative regimens has made application of allogeneic transplant to CLL patients much more feasible and increased the number of patients proceeding to this modality. Arising from this has been establishment of guidelines where allogeneic stem cell transplantation should be considered in CLL. Introduction of new targeted therapies with less morbidity, which can produce durable remissions has the potential to redefine where transplantation is initiated in CLL. This review briefly summarizes the field of allogeneic stem cell transplant in CLL and the interface of new therapeutics with this modality. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Antibody induction therapy for lung transplant recipients

DEFF Research Database (Denmark)

Penninga, Luit; Møller, Christian H; Penninga, Ida Elisabeth Irene

2013-01-01

Lung transplantation has become a valuable and well-accepted treatment option for most end-stage lung diseases. Lung transplant recipients are at risk of transplanted organ rejection, and life-long immunosuppression is necessary. Clear evidence is essential to identify an optimal, safe and effect...... and effective immunosuppressive treatment strategy for lung transplant recipients. Consensus has not yet been achieved concerning use of immunosuppressive antibodies against T-cells for induction following lung transplantation....

Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3

International Nuclear Information System (INIS)

Noyes, William R.; Rodriguez, Rey; Knechtle, Stuart J.; Pirsch, John D.; Sollinger, Hans W.; D'Alessandro, Anthony M.; Chappell, Rick; Belzer, Folkert O.; Kinsella, Timothy J.

1996-01-01

Purpose: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. Methods and Materials: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. Results: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months). Conclusion: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant

Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease.

Science.gov (United States)

Rowland, Nathan C; Starr, Philip A; Larson, Paul S; Ostrem, Jill L; Marks, William J; Lim, Daniel A

2015-02-01

Cell transplantation and gene therapy each show promise to enhance the treatment of Parkinson's disease (PD). However, because cell transplantation and gene therapy generally require direct delivery to the central nervous system, clinical trial design involves unique scientific, ethical, and financial concerns related to the invasive nature of the procedure. Typically, such biologics have been tested in PD patients who have not received any neurosurgical intervention. Here, we suggest that PD patients undergoing deep brain stimulation (DBS) device implantation are an ideal patient population for the clinical evaluation of cell transplantation and gene therapy. Randomizing subjects to an experimental group that receives the biologic concurrently with the DBS implantation-or to a control group that receives the DBS treatment alone-has several compelling advantages. First, this study design enables the participation of patients likely to benefit from DBS, many of whom simultaneously meet the inclusion criteria of biologic studies. Second, the need for a sham neurosurgical procedure is eliminated, which may reduce ethical concerns, promote patient recruitment, and enhance the blinding of surgical trials. Third, testing the biologic by "piggybacking" onto an established, reimbursable procedure should reduce the cost of clinical trials, which may allow a greater number of biologics to reach this critical stage of research translation. Finally, this clinical trial design may lead to combinatorial treatment strategies that provide PD patients with more durable control over disabling motor symptoms. By combining neuromodulation with biologics, we may also reveal important treatment paradigms relevant to other diseases of the brain. © 2014 International Parkinson and Movement Disorder Society.

In Utero Hepatocellular Transplantation in Rats

Directory of Open Access Journals (Sweden)

Emma Muñoz-Sáez

2013-01-01

Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

Osteosarcoma target therapy with stem cell transplant: A case review

International Nuclear Information System (INIS)

Fawzy, A.

2005-01-01

Full text: Radioisotopes with medium-energy beta emission and half life of a few days are attractive option for systemic delivery of targeted irradiation. Samarium-153 ethylene diamine tetra-ethylene phosphonale (153Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic osseous lesion. The usual dose of Sm-153 in metastatic disease is 1mCi/Kg (37MBq/Kg) and the dose limiting toxicity is thrombocytopenia. As local radiotherapy has only a limited therapeutic role in the treatment of osteosarcoma, and some types of the tumour portray an unpredictable response to chemotherapy. High dose Sm-153 (30mCi/Kg) was proposed for the target management of recurrent osteosarcoma, this was followed by stem cell transplant (peripheral-blood progenitor, PBPCs). A female child, 10 years old, with polyostotic osteosarcoma with local recurrence in the right hipbone was chosen for therapy. She had left knee prosthesis, right lower limb dis-articulation, and was given chemotherapy in multiple regions. She was subjected to MDP bone scan showing active uptake in an expanding bone lesion in the right hip bone, and was also subjected to MIBI scan, which showed negative uptake. She received 30mCi/Kg Sm-153 (660mCi in total dose), with no major events occurring in the post-injection period. After 10 days the patient went into pancytopenia, which necessitated haematological support. By day 14, there was minimal radiation in the whole body image and the child received her bone marrow transplant. There was marked improvement in the tumour size after 6 weeks of therapy, with improvement in the alkaline phosphatase level (from 1350Iu, before treatment to 350 post treatment). This was confirmed by serial MDP bone scan. High dose Sm-153 with stem cell transplant is considered view a promising method in the management of osteosarcoma. (author)

Primary tacrolimus (FK506) therapy and the long-term risk of post-transplant lymphoproliferative disease in pediatric liver transplant recipients.

Science.gov (United States)

Cacciarelli, T V; Reyes, J; Jaffe, R; Mazariegos, G V; Jain, A; Fung, J J; Green, M

2001-10-01

While the overall incidence of post-transplant lymphoproliferative disease (PTLD) in pediatric liver transplant recipients has been reported to be 4-11%, the long-term risk of PTLD associated with primary tacrolimus therapy is unknown. Therefore, in order to determine the incidence and long-term risk of PTLD, the present study examined 131 pediatric recipients who underwent liver transplantation (LTx) between October 1989 and December 1991 and received primary tacrolimus therapy. This cohort of children was evaluated over an extended time-period (until December 31 1996) with a mean follow-up of 6.3 yr. Actuarial Kaplan-Meier analysis was utilized to determine the risk of PTLD over time. The overall incidence of PTLD was 13% (17/131) with an average age of 4.3 +/- 0.75 yr at diagnosis. Pretransplant Epstein-Barr virus (EBV) serologies were negative in 82%, positive in 12%, and not available in 6% of the patients. The median time to diagnosis of PTLD post-Tx was 11.9 months (mean 16.4 +/- 3.9, range 1.7-63.0 months). Mean tacrolimus dose and plasma trough level (as evaluated by enzyme-linked immunosorbent assay [ELISA]) at the time of diagnosis was 0.32 +/- 0.06 mg/kg/day and 1.3 +/- 0.3 ng/mL, respectively. The cumulative long-term risk of PTLD was found to increase over time: 3% at 6 months, 8% at 1 yr, 12% at 2 yr, 14% at 3 yr, and 15% at 4 and 5 yr. Mortality from PTLD was 12% (two of 17 patients). Primary tacrolimus use in pediatric LTx has a long-term risk of PTLD approaching 15%, with the majority of episodes (78%) occurring in the first 2 yr, suggesting that intense EBV surveillance should occur early post-transplantation.

Intrinsic control of electroresponsive properties of transplanted mammalian brain neurons

DEFF Research Database (Denmark)

Hounsgaard, J; Yarom, Y

1985-01-01

The present study presents the first analysis of neurons in mammalian brain transplants based on intracellular recording. The results, obtained in brain slices including both donor and host tissue, showed that neuronal precursor cells in embryonic transplants retained their ability to complete...... their normal differentiation of cell-type-specific electroresponsive properties. Distortions in cell aggregation and synaptic connectivity did not affect this aspect of neuronal differentiation....

Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

International Nuclear Information System (INIS)

Tsuno, Hiroaki; Yoshida, Toshiko; Nogami, Makiko; Koike, Chika; Okabe, Motonori; Noto, Zenko; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

2012-01-01

Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived Hematopoietic Progenitor Engraftment In Vivo.

Science.gov (United States)

Thompson, Heather L; van Rooijen, Nico; McLelland, Bryce T; Manilay, Jennifer O

2016-01-01

Understanding how embryonic stem cells and their derivatives interact with the adult host immune system is critical to developing their therapeutic potential. Murine embryonic stem cell-derived hematopoietic progenitors (ESHPs) were generated via coculture with the bone marrow stromal cell line, OP9, and then transplanted into NOD.SCID.Common Gamma Chain (NSG) knockout mice, which lack B, T, and natural killer cells. Compared to control mice transplanted with adult lineage-negative bone marrow (Lin - BM) progenitors, ESHP-transplanted mice attained a low but significant level of donor hematopoietic chimerism. Based on our previous studies, we hypothesized that macrophages might contribute to the low engraftment of ESHPs in vivo . Enlarged spleens were observed in ESHP-transplanted mice and found to contain higher numbers of host F4/80 + macrophages compared to BM-transplanted controls. In vivo depletion of host macrophages using clodronate-loaded liposomes improved the ESHP-derived hematopoietic chimerism in the spleen but not in the BM. F4/80 + macrophages demonstrated a striking propensity to phagocytose ESHP targets in vitro . Taken together, these results suggest that macrophages are a barrier to both syngeneic and allogeneic ESHP engraftment in vivo .

Successful Fecal Microbiota Transplantation in a Patient with Severe Complicated Clostridium difficile Infection after Liver Transplantation

Directory of Open Access Journals (Sweden)

Kai Markus Schneider

2018-02-01

Full Text Available Clostridium difficile infection (CDI represents one of the most common healthcare-associated infections. Due to increasing numbers of recurrences and therapy failures, CDI has become a major disease burden. Studies have shown that fecal microbiota transplantation (FMT can both be a safe and highly efficacious therapy for patients with therapy-refractory CDI. However, patients undergoing solid organ transplantation are at high risk for CDI due to long-term immunosuppression, previous antibiotic therapy, and proton pump inhibitor use. Additionally, these patients may be especially prone to adverse events related to FMT. Here, we report a successful FMT in a patient with severe therapy-refractory CDI after liver transplantation.

Culture conditions have an impact on the maturation of traceable, transplantable mouse embryonic stem cell-derived otic progenitor cells.

Science.gov (United States)

Abboud, Nesrine; Fontbonne, Arnaud; Watabe, Isabelle; Tonetto, Alain; Brezun, Jean Michel; Feron, François; Zine, Azel

2017-09-01

The generation of replacement inner ear hair cells (HCs) remains a challenge and stem cell therapy holds the potential for developing therapeutic solutions to hearing and balance disorders. Recent developments have made significant strides in producing mouse otic progenitors using cell culture techniques to initiate HC differentiation. However, no consensus has been reached as to efficiency and therefore current methods remain unsatisfactory. In order to address these issues, we compare the generation of otic and HC progenitors from embryonic stem (ES) cells in two cell culture systems: suspension vs. adherent conditions. In the present study, an ES cell line derived from an Atoh1-green fluorescent protein (GFP) transgenic mouse was used to track the generation of otic progenitors, initial HCs and to compare these two differentiation systems. We used a two-step short-term differentiation method involving an induction period of 5 days during which ES cells were cultured in the presence of Wnt/transforming growth factor TGF-β inhibitors and insulin-like growth factor IGF-1 to suppress mesoderm and reinforce presumptive ectoderm and otic lineages. The generated embryoid bodies were then differentiated in medium containing basic fibroblast growth factor (bFGF) for an additional 5 days using either suspension or adherent culture methods. Upon completion of differentiation, quantitative polymerase chain reaction analysis and immunostaining monitored the expression of otic/HC progenitor lineage markers. The results indicate that cells differentiated in suspension cultures produced cells expressing otic progenitor/HC markers at a higher efficiency compared with the production of these cell types within adherent cultures. Furthermore, we demonstrated that a fraction of these cells can incorporate into ototoxin-injured mouse postnatal cochlea explants and express MYO7A after transplantation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons

Vacuum-assisted closure (VAC) therapy in the management of wound infection following renal transplantation.

Science.gov (United States)

Shrestha, B M; Nathan, V C; Delbridge, M C; Parker, K; Throssell, D; McKane, W S; Karim, M S; Raftery, A T

2007-01-01

Wound infection in the setting of immunosuppressed state such as renal transplantation (RT) causes significant morbidity from sepsis, prolongs hospital stay and is expensive. Vacuum-assisted closure (VAC) therapy is a new technique of management of wound based on the principle of application of controlled negative pressure. The aim of this study was to assess the efficacy of VAC therapy in the management of wound infection following RT. This is a prospective study of a cohort of 180 consecutive RTs performed over a period of 4 years, where the data were retrieved from a prospectively maintained computerised database and case-notes. 9 of 180 (5%) patients developed wound infection following RT which led to cavitations and dehiscence with copious discharge, and refused to heal with conventional treatment. All 9 cases were treated with VAC therapy. The VAC system was removed after a median of 9 (range 3-30) days when discharge from the wound ceased. Four patients were discharged home with portable VAC device and managed on an outpatient basis, where the system was removed after a median 5.5 (range 3-7) days. The median hospital stay after initiation of VAC therapy was significantly shorter (5, range 2-12 days) than on conventional treatment prior to VAC therapy (11, range, 5-20 days) (p=0.003). Complete healing was achieved in all cases. The use of VAC therapy is an effective and safe adjunct to conventional and established treatment modalities for the management of wound infection and dehiscence following RT. Key words: Renal transplantation, wound infection, vacuum-assisted closure therapy.

Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

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Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

2018-03-01

Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

N-acetylcysteine-pretreated human embryonic mesenchymal stem cell administration protects against bleomycin-induced lung injury.

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Wang, Qiao; Zhu, Hong; Zhou, Wu-Gang; Guo, Xiao-Can; Wu, Min-Juan; Xu, Zhen-Yu; Jiang, Jun-feng; Shen, Ce; Liu, Hou-Qi

2013-08-01

The transplantation of mesenchymal stem cells (MSCs) has been reported to be a promising approach in the treatment of acute lung injury. However, the poor efficacy of transplanted MSCs is one of the serious handicaps in the progress of MSC-based therapy. Therefore, the purpose of this study was to investigate whether the pretreatment of human embryonic MSCs (hMSCs) with an antioxidant, namely N-acetylcysteine (NAC), can improve the efficacy of hMSC transplantation in lung injury. In vitro, the antioxidant capacity of NAC-pretreated hMSCs was assessed using intracellular reactive oxygen species (ROS) and glutathione assays and cell adhesion and spreading assays. In vivo, the therapeutic potential of NAC-pretreated hMSCs was assessed in a bleomycin-induced model of lung injury in nude mice. The pretreatment of hMSCs with NAC improved antioxidant capacity to defend against redox imbalances through the elimination of cellular ROS, increasing cellular glutathione levels, and the enhancement of cell adhesion and spreading when exposed to oxidative stresses in vitro. In addition, the administration of NAC-pretreated hMSCs to nude mice with bleomycin-induced lung injury decreased the pathological grade of lung inflammation and fibrosis, hydroxyproline content and numbers of neutrophils and inflammatory cytokines in bronchoalveolar lavage fluid and apoptotic cells, while enhancing the retention and proliferation of hMSCs in injured lung tissue and improving the survival rate of mice compared with results from untreated hMSCs. The pretreatment of hMSCs with NAC could be a promising therapeutic approach to improving cell transplantation and, therefore, the treatment of lung injury.

Music Therapy for Patients Who Have Undergone Hematopoietic Stem Cell Transplant

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Chelsea G. Ratcliff

2014-01-01

Full Text Available Objectives. This study examines the short- and long-term QOL benefits of a music therapy intervention for patients recovering from hematopoietic stem cell transplantation (HSCT. Methods. Ninety allogeneic HSCT patients, after transplant, were randomized to receive ISO-principle (i.e., mood matching based music therapy (MT; n=29, unstructured music (UM; n=30, or usual care (UC; n=31 for four weeks. The ISO principle posits that patients may shift their mood from one state to another by listening to music that is “equal to” the individual’s initial mood state and subsequently listening to music selections that gradually shift in tempo and mood to match the patient’s desired disposition. Participants in MT and UM groups developed two audio CDs to help them feel more relaxed and energized and were instructed to use the CDs to improve their mood as needed. Short-term effects on mood and long-term effects on QOL were examined. Results. MT and UM participants reported improved mood immediately after listening to CDs; the within-group effect was greater for UM participants compared to MT participants. Participant group was not associated with long-term QOL outcomes. Conclusions. Music listening improves mood acutely but was not associated with long-term benefits in this study.

Music therapy for patients who have undergone hematopoietic stem cell transplant.

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Ratcliff, Chelsea G; Prinsloo, Sarah; Richardson, Michael; Baynham-Fletcher, Laura; Lee, Richard; Chaoul, Alejandro; Cohen, Marlene Z; de Lima, Marcos; Cohen, Lorenzo

2014-01-01

Objectives. This study examines the short- and long-term QOL benefits of a music therapy intervention for patients recovering from hematopoietic stem cell transplantation (HSCT). Methods. Ninety allogeneic HSCT patients, after transplant, were randomized to receive ISO-principle (i.e., mood matching) based music therapy (MT; n = 29), unstructured music (UM; n = 30), or usual care (UC; n = 31) for four weeks. The ISO principle posits that patients may shift their mood from one state to another by listening to music that is "equal to" the individual's initial mood state and subsequently listening to music selections that gradually shift in tempo and mood to match the patient's desired disposition. Participants in MT and UM groups developed two audio CDs to help them feel more relaxed and energized and were instructed to use the CDs to improve their mood as needed. Short-term effects on mood and long-term effects on QOL were examined. Results. MT and UM participants reported improved mood immediately after listening to CDs; the within-group effect was greater for UM participants compared to MT participants. Participant group was not associated with long-term QOL outcomes. Conclusions. Music listening improves mood acutely but was not associated with long-term benefits in this study.

Structure-function Evaluation of Stem Cell Therapies for Spinal Cord Injury.

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Zhang, Fuguo

2018-02-23

Spinal cord injuries (SCI) are prevalent, devastating for quality and expectancy of life, and cause heavy economic burdens. Stem cell therapies hold promise in complete structural and functional restoration of SCI. This review focuses on the methods currently used to evaluate the stem cell therapies for SCI. Various kinds of stem cells involving embryonic stem cells (ESCs), bone marrow stromal cells (BMSCs), neural stem cells (NSCs) and induced pluripotent stem cells (iPSCs) are extensively used in regenerative research of SCI. For evaluation, the survival and integration of transplanted cells, spinal cord reconstruction and functional recovery all should be considered. Histological and histochemistrical, microscopic, and colorimetric assays, and real-time RT-PCR techniques are applied to determine the outcome. From the three main aspects-transplanted cells, spinal cord structure, and functional recovery-we summarize and discuss these methods with certain instances of applications in SCI models. Importantly, for the evaluations of function, neuronal transmitting, electrophysiological analysis and behavioral score are included. Wider conjunction of established technologies, as well as the further development of nondestructive methods might make a big difference in testing stem cell therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

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Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

2012-12-01

Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

Prevention and treatment of relapse after stem cell transplantation by cellular therapies.

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Falkenburg, Fred; Ruggiero, Eliana; Bonini, Chaira; Porter, David; Miller, Jeff; Malard, Floran; Mohty, Mohamad; Kröger, Nicolaus; Kolb, Hans Jochem

2018-05-24

Despite recent advances in reducing therapy-related mortality after allogeneic stem cell transplantation (alloSCT) relapse remains the major cause of treatment failure and little progress has been achieved in the last decades. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg/Germany in November 2016 international experts presented and discussed recent developments in the field. Here, the potential of cellular therapies including unspecific and specific T cells, genetically modified T cells, CAR-T cells, NK-cells, and second allografting in prevention and treatment of relapse after alloSCT are summarized.

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

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Hudson, Lauren E.; Anderson, Sarah E.; Corbett, Anita H.

2016-01-01

SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases. PMID:27856521

[Gene therapy and cell transplantation for Parkinson's disease].

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Muramatsu, Shin-ichi

2005-11-01

Increasing enthusiasm in the field of stem cell research is raising the hope of novel cell replacement therapies for Parkinson's disease (PD), but it also raises both scientific and ethical concerns. In most cases, dopaminergic cells are transplanted ectopically into the striatum instead of the substantia nigra. If the main mechanism underlying any observed functional recovery with these cell replacement therapies is restoration of dopaminergic neurotransmission, then viral vector-mediated gene delivery of dopamine-synthesizing enzymes is a more straight forward approach. The development of a recombinant adeno-associated viral (AAV) vector is making gene therapy for PD a feasible therapeutic option in the clinical arena. Efficient and long-term expression of genes for dopamine-synthesizing enzymes in the striatum restored local dopamine production and allowed behavioral recovery in animal models of PD. A clinical trial to evaluate the safety and efficacy of AAV vector-mediated gene transfer of aromatic L-amino acid decarboxylase, an enzyme that converts L-dopa to dopamine, is underway. With this strategy patients would still need to take L-dopa to control their PD symptoms, however, dopamine production could be regulated by altering the dose of L-dopa. Another AAV vector-based clinical trial is also ongoing in which the subthalamic nucleus is transduced to produce inhibitory transmitters.

Embryoid bodies formation and differentiation from mouse embryonic stem cells in collagen/Matrigel scaffolds.

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Zhou, Jin; Zhang, Ye; Lin, Qiuxia; Liu, Zhiqiang; Wang, Haibin; Duan, Cuimi; Wang, Yanmeng; Hao, Tong; Wu, Kuiwu; Wang, Changyong

2010-07-01

Embryonic stem (ES) cells have the potential to develop into any type of tissue and are considered as a promising source of seeding cells for tissue engineering and transplantation therapy. The main catalyst for ES cells differentiation is the growth into embryoid bodies (EBs), which are utilized widely as the trigger of in vitro differentiation. In this study, a novel method for generating EBs from mouse ES cells through culture in collagen/Matrigel scaffolds was successfully established. When single ES cells were seeded in three dimensional collagen/Matrigel scaffolds, they grew into aggregates gradually and formed simple EBs with circular structures. After 7 days' culture, they formed into cystic EBs that would eventually differentiate into the three embryonic germ layers. Evaluation of the EBs in terms of morphology and potential to differentiate indicated that they were typical in structure and could generate various cell types; they were also able to form into tissue-like structures. Moreover, with introduction of ascorbic acid, ES cells differentiated into cardiomyocytes efficiently and started contracting synchronously at day 19. The results demonstrated that collagen/Matrigel scaffolds supported EBs formation and their subsequent differentiation in a single three dimensional environment. Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Generation of hematopoietic lineage cells from embryonic like cells

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Gholam Reza Khamisipour

2014-10-01

Full Text Available Background: Epigenetic reprogramming of somatic cells into embryonic stem cells has attracted much attention, because of the potential for stem cell transplantation and compatibility with recipient. However, the therapeutic application of either nuclear transfer or nuclear fusion of somatic cell has been hindered by technical complications as well as ethical objections. Recently, a new method is reported whereby ectopic expression of embryonic specific transcription factors was shown to induce fibroblasts to become embryonic like SCs (induced pluripotent stem cells. A major limitation of this method is the use of potentially harmful genome integrating viruses such as reto- or lentivirus. The main aim of this investigation was generation of human hematopoietic stem cells from induced fibroblasts by safe adenovectors carrying embryonically active genes. Material and Methods: Isolated fibroblasts from foreskin were expanded and recombinant adenoviruses carrying human Sox2, Oct4, Klf4, cMyc genes were added to culture. After formation of embryonic like colonies and cell expansion, they were transferred to embryonic media without bFGF, and embryoid bodies were cultured on stromal and non-stromal differentiation media for 14 days. Results: Expression of CD34 gene and antigenic markers, CD34, CD38 & CD133 in stromal culture showed significant difference with non-differentiation and non-stromal media. Conclusion: These findings show high hematopoietic differentiation rate of Adeno-iPS cells in stromal culture and no need to use growth factors. While, there was no difference between non-differentiation and non-stromal media.

Extra-anatomic transplantations in autologous adult cell therapies aiding anatomical regeneration and physiological recovery – An insight and categorization

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Editorial

2015-12-01

stimuli (voluntary and lack propagation of action potentials. However, the skeletal myoblasts in vitro, expanded as patches, have aided the in situ regeneration of the dysfunctional myocardium by secreting relevant growth factors [3]. Similarly, the buccal mucosal epithelium which is an opaque tissue has been applied to regenerate the damaged corneal epithelium, which in contrast is a transparent tissue. Here the buccal mucosal epithelium has been found to replace directly the dysfunctional corneal epithelium to assist in its regeneration and the resumption of proper function [4]. Though the source of the cells taken for repair of cartilage and corneal epithelium are extra-anatomic, they belong to the same germ layer of developmental origin; skeletal myoblasts (source and cardiomyocytes (target both from the mesoderm while buccal mucosal epithelium (source and corneal epithelium (target are both from the ectoderm. Extra-anatomic cell therapies reported in the literature such as the transplantation of olfactory ensheathing cells in spinal cord injury [5] also fit into this association, as the cell source for the replacement and the target organ exist within the same germ layer of ectoderm, developmentally but separated regionally. All these exchanges, we propose, should be termed as “Intra-germ Extra-anatomic Cell Therapies” (IECT. We have come across two extra-anatomic cell therapies that have been reported in the literature, where cells of the source and target tissue have different embryonic origins. Firstly, the transplantation of in vitro expanded buccal mucosal epithelial cells to treat urethral strictures in the “BEES-HAUS” (Buccal Epithelium Expanded & encapsulated in Scaffold - Hybrid Approach to Urethral Stricture approach reported by Vaddi et al [6] and secondly the use of gingival fibroblasts to replace the lost dermal fibroblasts in cell therapy for facial anti-aging [7] by Ebisawa et al both fall under this category. The buccal mucosal epithelial

Transplantation of umbilical cord blood-derived cells for novel indications in regenerative therapy or immune modulation: a scoping review of clinical studies.

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Iafolla, Marco A J; Tay, Jason; Allan, David S

2014-01-01

Although used mainly for transplantation of hematopoietic stem cells in the treatment of blood disorders, umbilical cord blood (UCB)-based therapies are now being used increasingly for novel applications in nonhematopoietic diseases and as a form of cellular regenerative therapy or immune modulation. We performed a systematic scoping review by searching Medline, EMBASE, and the Cochrane Library for published articles, and we searched www.clinicaltrials.com and the World Health Organization International Clinical Trials Registry Platform to describe the breadth of published studies and ongoing clinical activity in umbilical cord-based cellular therapy for regenerative therapy and immune modulation. The most commonly published area of expertise in the use of UCB-derived cellular transplantation for novel indications is for neurological disorders and this remains the most active area of study in ongoing registered trials. An increasingly broad range of disorders, however, are reflected in ongoing registered trials, which suggests greater activity, interest, and investment in UCB-derived cellular therapy. Interestingly, adult patients compose the majority of patients reported in published reports and registered ongoing clinical studies continue to enroll predominantly adult subjects. Geographically, Asian countries appear most active in UCB-derived cellular therapy and our analysis of ongoing studies suggests this trend will likely continue. Regular assessment of published and ongoing activity in UCB transplantation for emerging novel indications will be critical for informing UCB banking establishments and funding agencies to guide changes in banking practices related to emerging trends in cell therapy. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

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Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

2012-11-01

Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

Stem Cell Therapies in Retinal Disorders

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Aakriti Garg

2017-02-01

Full Text Available Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients’ diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

[Transplantation-associated infections].

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Würzner, R

2004-01-01

Transplantation-associated infections are caused by an infected transplanted organ or the endogenic or exogenic environment of the recipient in a state of induced immunodeficiency. The best therapy would be to reconstitute the immunodeficiency, but this is usually impossible as it endangers the transplanted organ. Thus, a specific, standardised anti-infectious therapy is needed even in the absence of clearly identified micro-organisms [bacteria (in two thirds gram-positive rods), parasites (in central Europe predominantly Toxoplasma), fungi (especially Candida spp. or Aspergillus spp.) or viruses (such as Parvovirus B19 and Cytomegalovirus)]. Origins of infection (e.g., hygiene), types of infection (e.g., reactivation), typical localisations, diagnostic tools (e.g., blood cultures, antigenic tests, PCR, CT, advantages and disadvantages of antibody assays) and possible therapies are briefly discussed. The take home messages are to avoid economy measures in microbial diagnostics and to use CMV-seronegative donors whenever possible.

Dopamine Cell Transplantation for Parkinson’s Disease: The Importance of Controlled Clinical Trials

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Freed, Curt R.; Zhou, Wenbo; Breeze, Robert E.

2011-01-01

Transplantation of human fetal dopamine neurons into the brain of Parkinson’s disease patients started in the late 1980s, less than 10 years after experiments in rats showed that embryonic dopamine neurons from a narrow window of development are suitable for transplantation. For human transplantation, the critical stage of development is 6 to 8 weeks after conception. Because putamen is the basal ganglia structure most depleted of dopamine in Parkinson’s disease and because it is the structur...

Label-free separation of human embryonic stem cells (hESCs) and their cardiac derivatives using Raman spectroscopy

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Chan, J W; Lieu, D K; Huser, T R; Li, R A

2008-09-08

Self-renewable, pluripotent human embryonic stem cells (hESCs) can be differentiated into cardiomyocytes (CMs), providing an unlimited source of cells for transplantation therapies. However, unlike certain cell lineages such as hematopoietic cells, CMs lack specific surface markers for convenient identification, physical separation, and enrichment. Identification by immunostaining of cardiac-specific proteins such as troponin requires permeabilization, which renders the cells unviable and non-recoverable. Ectopic expression of a reporter protein under the transcriptional control of a heart-specific promoter for identifying hESC-derived CMs (hESC-CMs) is useful for research but complicates potential clinical applications. The practical detection and removal of undifferentiated hESCs in a graft, which may lead to tumors, is also critical. Here, we demonstrate a non-destructive, label-free optical method based on Raman scattering to interrogate the intrinsic biochemical signatures of individual hESCs and their cardiac derivatives, allowing cells to be identified and classified. By combining the Raman spectroscopic data with multivariate statistical analysis, our results indicate that hESCs, human fetal left ventricular CMs, and hESC-CMs can be identified by their intrinsic biochemical characteristics with an accuracy of 96%, 98% and 66%, respectively. The present study lays the groundwork for developing a systematic and automated method for the non-invasive and label-free sorting of (i) high-quality hESCs for expansion, and (ii) ex vivo CMs (derived from embryonic or adult stem cells) for cell-based heart therapies.

Integration and long distance axonal regeneration in the central nervous system from transplanted primitive neural stem cells.

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Zhao, Jiagang; Sun, Woong; Cho, Hyo Min; Ouyang, Hong; Li, Wenlin; Lin, Ying; Do, Jiun; Zhang, Liangfang; Ding, Sheng; Liu, Yizhi; Lu, Paul; Zhang, Kang

2013-01-04

Spinal cord injury (SCI) results in devastating motor and sensory deficits secondary to disrupted neuronal circuits and poor regenerative potential. Efforts to promote regeneration through cell extrinsic and intrinsic manipulations have met with limited success. Stem cells represent an as yet unrealized therapy in SCI. Recently, we identified novel culture methods to induce and maintain primitive neural stem cells (pNSCs) from human embryonic stem cells. We tested whether transplanted human pNSCs can integrate into the CNS of the developing chick neural tube and injured adult rat spinal cord. Following injection of pNSCs into the developing chick CNS, pNSCs integrated into the dorsal aspects of the neural tube, forming cell clusters that spontaneously differentiated into neurons. Furthermore, following transplantation of pNSCs into the lesioned rat spinal cord, grafted pNSCs survived, differentiated into neurons, and extended long distance axons through the scar tissue at the graft-host interface and into the host spinal cord to form terminal-like structures near host spinal neurons. Together, these findings suggest that pNSCs derived from human embryonic stem cells differentiate into neuronal cell types with the potential to extend axons that associate with circuits of the CNS and, more importantly, provide new insights into CNS integration and axonal regeneration, offering hope for repair in SCI.

Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

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Shinichi Matsumoto

2011-06-01

Full Text Available Islet cell transplantation is categorized as a β-cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic islet cell transplantation is for the treatment of type 1 diabetes, and autologous islet cell transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic islet cell transplantation include poor efficacy of islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic islet cell transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor islet cell transplantation might alleviate the issue. Xeno-islet cell transplantation, β-cell regeneration from human stem cells and gene induction of the naïve pancreas represent the next generation of β-cell replacement therapy. Autologous islet cell transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous islet cell transplantation is an attractive option for hospitals performing total pancreatectomies without the proper islet isolation facilities.

Challenges in renal transplantation in Yemen.

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El-Nono, Ibrahiem H; Telha, Khaled A; Al-Alimy, Gamil M; Ghilan, Abdulilah M; Abu Asba, Nagieb W; Al-Zkri, Abdo M; Al-Adimi, Abdulilah M; Al-Ba'adani, Tawfiq H

2015-02-16

Background Renal replacement therapy was first introduced in Yemen in 1978 in the form of hemodialysis. Twenty years later, the first renal transplantation was performed. Kidney transplantations were started in socially and financially challenging circumstances in Yemen in 1998. A structured program was established and has been functioning regularly since 2005. A pediatric transplantation program was started in 2011. Material and Methods This was a prospective study of 181 transplants performed at the Urology and Nephrology Center between May 1998 and 2012. All transplants were from living related donors. The immunosuppressive protocol consisted initially of double therapy with steroid and mycophenolate mofetil (MMF). Subsequently, triple therapy with addition of a calcineurin inhibitor was introduced. Primary graft function was achieved in 176 (97.2%) recipients. Results Cold ischemia time was 48-68 min. Episodes of acute rejection in 12 patients were treated with high-dose steroids. Anti-thymocyte globulin (ATG) was used in cases of vascular or steroid-resistant rejection in 2 patients. The post-transplant complications, either surgical or medical, were comparable to those recorded in the literature. Conclusions Renal transplantation is a good achievement in our country. The patients and graft survival rates are comparable to other reports.

The Global Role of Kidney Transplantation

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Guillermo Garcia Garcia

2012-01-01

Full Text Available World Kidney Day on March 8 th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which, in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.

Human embryonic stem cell-derived pancreatic endoderm alleviates diabetic pathology and improves reproductive outcome in C57BL/KsJ-Lep(db/+) gestational diabetes mellitus mice.

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Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

2015-07-01

Gestational diabetes mellitus is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal maldevelopment. The cause of gestational diabetes mellitus can be attributed to both genetic and environmental factors, hence complicating its diagnosis and treatment. Pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice. In this study, we have developed a system of treating diabetes using human embryonic stem cell-derived pancreatic endoderm in a mouse model of gestational diabetes mellitus. Human embryonic stem cells were differentiated in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus. The transplant greatly improved glucose metabolism and reproductive outcome of the females compared with the control groups. Our findings support the feasibility of using differentiated human embryonic stem cells for treating gestational diabetes mellitus patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in-situ targeting of dendritic cells.

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Morelli, Adrian E; Thomson, Angus W

2014-08-01

Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCregs) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCregs (donor or recipient) and their mode of action, in-situ targeting of DCregs, and optimal therapeutic regimens to promote DCreg function. Recent studies have defined protocols and mechanisms whereby ex-vivo-generated DCregs of donor or recipient origin subvert allogeneic T-cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen is acquired, processed and presented by autologous dendritic cells, on the stability of DCregs, and on in-situ targeting of dendritic cells to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCregs in a clinically relevant nonhuman primate organ transplant model and production of clinical grade DCregs support early evaluation of DCreg therapy in human graft recipients. We discuss strategies currently used to promote dendritic cell tolerogenicity, including DCreg therapy and in-situ targeting of dendritic cells, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application.

[Hepatic cell transplantation: a new therapy in liver diseases].

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Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

2010-07-01

Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

Myogenic Precursors from iPS Cells for Skeletal Muscle Cell Replacement Therapy

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Isart Roca

2015-01-01

Full Text Available The use of adult myogenic stem cells as a cell therapy for skeletal muscle regeneration has been attempted for decades, with only moderate success. Myogenic progenitors (MP made from induced pluripotent stem cells (iPSCs are promising candidates for stem cell therapy to regenerate skeletal muscle since they allow allogenic transplantation, can be produced in large quantities, and, as compared to adult myoblasts, present more embryonic-like features and more proliferative capacity in vitro, which indicates a potential for more self-renewal and regenerative capacity in vivo. Different approaches have been described to make myogenic progenitors either by gene overexpression or by directed differentiation through culture conditions, and several myopathies have already been modeled using iPSC-MP. However, even though results in animal models have shown improvement from previous work with isolated adult myoblasts, major challenges regarding host response have to be addressed and clinically relevant transplantation protocols are lacking. Despite these challenges we are closer than we think to bringing iPSC-MP towards clinical use for treating human muscle disease and sporting injuries.

[Regulation of in vitro and in vivo differentiation of mouse embryonic stem cells, embryonic germ cells, and teratocarcinoma cells by TGFb family signaling factors].

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Gordeeva, O F; Nikonova, T M; Lifantseva, N V

2009-01-01

The activity of specific signaling and transcription factors determines the cell fate in normal development and in tumor transformation. The transcriptional profiles of gene-components of different branches of TGFbeta family signaling pathways were studied in experimental models of initial stages of three-dimensional in vitro differentiation of embryonic stem cells, embryonic germ cells and teratocarcinoma cells and in teratomas and teratocarcinomas developed after their transplantation into immunodeficient Nude mice. Gene profile analysis of studied cell systems have revealed that expression patterns of ActivinA, Nodal, Lefty1, Lefty2, TGF TGFbeta1, BMP4, and GDF were identical in pluripotent stem cells whereas the mRNAs of all examined genes with the exception of Inhibin betaA/ActivinA were detected in the teratocarcinoma cells. These results indicate that differential activity of signaling pathways of the TGFbeta family factors regulates pluripotent state maintenance and pluripotent stem cell differentiation into the progenitors of three germ layers and extraembryonic structures and that normal expression pattern of TGFbeta family factors is rearranged in embryonic teratocarcinoma cells during tumor growth in vitro and in vivo.

Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

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Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

2012-01-01

Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

Childhood Central Nervous System Embryonal Tumors Treatment (PDQ®)—Patient Version

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Childhood central nervous system embryonal tumors and pineal tumors are treated with surgery, radiation therapy, chemotherapy, high-dose chemotherapy with stem cell rescue and targeted therapy. Learn more in this expert-reviewed summary.

Growth in pediatric renal transplant recipients.

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Vasudevan, A; Phadke, K

2007-04-01

One of the fundamental challenges in managing pediatric renal transplant recipient is to ensure normal growth and development. The goal of renal transplant is not just to prolong life but to optimize quality of life. Short stature during childhood may be associated with academic underachievement and development of comorbidities such as attention deficit hyperactivity disorder, learning disability, and mood disorders. The most important factors affecting growth are use of corticosteroids, allograft function, and age and height deficit at the time of transplant. Aggressive conservative management of chronic renal failure and early use of growth hormone therapy will help in optimizing height at time of transplant. Early transplant, steroid minimization or withdrawal, and growth hormone therapy will help in achieving normal adult height in a majority of renal post transplant population. Steroid avoidance to achieve good growth still needs to be validated.

The cell cycle as a brake for β-cell regeneration from embryonic stem cells.

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El-Badawy, Ahmed; El-Badri, Nagwa

2016-01-13

The generation of insulin-producing β cells from stem cells in vitro provides a promising source of cells for cell transplantation therapy in diabetes. However, insulin-producing cells generated from human stem cells show deficiency in many functional characteristics compared with pancreatic β cells. Recent reports have shown molecular ties between the cell cycle and the differentiation mechanism of embryonic stem (ES) cells, assuming that cell fate decisions are controlled by the cell cycle machinery. Both β cells and ES cells possess unique cell cycle machinery yet with significant contrasts. In this review, we compare the cell cycle control mechanisms in both ES cells and β cells, and highlight the fundamental differences between pluripotent cells of embryonic origin and differentiated β cells. Through critical analysis of the differences of the cell cycle between these two cell types, we propose that the cell cycle of ES cells may act as a brake for β-cell regeneration. Based on these differences, we discuss the potential of modulating the cell cycle of ES cells for the large-scale generation of functionally mature β cells in vitro. Further understanding of the factors that modulate the ES cell cycle will lead to new approaches to enhance the production of functional mature insulin-producing cells, and yield a reliable system to generate bona fide β cells in vitro.

Genetic modification of hematopoietic stem cells: recent advances in the gene therapy of inherited diseases.

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Bueren, Juan A; Guenechea, Guillermo; Casado, José A; Lamana, María Luisa; Segovia, José C

2003-01-01

Hematopoietic stem cells constitute a rare population of precursor cells with remarkable properties for being used as targets in gene therapy protocols. The last years have been particularly productive both in the fields of gene therapy and stem cell biology. Results from ongoing clinical trials have shown the first unquestionable clinical benefits of immunodeficient patients transplanted with genetically modified autologous stem cells. On the other hand, severe side effects in a few patients treated with gene therapy have also been reported, indicating the usefulness of further improving the vectors currently used in gene therapy clinical trials. In the field of stem cell biology, evidence showing the plastic potential of adult hematopoietic stem cells and data indicating the multipotency of adult mesenchymal precursor cells have been presented. Also, the generation of embryonic stem cells by means of nuclear transfer techniques has appeared as a new methodology with direct implications in gene therapy.

Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

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Jack C. Reidling

2018-01-01

Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in situ targeting of dendritic cells

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Morelli, Adrian E.; Thomson, Angus W.

2014-01-01

Purpose of review Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCreg) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCreg (donor or recipient) and their mode of action, in situ targeting of DCreg, and optimal therapeutic regimens to promote DCreg function. Recent findings Recent studies have defined protocols and mechanisms whereby ex vivo-generated DCreg of donor or recipient origin subvert allogeneic T cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen (Ag) is acquired, processed and presented by autologous DCs, on the stability of DCreg, and on in situ targeting of DC to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCreg in a clinically-relevant non-human primate organ transplant model and production of clinical grade DCreg support early evaluation of DCreg therapy in human graft recipients. Summary We discuss strategies currently used to promote DC tolerogenicity, including DCreg therapy and in situ targeting of DC, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application. PMID:24926700

Radionuclide evaluation of renal transplants

International Nuclear Information System (INIS)

Yang Hong; Zhao Deshan

2000-01-01

Radionuclide renal imaging and plasma clearance methods can quickly quantitate renal blood flow and function in renal transplants. They can diagnose acute tubular necrosis and rejection, renal scar, surgical complications such as urine leaks, obstruction and renal artery stenosis after renal transplants. At the same time they can assess the therapy effect of renal transplant complications and can also predict renal transplant survival from early post-operative function studies

STEM CELL TRANSPLANTATION AS A POSSIBLE STRATEGY FOR TREATING STANDARD THERAPY-RESISTANT ANKYLOSING SPONDYLITIS

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I. Z. Gaidukova

2016-01-01

Full Text Available The authors have analyzed the literature dealing with studies of the efficiency and safety of stem cell transplantation (SCT in patients with ankylosing spondylitis (AS through the electronic resources Pubmed and Medline by using the keywords «bone marrow transplantation», «hematopoietic stem cell transplantation», «ankylosing spondylitis», «autoimmune diseases», and «sacroiliac joint biopsy». The paper describes four cases of SCT in AS patients, including transplantation that was carried out in one patient with lymphoma concurrent with AS, in two AS patients without blood cancers, and in one patient with AS concurrent with myeloid leukemia. Drug-free remission was achieved in 3 cases: lymphoma concurrent with AS (n=1, AS concurrent with myeloid leukemia (n=1, and AS without comorbidities (n=1. In addition to an improvement in the course of AS, there were also two cases with clinical presentations of AS after SCT. The given cases show that SCT can be basically used to induce drug-free remission in patients with severe forms of standard therapy-resistant AS. However, the introduction of SCT in clinical practice needs to adjust the technique to the specific features of AS patients. 

Paradoxical Reaction of Tuberculosis in a Heart Transplant Recipient During Antituberculosis Therapy: A Case Report.

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Wakamiya, A; Seguchi, O; Shionoiri, A; Kumai, Y; Kuroda, K; Nakajima, S; Yanase, M; Matsuda, S; Wada, K; Matsumoto, Y; Fukushima, S; Fujita, T; Kobayashi, J; Fukushima, N

2018-04-01

Tuberculous paradoxical reactions (PRs) are excessive immune reactions occurring after antituberculosis (TB) treatment and are commonly observed in immunocompromised hosts such as patients infected with the human immunodeficiency virus. We recently encountered a 63-year-old male heart transplant recipient who developed tuberculous PR after treatment for miliary TB. The patient had been receiving immunosuppressive therapy with cyclosporine and mycophenolate mofetil for over 15 years. The diagnosis of miliary TB was made based on the presence of intermittent fever and fatigue; thus, anti-TB treatments (isoniazid, levofloxacin, ethambutol, and pyrazinamide) were started, which led to rapid defervescence and regression of the granular shadow and pleural effusion. However, a new persistent fever and confused state developed 1 month after the anti-TB therapy was started. After excluding possible etiologies of the patient's symptom, a PR was suspected, and anti-TB drugs were continued; corticosteroids were added as anti-inflammatory agents. After that, he has shown a favorable course with long-term anti-TB chemotherapy. A PR should always be considered when the patients' symptoms of tuberculosis re-exacerbate after an appropriate anti-TB therapy. A PR commonly occurs in patients with various immunologic conditions including heart transplant recipients. Copyright © 2018 Elsevier Inc. All rights reserved.

Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors.

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Yang, Guanghua; Si-Tayeb, Karim; Corbineau, Sébastien; Vernet, Rémi; Gayon, Régis; Dianat, Noushin; Martinet, Clémence; Clay, Denis; Goulinet-Mainot, Sylvie; Tachdjian, Gérard; Tachdjian, Gérard; Burks, Deborah; Vallier, Ludovic; Bouillé, Pascale; Dubart-Kupperschmitt, Anne; Weber, Anne

2013-07-19

Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods. We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as α-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration. We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also for in vitro applications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.

Glycemia, Hypoglycemia, and Costs of Simultaneous Islet-Kidney or Islet After Kidney Transplantation Versus Intensive Insulin Therapy and Waiting List for Islet Transplantation.

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Gerber, Philipp A; Locher, Rebecca; Zuellig, Richard A; Tschopp, Oliver; Ajdler-Schaeffler, Evelyne; Kron, Philipp; Oberkofler, Christian; Brändle, Michael; Spinas, Giatgen A; Lehmann, Roger

2015-10-01

Long-term data of patients with type 1 diabetes mellitus (T1D) after simultaneous islet-kidney (SIK) or islet-after-kidney transplantation (IAK) are rare and have never been compared to intensified insulin therapy (IIT). Twenty-two patients with T1D and end-stage renal failure undergoing islet transplantation were compared to 70 patients matched for age and diabetes duration treated with IIT and to 13 patients with kidney transplantation alone or simultaneous pancreas-kidney after loss of pancreas function (waiting list for IAK [WLI]). Glycemic control, severe hypoglycemia, insulin requirement, and direct medical costs were analyzed. Glycated hemoglobin decreased significantly from 8.2 ± 1.5 to 6.7 ± 0.9% at the end of follow-up (mean 7.2 ± 2.5 years) in the SIK/IAK and remained constant in IIT (7.8 ± 1.0% and 7.6 ± 1.0) and WLI (7.8 ± 0.8 and 7.9 ± 1.0%). Daily insulin requirement decreased from 0.53 ± 0.15 to 0.29 ± 0.26 U/kg and remained constant in IIT (0.59 ± 0.19 and 0.58 ± 0.23 U/kg) and in WLI (0.76 ± 0.28 and 0.73 ± 0.11 U/kg). Severe hypoglycemia dropped in SIK/IAK from 4.5 ± 9.7 to 0.3 ± 0.7/patient-year and remained constant in IIT (0.1 ± 0.7 and 0.2 ± 0.8/patient-year). Detailed cost analysis revealed US $57,525 of additional cost for islet transplantation 5 years after transplantation. Based on a 5- and 10-year analysis, cost neutrality is assumed to be achieved 15 years after transplantation. This long-term cohort with more than 7 years of follow-up shows that glycemic control in patients with T1D after SIK/IAK transplantation improved, and the rate of severe hypoglycemia decreased significantly as compared to control groups. Cost analysis revealed that islet transplantation is estimated to be cost neutral at 15 years after transplantation.

Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

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Yoo EJ

2013-06-01

Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

Selection of patients for heart transplantation in the current era of heart failure therapy.

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Butler, Javed; Khadim, Ghazanfar; Paul, Kimberly M; Davis, Stacy F; Kronenberg, Marvin W; Chomsky, Don B; Pierson, Richard N; Wilson, John R

2004-03-03

We sought to assess the relationship between survival, peak exercise oxygen consumption (VO(2)), and heart failure survival score (HFSS) in the current era of heart failure (HF) therapy. Based on predicted survival, HF patients with peak VO(2) 14 ml/min/kg (p = 0.04). Of the patients with peak VO(2) of 10 to 14 ml/min/kg, 55% had low-risk HFSS and exhibited 88% one-year event-free survival. One-year survival after transplantation was 88%, which is similar to the 85% rate reported by the United Network for Organ Sharing for 1999 to 2000. Survival for HF patients in the current era has improved significantly, necessitating re-evaluation of the listing criteria for heart transplantation.

[The legal and ethical aspects of nerve tissue transplantation].

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Sramka, M; Rattaj, M

1992-01-01

The authors have specified the following criteria for the withdrawal of embryonal tissue at their department: 1) only tissue from dead fetus is allowed to be used in neurotransplantation; 2) embryonal tissue is to be obtained after spontaneous abortions from volunteers or from women asking for artificial abortion; 3) the women should be informed about the curative purposes of embryonal tissue voluntary donorship and they must give a written consent; 4) decision on abortion should be separated from the use of embryonal tissue; 5) women should not know recipients; no payments should be made for tissue; 6) the donor is not permitted to impregnate in order to use embryos for research or clinical purposes; 7) sampling of BWR, HBsAG, anti-HIV, cytomegalovirus, herpes I and II is to be made for serologic examinations and that from the cervix for cultivation and sensitivity, as well as ultrasound verification of a germinal age is done in potential donors; 8) consent should be signed to embryonal brain transplantation by recipient or his legitimate deputy if the recipient is certifiable. The above criteria should protect both the donor and the recipient. The use of embryonal tissue cultures seems to be promising. In addition to legal and ethic problems, immunological problems and problems concerning the aseptic withdrawal of embryonal tissue are falling off.

Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

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Xinxin Han

2017-01-01

Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

Kidney transplant in diabetic patients: modalities, indications and results

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Rangel Érika B

2009-08-01

Full Text Available Abstract Background Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy. Conclusion Type 1 and 2 diabetic patients present higher survival rates after transplant in comparison to the dialysis therapy, although the prevalence of cardiovascular events and infectious complications remain higher than in the general population.

The role of nanotechnology in induced pluripotent and embryonic stem cells research.

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Chen, Lukui; Qiu, Rong; Li, Lushen

2014-12-01

This paper reviews the recent studies on development of nanotechnology in the field of induced pluripotent and embryonic stem cells. Stem cell therapy is a promising therapy that can improve the quality of life for patients with refractory diseases. However, this option is limited by the scarcity of tissues, ethical problem, and tumorigenicity. Nanotechnology is another promising therapy that can be used to mimic the extracellular matrix, label the implanted cells, and also can be applied in the tissue engineering. In this review, we briefly introduce implementation of nanotechnology in induced pluripotent and embryonic stem cells research. Finally, the potential application of nanotechnology in tissue engineering and regenerative medicine is also discussed.

Comparative study of human embryonic stem cells (hESC and human induced pluripotent stem cells (hiPSC as a treatment for retinal dystrophies

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Marina Riera

2016-01-01

Full Text Available Retinal dystrophies (RD are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC-based therapies. We differentiated RPE from human embryonic stem cells (hESCs or human-induced pluripotent stem cells (hiPSCs and transplanted them into the subretinal space of the Royal College of Surgeons (RCS rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD.

Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies

Science.gov (United States)

Riera, Marina; Fontrodona, Laura; Albert, Silvia; Ramirez, Diana Mora; Seriola, Anna; Salas, Anna; Muñoz, Yolanda; Ramos, David; Villegas-Perez, Maria Paz; Zapata, Miguel Angel; Raya, Angel; Ruberte, Jesus; Veiga, Anna; Garcia-Arumi, Jose

2016-01-01

Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD. PMID:27006969

Era of liver transplantation: combined anatomic splenectomy and anticoagulant therapy in prevention of portal vein thrombosis after splenectomy.

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Hongwei, Chen; Zhang, Liang; Maoping, Li; Yong, Zhang; Chengyou, Du; Dewei, Li

2015-01-01

Portal vein thrombosis (PVT) is a common complication following splenectomy in patients with liver cirrhosis and portal hypertension, which also brings difficulties to future possible liver transplantation. This paper retrospectively analyzes the preventive effect of combined anatomic splenectomy and early anticoagulant therapy on post-splenectomy portal vein thrombosis in patients with portal hypertension. We retrospectively analyzed 136 patients who underwent splenectomy at our hospital between January 2010 and December 2013 due to liver cirrhosis and portal hypertension. Patient conditions, such as coagulation function, splenic and portal vein thrombosis, intra-abdominal hemorrhage, pancreatic leakage and intra-abdominal infections, are observed postoperatively. Despite the presence of liver cirrhosis and portal hypertension in patients, early postoperative anticoagulant therapy has no significant impact on coagulation function and intra-abdominal hemorrhage of these patients (p > 0.05). Anatomic splenectomy can reduce the occurrence of complications such as postoperative bleeding, pancreatic leakage and intra-abdominal infections (p splenectomy and early postoperative anticoagulant therapy can reduce post-splenectomy portal vein thrombosis in patients with portal hypertension, and is conducive to the future liver transplantation therapy may be needed by the patients.

Use of Renal Replacement Therapy May Influence Graft Outcomes following Liver Transplantation for Acute Liver Failure: A Propensity-Score Matched Population-Based Retrospective Cohort Study.

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Knight, Stephen R; Oniscu, Gabriel C; Devey, Luke; Simpson, Kenneth J; Wigmore, Stephen J; Harrison, Ewen M

2016-01-01

Acute kidney injury is associated with a poor prognosis in acute liver failure but little is known of outcomes in patients undergoing transplantation for acute liver failure who require renal replacement therapy. A retrospective analysis of the United Kingdom Transplant Registry was performed (1 January 2001-31 December 2011) with patient and graft survival determined using Kaplan-Meier methods. Cox proportional hazards models were used together with propensity-score based full matching on renal replacement therapy use. Three-year patient and graft survival for patients receiving renal replacement therapy were 77.7% and 72.6% compared with 85.1% and 79.4% for those not requiring renal replacement therapy (Prenal replacement therapy was a predictor of both patient death (hazard ratio (HR) 1.59, 95% CI 1.01-2.50, P = 0.044) but not graft loss (HR 1.39, 95% CI 0.92-2.10, P = 0.114). In groups fully matched on baseline covariates, those not receiving renal replacement therapy with a serum creatinine greater than 175 μmol/L had a significantly worse risk of graft failure than those receiving renal replacement therapy. In patients being transplanted for acute liver failure, use of renal replacement therapy is a strong predictor of patient death and graft loss. Those not receiving renal replacement therapy with an elevated serum creatinine may be at greater risk of early graft failure than those receiving renal replacement therapy. A low threshold for instituting renal replacement therapy may therefore be beneficial.

A novel approach to severe acute pancreatitis in sequential liver-kidney transplantation: the first report on the application of VAC therapy.

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Zanus, Giacomo; Boetto, Riccardo; D'Amico, Francesco; Gringeri, Enrico; Vitale, Alessandro; Carraro, Amedeo; Bassi, Domenico; Scopelliti, Michele; Bonsignore, Pasquale; Burra, Patrizia; Angeli, Paolo; Feltracco, Paolo; Cillo, Umberto

2011-03-01

This work is the first report of vacuum-assisted closure (VAC) therapy applied as a life-saving surgical treatment for severe acute pancreatitis occurring in a sequential liver- and kidney-transplanted patient who had percutaneous biliary drainage for obstructive "late-onset" jaundice. Surgical exploration with necrosectomy and sequential laparotomies was performed because of increasing intra-abdominal pressure with hemodynamic instability and intra-abdominal multidrug-resistant sepsis, with increasingly difficult abdominal closure. Repeated laparotomies with VAC therapy (applying a continuous negative abdominal pressure) enabled a progressive, successful abdominal decompression, with the clearance of infection and definitive abdominal wound closure. The application of a negative pressure is a novel approach to severe abdominal sepsis and laparostomy management with a view to preventing compartment syndrome and fatal sepsis, and it can lead to complete abdominal wound closure. © 2010 The Authors. Transplant International © 2010 European Society for Organ Transplantation.

Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies.

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Ho, V T; Revta, C; Richardson, P G

2008-02-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), remains one of the most serious and common complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the clinical triad of (1) painful hepatomegaly, (2) hyperbilirubinemia and (3) unexplained fluid retention. While milder cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide (DF), a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. Multiple studies, including a recent large international multicenter phase II clinical trial, have demonstrated 30-60% complete remission rates with DF, even among patients with severe VOD and multiorgan failure. This article will review our current understanding of hepatic VOD, and update the clinical trial experience with DF and other potential therapies for this feared transplant complication.

CNS embryonal tumours: WHO 2016 and beyond.

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Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

2018-02-01

Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

Combination of ablative fractional laser and daylight-mediated photodynamic therapy for actinic keratosis in organ transplant recipients – a randomized controlled trial

DEFF Research Database (Denmark)

Togsverd-Bo, Katrine; Lei, Ulrikke; Erlendsson, A M

2015-01-01

BACKGROUND: Topical photodynamic therapy (PDT) for actinic keratoses (AK) is hampered by pain during illumination and inferior efficacy in organ-transplant recipients (OTR). OBJECTIVES: We assessed ablative fractional laser (AFL)-assisted daylight photodynamic therapy (PDT) (AFL-dPDT) compared...

Hyperosmolar nonketotic hyperglycemic coma induced by methylprednisolone pulse therapy for acute rejection after liver transplantation: a case report and review of the literature

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Zhou J

2014-12-01

Full Text Available Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC is a serious, rare complication induced by methylprednisolone (MP pulse therapy for acute rejection after orthotopic liver transplantation (OLT. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment

Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party.

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Devillier, Raynier; Dalle, Jean-Hugues; Kulasekararaj, Austin; D'aveni, Maud; Clément, Laurence; Chybicka, Alicja; Vigouroux, Stéphane; Chevallier, Patrice; Koh, Mickey; Bertrand, Yves; Michallet, Mauricette; Zecca, Marco; Yakoub-Agha, Ibrahim; Cahn, Jean-Yves; Ljungman, Per; Bernard, Marc; Loiseau, Pascale; Dubois, Valérie; Maury, Sébastien; Socié, Gérard; Dufour, Carlo; Peffault de Latour, Regis

2016-07-01

Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; Paplastic anemia. Copyright© Ferrata Storti Foundation.

Immune System and Kidney Transplantation.

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Shrestha, Badri Man

2017-01-01

The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

Role of SDF1/CXCR4 Interaction in Experimental Hemiplegic Models with Neural Cell Transplantation

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Noboru Suzuki

2012-02-01

Full Text Available Much attention has been focused on neural cell transplantation because of its promising clinical applications. We have reported that embryonic stem (ES cell derived neural stem/progenitor cell transplantation significantly improved motor functions in a hemiplegic mouse model. It is important to understand the molecular mechanisms governing neural regeneration of the damaged motor cortex after the transplantation. Recent investigations disclosed that chemokines participated in the regulation of migration and maturation of neural cell grafts. In this review, we summarize the involvement of inflammatory chemokines including stromal cell derived factor 1 (SDF1 in neural regeneration after ES cell derived neural stem/progenitor cell transplantation in mouse stroke models.

Impact of fixed pulmonary hypertension on post-heart transplant outcomes in bridge-to-transplant patients

DEFF Research Database (Denmark)

Alba, Ana Carolina; Rao, Vivek; Ross, Heather J

2010-01-01

Fixed pulmonary hypertension (FPH) is considered a contraindication to cardiac transplantation. Ventricular assist device (VAD) therapy through prolonged left ventricular unloading may reverse FPH. Our aim was to assess post-transplant outcomes and survival in patients with and without FPH...

Fetal frontal cortex transplant (14C) 2-deoxyglucose uptake and histology: survival in cavities of host rat brain motor cortex

International Nuclear Information System (INIS)

Sharp, F.R.; Gonzalez, M.F.

1984-01-01

Fetal frontal neocortex from 18-day-old rat embryonic brain was transplanted into cavities in 30-day-old host motor cortex. Sixty days after transplantation, 5 of 15 transplanted rats had surviving fetal transplants. The fetal cortex transplants were physically attached to the host brain, completely filled the original cavity, and had numerous surviving cells including pyramidal neurons. Cell lamination within the fetal transplant was abnormal. The ( 14 C) 2-deoxyglucose uptake of all five of the fetal neocortex transplants was less than adjacent cortex and contralateral host motor-sensory cortex, but more than adjacent corpus callosum white matter. The results indicate that fetal frontal neocortex can be transplanted into damaged rat motor cortex. The metabolic rate of the transplants suggests they could be partially functional

Graphene for enhanced embryonic stem cell photo-transfection efficiency

CSIR Research Space (South Africa)

Mthunzi, P

2013-04-01

Full Text Available Due to their pluripotency properties, embryonic stem (ES) cells possess great potential in regenerative therapy. Since reported a promising tissue engineering scaffold material, here, graphene is demonstrated to significantly improve the ES cell...

Islet alloautotransplantation: Allogeneic pancreas transplantation followed by transplant pancreatectomy and islet transplantation.

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Nijhoff, M F; Dubbeld, J; van Erkel, A R; van der Boog, P J M; Rabelink, T J; Engelse, M A; de Koning, E J P

2018-04-01

Simultaneous pancreas-kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD). Due to complications, in up to 10% of patients, allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here, we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had undergone SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft, and almost 480 000 islet equivalents were infused into the portal vein. The patient recovered fully. After 3 months, near-normal mixed meal test (fasting glucose 7.0 mmol/L, 2-hour glucose 7.5 mmol/L, maximal stimulated C-peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. Glycated hemoglobin while taking a low dose of long-acting insulin was 32.7 mmol/mol hemoglobin (5.3%). When a donor pancreas is lost after transplantation, rescue β cell therapy by islet alloautotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA alloantigen exposure. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Simultaneous splenectomy during liver transplantation augments anti-viral therapy in patients infected with hepatitis C virus.

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Chu, Heng-Cheng; Hsieh, Chung-Bao; Hsu, Kuo-Feng; Fan, Hsiu-Lung; Hsieh, Tsai-Yuan; Chen, Teng-Wei

2015-01-01

Simultaneous splenectomy in liver transplantation (LT) is selectively indicated because of splenoportal venous thromboses and increased sepsis. Therefore, its impact should be further investigated. Of the 160 liver transplant patients, only 40 underwent simultaneous splenectomy. Clinicopathologic characteristics and outcomes were compared between the splenectomy and non-splenectomy group using retrospective analysis. Although the groups were similar and had no significant difference in the intra- and postoperative data, non-splenectomy group had more male patients. However, splenectomy group showed significantly higher platelet and leukocyte counts at 1 month and 6 months after the transplantation and higher hepatitis C virus anti-viral therapy completion. Furthermore, 3 patients developed portal or splenic vein thrombosis during the postoperative follow-up, but the overall survival rate did not significantly differ between these groups. Simultaneous splenectomy in LT can be safely performed, particularly in patients with hepatitis C virus cirrhosis, small-for-size grafts, hypersplenism, and ABO blood group incompatible (ABO - incompatible) LT. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypercholesterolemia in Renal Transplant Recipients; contributing Factors, Effect of Dietary Modification and Fluvastatin Therapy

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Rahed Awad

1999-01-01

Full Text Available Hypercholesterolemia which frequently follows renal transplantation, places kidney graft recipients at an increased risk for atherosclerosis and cardiovascular diseases. We attempt in this study to determine the prevalence, and evaluate severity and treatment of hypercholesterolemia in kidney transplant recipients. We studied 78 renal transplant patients with a mean age of 42.1 years and mean transplant duration of 6.2 years (range from six months to 8.5 years. They were on triple immunosuppressive therapy and had serum creatinine level of less than 160µmol/L. Thirty-one patients (39.8% were found to have blood cholesterol levels > 6.4 mmol/L. Significant positive correlation was found between hypercholesterolemia and cyclosporine blood levels above 200 ng/ml (p< 0.0009. Furthermore, proteinuria positively correlated with hypercholesterolemia (p< 0.0006. There was no significant correlation between cholesterol blood level and the patient age, sex, presence of diabetes, prednisolone, dose, or treatment with C.-blockers and diuretics. Dietary modification was not effective in reducing the blood cholesterol level in our patients, so we used fluvastatin in a dose of 20 to 40 mg daily for a period of three months. This drug was effective in lowering the mean cholesterol blood levels from 7.1 to 5.2 mmol/L (p< 0.005. One out of 19-electromyogram studies showed abnormal pattern. We did not notice change in the levels of creatinine phosphokinase, serum creatinine or lover enzymes. In conclusion, hyper-cholesterolemia is common in stable renal transplant patients. The presence of proteinuria and the high level of blood cyclosporine are significantly associated with hypercholesterolemia. Low-dose fluvastatin was well-tolerated and effective cholesterol lowering treatment.

Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

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Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

2007-01-01

Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

Everolimus in Heart Transplantation: An Update

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Stephan W. Hirt

2013-01-01

Full Text Available The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.

Viral infections in transplant recipients.

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Razonable, R R; Eid, A J

2009-12-01

Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

[Defibrotide therapy for patients with sinusoidal obstruction syndrome after hematopoietic stem cell transplantation].

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Yakushijin, Kimikazu; Okamura, Atsuo; Ono, Kanako; Kawano, Yuko; Kawano, Hiroki; Funakoshi, Yohei; Kawamori, Yuriko; Nishikawa, Shinichiro; Minagawa, Kentaro; Sada, Akiko; Shimoyama, Manabu; Yamamoto, Katsuya; Katayama, Yoshio; Matsui, Toshimitsu

2009-01-01

Sinusoidal obstruction syndrome (SOS) is one of the life-threatening complications caused by endothelial damage to the hepatic sinusoids after hematopoietic stem cell transplantation. However, a satisfactory treatment for SOS has not yet been established. Defibrotide has anti-thrombotic, anti-ischemic, anti-inflammatory, and thrombolytic properties without systemic anticoagulant effects. We treated eight post-transplant SOS patients with defibrotide. Three patients responded to the therapy and the initial response was observed within a week. In addition to the improvement of liver function, rapid recovery of response to diuretic drugs followed by the improvement of renal function was observed. All of the five patients with respiratory dysfunction died despite administration of defibrotide, suggesting that early treatment might lead to better outcomes. There were no severe adverse effects directly due to defibrotide administration. Defibrotide seems to be a promising treatment for SOS, and the initiation of a clinical study in Japan would be important.

Stem cell therapy in spinal cord injury: Hollow promise or promising science?

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Aimee Goel

2016-01-01

Full Text Available Spinal cord injury (SCI remains one of the most physically, psychologically and socially debilitating conditions worldwide. While rehabilitation measures may help limit disability to some extent, there is no effective primary treatment yet available. The efficacy of stem cells as a primary therapeutic option in spinal cord injury is currently an area under much scrutiny and debate. Several laboratory and some primary clinical studies into the use of bone marrow mesenchymal stem cells or embryonic stem cell-derived oligodentrocyte precursor cells have shown some promising results in terms of remyelination and regeneration of damaged spinal nerve tracts. More recently,laboratory and early clinical experiments into the use of Olfactory Ensheathing Cells, a type of glial cell derived from olfactory bulb and mucosa have provided some phenomenal preliminary evidence as to their neuroregenerative and neural bridging capacity. This report compares and evaluates some current research into selected forms of embryonic and mesenchymal stem cell therapy as well as olfactory ensheathing cell therapy in SCI, and also highlights some legal and ethical issues surrounding their use. While early results shows promise, more rigorous large scaleclinical trials are needed to shed light on the safety, efficacy and long term viability of stem cell and cellular transplant techniques in SCI.

Stem Cell-Based Therapies for Ischemic Stroke

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Lei Hao

2014-01-01

Full Text Available In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs, inducible pluripotent stem cells (iPSCs, neural stem cells (NSCs, and mesenchymal stem cell (MSCs might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.

Bioengineering in renal transplantation: technological advances and novel options.

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Yeo, Wee-Song; Zhang, Yao-Chun

2017-06-06

End-stage kidney disease (ESKD) is one of the most prevalent diseases in the world with significant morbidity and mortality. Current modes of renal replacement therapy include dialysis and renal transplantation. Although dialysis is an acceptable mode of renal replacement therapy, it does have its shortcomings, which include poorer life expectancy compared with renal transplantation, risk of infections and vascular thrombosis, lack of vascular access and absence of biosynthetic functions of the kidney. Renal transplantation, in contrast, is the preferred option of renal replacement therapy, with improved morbidity and mortality rates and quality of life, compared with dialysis. Renal transplantation, however, may not be available to all patients with ESKD. Some of the key factors limiting the availability and efficiency of renal transplantation include shortage of donor organs and the constant risk of rejection with complications associated with over-immunosuppression respectively. This review focuses chiefly on the potential roles of bioengineering in overcoming limitations in renal transplantation via the development of cell-based bioartificial dialysis devices as bridging options before renal transplantation, and the development of new sources of organs utilizing cell and organ engineering.

Sporotrichosis in Renal Transplant Patients

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Paulo Gewehr

2013-01-01

Full Text Available The current report describes two renal transplant recipients who presented with sporotrichosis. In addition, the authors review the general aspects of sporotrichosis in renal transplant recipients reported in the literature. Sporotrichosis is a rare fungal infection in transplant patients and has been reported primarily in renal transplant recipients not treated with antifungal prophylaxis. Extracutaneous forms of sporotrichosis without skin manifestations and no previous history of traumatic injuries have been described in such patients and are difficult to diagnose. Renal transplant recipients with sporotrichosis described in the present report were successfully treated with antifungal therapy including amphotericin B deoxycholate, lipid amphotericin B formulations, fluconazole and itraconazole.

From gristle to chondrocyte transplantation: treatment of cartilage injuries.

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Lindahl, Anders

2015-10-19

This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. © 2015 The Author(s).

From gristle to chondrocyte transplantation: treatment of cartilage injuries

Science.gov (United States)

Lindahl, Anders

2015-01-01

This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. PMID:26416680

Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation.

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Andreoli, Maria Claudia Cruz; Souza, Nádia Karina Guimarães de; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Coelho, Maria Paula Vilela; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; Almeida, Marcio Dias de; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; Santos, Oscar Pavão Dos; Santos, Bento Cardoso Dos

2017-01-01

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (prenal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability

Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

Science.gov (United States)

Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

2017-10-01

One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

Anti-troponin I antibodies in renal transplant patients.

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Nunes, José Pedro L; Sampaio, Susana; Cerqueira, Ana; Kaya, Ziya; Oliveira, Nuno Pardal

2015-02-01

To characterize the prevalence and clinical correlates of anti-troponin I antibodies in renal transplant patients. A group of 48 consecutive renal transplant patients under immunosuppressive therapy were studied. Anti-troponin I antibodies were measured and clinical data were retrieved. An anti-troponin I antibody titer renal transplant patients, and are not associated with the presence of clinical heart disease, but are associated with lack of statin therapy. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Stem Cell Transplants in Cancer Treatment

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Stem cell transplants are procedures that restore blood-forming stem cells in cancer patients who have had theirs destroyed by very high doses of chemotherapy or radiation therapy. Learn about the types of transplants and side effects that may occur.

Recombinant human laminin isoforms can support the undifferentiated growth of human embryonic stem cells

International Nuclear Information System (INIS)

Miyazaki, Takamichi; Futaki, Sugiko; Hasegawa, Kouichi; Kawasaki, Miwa; Sanzen, Noriko; Hayashi, Maria; Kawase, Eihachiro; Sekiguchi, Kiyotoshi; Nakatsuji, Norio; Suemori, Hirofumi

2008-01-01

Human embryonic stem cells (hESCs) are thought to be a promising cell source for cell transplantation therapy. For such a clinical application, the hESCs should be manipulated using appropriate and qualified materials. In this study, we examined the efficacy of recombinant human laminin (rhLM) isoforms on the undifferentiated growth of hESCs. We first determined the major integrins expressed on the hESCs to reveal the preference of the hESCs for rhLMs, and found that the hESCs mainly expressed integrin α6β1, which binds predominantly to laminin-111, -332 and -511/-521. When the hESCs were seeded onto rhLMs, the cells indeed adhered markedly to rhLM-332, and to rhLM-511 and rhLM-111 to a lesser extent. The hESCs proliferated on these three rhLMs for several passages while preserving their pluripotency. These results show that rhLM-111, -332, and -511 are good substrates to expand undifferentiated hESCs due to their high affinity to integrin α6β1 expressed on hESCs

Early conversion from calcineurin inhibitor- to everolimus-based therapy following kidney transplantation : Results of the randomized ELEVATE trial

NARCIS (Netherlands)

de Fijter, Johan W; Holdaas, Hallvard; Øyen, Ole; Sanders, Jan Stephan; Sundar, Sankaran; Bemelman, Frederike J; Sommerer, Claudia; Pascual, Julio; Avihingsanon, Yingyos; Pongskul, Cholatip; Oppenheimer, Frederic; Toselli, Lorenzo; Russ, Graeme; Wang, Zailong; Lopez, Patricia; Kochuparampil, Jossy; Cruzado, Josep M; van der Giet, Markus

In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and

Transplantation of rat embryonic stem cell-derived retinal progenitor cells preserves the retinal structure and function in rat retinal degeneration.

Science.gov (United States)

Qu, Zepeng; Guan, Yuan; Cui, Lu; Song, Jian; Gu, Junjie; Zhao, Hanzhi; Xu, Lei; Lu, Lixia; Jin, Ying; Xu, Guo-Tong

2015-11-09

Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we aimed to generate retinal progenitor cells (RPCs) from rat ESCs (rESCs) and to test their therapeutic effects in rat model. The rESCs (DA8-16) were cultured in N2B27 medium with 2i, and differentiated to two types of RPCs following the SFEBq method with modifications. For rESC-RPC1, the cells were switched to adherent culture at D10, while for rESC-RPC2, the suspension culture was maintained to D14. Both RPCs were harvested at D16. Primary RPCs were obtained from P1 SD rats, and some of them were labeled with EGFP by infection with lentivirus. To generate Rax::EGFP knock-in rESC lines, TALENs were engineered to facilitate homologous recombination in rESCs, which were cotransfected with the targeting vector and TALEN vectors. The differentiated cells were analyzed with live image, immunofluorescence staining, flow cytometric analysis, gene expression microarray, etc. RCS rats were used to mimic the degeneration of retina and test the therapeutic effects of subretinally transplanted donor cells. The structure and function of retina were examined. We established two protocols through which two types of rESC-derived RPCs were obtained and both contained committed retina lineage cells and some neural progenitor cells (NPCs). These rESC-derived RPCs survived in the host retinas of RCS rats and protected the retinal structure and function in early stage following the transplantation. However, the glia enriched rESC-RPC1 obtained through early and longer adherent culture only increased the b-wave amplitude at 4 weeks, while the longer suspension culture gave rise to evidently neuronal differentiation in rESC-RPC2 which significantly improved the visual function of RCS rats. We have successfully differentiated

Radioimmunotherapy of indolent non-Hodgkin's lymphoma with Yttrium-90 labeled anti-CD20 monoclonal antibody therapy does not preclude subsequent chemotherapy or autologous hematologic stem cell transplantation therapy in most patients

International Nuclear Information System (INIS)

Wiseman, G.A.; Witzig, T.E.; Ansell, S.M.; Ristow, K.M.

2002-01-01

Introduction: Yttrium-90 (Y-90) labeled anti-CD20 monoclonal antibody (ibritumomab tiuxetan or Zevalin TM ) is a novel therapy for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (NHL). Patients treated with Zevalin radioimmunotherapy (RIT) are limited from higher doses due to transient and reversible platelet and neutrophil suppression. Patients with indolent NHL who relapse or are refractory to chemotherapy have a 70-80% overall response rate and a 20-30% complete response rate when treated with Zevalin RIT. Therefore additional treatment is required in a minority of patients shortly after Zevalin therapy and in many others at relapse. Relapsed patients are generally treated with chemotherapy alone or high dose chemotherapy followed by autologous transplantation. We wanted to evaluate the ability of patients to tolerate subsequent therapy given at relapse following Zevalin RIT. Methods: We had 58 patients who relapsed after receiving Zevalin RIT and later received additional therapy. The clinical records and lab results were reviewed and compared with a matched control group of patients treated prior to Zevalin availability who received chemotherapy without prior Zevalin RIT. Results: The toxicity in 58 patients treated with Zevalin RIT and subsequent therapy was not significantly different from the control group who did not receive Zevalin RIT. Patients had a median of two subsequent therapies (range, 1-7) after Zevalin. Twenty eight percent required blood cell growth factor support with subsequent chemotherapy and 2 patients required reductions from the standard chemotherapy doses due to prolonged myelosuppression. Eight patients subsequently had successful autologous hematologic stem cell transplant with cells collected after Zevalin. Thirteen of the 58 patients (28%) treated with standard dose chemotherapy were hospitalized for neutropenic fever or thrombocytopenia. Conclusions: Chemotherapy or high dose chemotherapy with autologous transplantation

Normal cholesterol levels with lovastatin (Mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation

International Nuclear Information System (INIS)

East, C.; Grundy, S.M.; Bilheimer, D.W.

1986-01-01

Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia

Budget impact analysis of conversion from cyclosporine to sirolimus as immunosuppressive medication in renal transplantation therapy

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Foroutan N

2013-10-01

Full Text Available Naghmeh Foroutan,1 Hamid R Rasekh,1 Jamshid Salamzadeh,1 Hamid R Jamshidi,1 Mohsen Nafar2 1Department of Pharmacoeconomics and Pharmaceutical Management, School of Pharmacy, Shahid Beheshti University of Medical Sciences, 2Department of Kidney Transplantation, Urinary Nephrology Research Center (UNRC, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Objectives: The aim of this study was to determine budget impact of conversion from cyclosporine (CsA to sirolimus (SRL in renal transplant therapy (RTT from the perspective of insurance organizations in Iran. Methods: An Excel-based model was developed to determine cost of RTT, comparing current CsA based therapy to an mTOR inhibitor-based therapy regimen. Total cost included both cost of immunosuppressive agents and relative adverse events. The inputs were derived from database of Ministry of Health and insurance organizations, hospital and pharmacy based registries, and available literature that were varied through a one-way sensitivity analysis. According to the model, there were almost 17,000 patients receiving RTT in Iran, out of which about 2,200 patients underwent the operation within the study year. The model was constructed based on the results of a local RCT, in which test and control groups received CsA, SRL, and steroids over the first 3 months posttransplantation and, from the fourth month on, CsA, mycophenolate mofetil (MMF, and steroids were used in the CsA group and SRL, MMF, and steroids were administered in the SRL group, respectively. Results: The estimated cost of RTT with CsA was US$4,850,000 versus US$4,300,000 receiving SRL. These costs corresponded to the cost saving of almost US$550,000 for the payers. Conclusion: To evaluate the financial consequence of adding mTOR inhibitors to the insurers’ formulary, in the present study, a budget impact analysis was conducted on sirolimus. Fewer cases of costly adverse events along with

Pancreas transplants

International Nuclear Information System (INIS)

Chandra, J.; Phillips, R.R.; Boardman, P.; Gleeson, F.V.; Anderson, E.M.

2009-01-01

Cadaveric, whole pancreas transplantation has proved an effective therapy in the treatment of long-standing type 1 diabetes mellitus and is capable of achieving an insulin-independent eugyclaemic state. As a result, this procedure is being increasingly performed. However, the surgical procedure is complex and unfamiliar to many radiologists. Imaging with computed tomography (CT) and magnetic resonance imaging (MRI) gives excellent results and can be used confidently to diagnose vascular, enteric, and immune-mediated complications. We present a review of the normal post-transplantation appearance and the features of early and late complications.

Pancreas transplants

Energy Technology Data Exchange (ETDEWEB)

Chandra, J.; Phillips, R.R.; Boardman, P.; Gleeson, F.V. [Department of Radiology, Churchill Hospital, Headington, Oxford (United Kingdom); Anderson, E.M. [Department of Radiology, Churchill Hospital, Headington, Oxford (United Kingdom)], E-mail: ewan.anderson@orh.nhs.uk

2009-07-15

Cadaveric, whole pancreas transplantation has proved an effective therapy in the treatment of long-standing type 1 diabetes mellitus and is capable of achieving an insulin-independent eugyclaemic state. As a result, this procedure is being increasingly performed. However, the surgical procedure is complex and unfamiliar to many radiologists. Imaging with computed tomography (CT) and magnetic resonance imaging (MRI) gives excellent results and can be used confidently to diagnose vascular, enteric, and immune-mediated complications. We present a review of the normal post-transplantation appearance and the features of early and late complications.

Combination of low-energy shock-wave therapy and bone marrow mesenchymal stem cell transplantation to improve the erectile function of diabetic rats.

Science.gov (United States)

Shan, Hai-Tao; Zhang, Hai-Bo; Chen, Wen-Tao; Chen, Feng-Zhi; Wang, Tao; Luo, Jin-Tai; Yue, Min; Lin, Ji-Hong; Wei, An-Yang

2017-01-01

Stem cell transplantation and low-energy shock-wave therapy (LESWT) have emerged as potential and effective treatment protocols for diabetic erectile dysfunction. During the tracking of transplanted stem cells in diabetic erectile dysfunction models, the number of visible stem cells was rather low and decreased quickly. LESWT could recruit endogenous stem cells to the cavernous body and improve the microenvironment in diabetic cavernous tissue. Thus, we deduced that LESWT might benefit transplanted stem cell survival and improve the effects of stem cell transplantation. In this research, 42 streptozotocin-induced diabetic rats were randomized into four groups: the diabetic group (n = 6), the LESWT group (n = 6), the bone marrow-derived mesenchymal stem cell (BMSC) transplantation group (n = 15), and the combination of LESWT and BMSC transplantation group (n = 15). One and three days after BMSC transplantation, three rats were randomly chosen to observe the survival numbers of BMSCs in the cavernous body. Four weeks after BMSC transplantation, the following parameters were assessed: the surviving number of transplanted BMSCs in the cavernous tissue, erectile function, real-time polymerase chain reaction, and penile immunohistochemical assessment. Our research found that LESWT favored the survival of transplanted BMSCs in the cavernous body, which might be related to increased stromal cell-derived factor-1 expression and the enhancement of angiogenesis in the diabetic cavernous tissue. The combination of LESWT and BMSC transplantation could improve the erectile function of diabetic erectile function rats more effectively than LESWT or BMSC transplantation performed alone.

Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines.

Science.gov (United States)

Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

2010-06-01

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi-organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis.

Science.gov (United States)

Casulo, Carla; Friedberg, Jonathan W; Ahn, Kwang W; Flowers, Christopher; DiGilio, Alyssa; Smith, Sonali M; Ahmed, Sairah; Inwards, David; Aljurf, Mahmoud; Chen, Andy I; Choe, Hannah; Cohen, Jonathon; Copelan, Edward; Farooq, Umar; Fenske, Timothy S; Freytes, Cesar; Gaballa, Sameh; Ganguly, Siddhartha; Jethava, Yogesh; Kamble, Rammurti T; Kenkre, Vaishalee P; Lazarus, Hillard; Lazaryan, Aleksandr; Olsson, Richard F; Rezvani, Andrew R; Rizzieri, David; Seo, Sachiko; Shah, Gunjan L; Shah, Nina; Solh, Melham; Sureda, Anna; William, Basem; Cumpston, Aaron; Zelenetz, Andrew D; Link, Brian K; Hamadani, Mehdi

2017-12-11

Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within 2 years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup. ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within 2 years of frontline chemoimmunotherapy. We identified 2 groups: the non-autoHCT cohort (patients from the NLCS with ETF not undergoing autoHCT) and the autoHCT cohort (CIBMTR patients with ETF undergoing autoHCT). All patients received rituximab-based chemotherapy as frontline treatment; 174 non-autoHCT patients and 175 autoHCT patients were identified and analyzed. There was no difference in 5-year OS between the 2 groups (60% versus 67%, respectively; P = .16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5-year OS than those without autoHCT (73% versus 60%, P = .05). On multivariate analysis, early use of autoHCT was associated with significantly reduced mortality (hazard ratio, .63; 95% confidence interval, .42 to .94; P = .02). Patients with FL experiencing ETF after frontline chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in select FL patients experiencing ETF. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Expanding the indications of pancreas transplantation alone.

Science.gov (United States)

Mehrabi, Arianeb; Golriz, Mohammad; Adili-Aghdam, Fatemeh; Hafezi, Mohammadreza; Ashrafi, Maryam; Morath, Christian; Zeier, Martin; Hackert, Thilo; Schemmer, Peter

2014-11-01

Total pancreatectomy (TP) is associated with postoperative endocrine and exocrine insufficiency. Especially, insulin therapy reduces quality of life and may lead to long-term complications. We review the literature with regard to the potential option of pancreas transplantation alone (PTA) after TP in patients with chronic pancreatitis or benign tumors. A MEDLINE search (1958-2013) using the terminologies pancreas transplantation, pancreas transplantation alone, total pancreatectomy, morbidity, mortality, insulin therapy, and quality of life was performed. In addition, the current book and congress publications were reviewed. Total pancreatectomy after benign and borderline tumors as well as chronic pancreatitis is continuously increasing. Despite improvement of exogenous insulin therapy, more than 50% of these patients experience severe glucose control problems, which cause up to 50% long-term mortality. Pancreas transplantation alone can cure both endocrine and exocrine insufficiency and reduce the associated risks. The 3-year graft and patient survival rates after PTA are up to 73% and 100%, respectively. Pancreas transplantation alone after TP in patients with pancreatitis or benign tumors improves the recipient's quality of life and reduces long-term mortality. Considering the amount of available organs and potential candidates, PTA can be a treatment option for patients after TP with chronic pancreatitis or benign tumors.

Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

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Elena Crespo

Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

Bone marrow transplantation and other treatment after radiation injury

International Nuclear Information System (INIS)

Balner, H.

1977-01-01

This review deals mainly with current concepts about bone marrow transplantation as therapy for serious radiation injury. Such injury can be classified according to the following broadly defined dose ranges: (1) the supralethal range, leading mainly to the cerebral and intestinal syndromes; (2) the potentially lethal or therapeutic range which causes the bone marrow syndrome, and (3) the sublethal range which rarely leads to injury requiring therapy. The bone marrow syndrome of man and animals is discussed in detail. The optimal therapy for this syndrome is bone marrow transplantation in conjunction with conventional supportive treatment. The principal complications of such therapy are Graft versus Host Disease and a slow recovery of the recipient's immune system. Concerted research activities in a number of institutions have led to considerable progress in the field of bone marrow transplantation. Improved donor selection, new techniques for stem-cell separation and preservation, as well as effective barrier-nursing and antibiotic decontamination, have made bone marrow transplantation an accepted therapy for marrow depression, including the aplasia caused by excessive exposure to radiation. The review also contains a number of guidelines for the handling of serious radiation accidents. (Auth.)

Pediatric Anaplastic Embryonal Rhabdomyosarcoma: Targeted Therapy Guided by Genetic Analysis and a Patient-Derived Xenograft Study

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Stuart L. Cramer

2018-01-01

Full Text Available Therapy for rhabdomyosarcoma (RMS has generally been limited to combinations of conventional cytotoxic agents similar to regimens originally developed in the late 1960s. Recently, identification of molecular alterations through next-generation sequencing of individual tumor specimens has facilitated the use of more targeted therapeutic approaches for various malignancies. Such targeted therapies have revolutionized treatment for some cancer types. However, malignancies common in children, thus far, have been less amenable to such targeted therapies. This report describes the clinical course of an 8-year-old female with embryonal RMS having anaplastic features. This patient experienced multiple relapses after receiving various established and experimental therapies. Genomic testing of this RMS subtype revealed mutations in BCOR, ARID1A, and SETD2 genes, each of which contributes to epigenetic regulation and interacts with or modifies the activity of histone deacetylases (HDAC. Based on these findings, the patient was treated with the HDAC inhibitor vorinostat as a single agent. The tumor responded transiently followed by subsequent disease progression. We also examined the efficacy of vorinostat in a patient-derived xenograft (PDX model developed using tumor tissue obtained from the patient’s most recent tumor resection. The antitumor activity of vorinostat observed with the PDX model reflected clinical observations in that obvious areas of tumor necrosis were evident following exposure to vorinostat. Histologic sections of tumors harvested from PDX tumor-bearing mice treated with vorinostat demonstrated induction of necrosis by this agent. We propose that the evaluation of clinical efficacy in this type of preclinical model merits further evaluation to determine if PDX models predict tumor sensitivity to specific agents and/or combination therapies.

ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

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Luca Laurenti

2010-08-01

Full Text Available Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%: A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

RENAL ALLOGENEIC TRANSPLANTATION IN PATIENT WITH HAEMOPHILIA B

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N. V. Purlo

2014-01-01

Full Text Available We report the case of successful renal allogeneic transplantation and treatment in a 56-year-old patient with haemophilia B at Hematology Research Center. He has received replacement therapy by factor IX since 2010. The transplant is marked with good renal function during 13 post-transplant months without episodes of rejection or bleeding complications. The complicated surgical interventions are possible in patients with haemophilia В аnd end-stage chronic renal failure in the presence of replacement therapy of IX factor for the purpose of achievement of optimum hemostasis.

Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia

DEFF Research Database (Denmark)

Karlsson, Lene; Forestier, Erik; Hasle, Henrik

2017-01-01

Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children...... relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y ) was 39 ± 4% for the whole group and 43 ± 4......, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS5y was 61 ± 5%. Four of 19 children (21%) survived without...

Comparison of Transplant Waitlist Outcomes for Pediatric Candidates Supported by Ventricular Assist Devices Versus Medical Therapy.

Science.gov (United States)

Law, Sabrina P; Oron, Assaf P; Kemna, Mariska S; Albers, Erin L; McMullan, D Michael; Chen, Jonathan M; Law, Yuk M

2018-05-01

Ventricular assist devices have gained popularity in the management of refractory heart failure in children listed for heart transplantation. Our primary aim was to compare the composite endpoint of all-cause pretransplant mortality and loss of transplant eligibility in children who were treated with a ventricular assist device versus a medically managed cohort. This was a retrospective cohort analysis. Data were obtained from the Scientific Registry of Transplant Recipients. The at-risk population (n = 1,380) was less than 18 years old, either on a ventricular assist device (605 cases) or an equivalent-severity, intensively medically treated group (referred to as MED, 775 cases). None. The impact of ventricular assist devices was estimated via Cox proportional hazards regression (hazard ratio), dichotomizing 1-year outcomes to "poor" (22%: 193 deaths, 114 too sick) versus all others (940 successful transplants, 41 too healthy, 90 censored), while adjusting for conventional risk factors. Among children 0-12 months old, ventricular assist device was associated with a higher risk of poor outcomes (hazard ratio, 2.1; 95% CI, 1.5-3.0; p comparative study of ventricular assist devices versus medical therapy in children. Age is a significant modulator of waitlist outcomes for children with end-stage heart failure supported by ventricular assist device, with the impact of ventricular assist devices being more beneficial in adolescents.

Cell Based Therapies: At Crossroads to find the right Cell source

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Editorial

2012-01-01

Full Text Available Development of newer Cell Based therapies for various diseases and disorders which have limited therapeutic options, is on the rise with clinical trials on cell based therapies being registered all over the world every now and then. However a dilemma arises when it comes to the choosing the ideal source of Stem cells for therapy. Clinical applications of Hematopoietic Stem cells Transplantation (HSCT in the form of Bone Marrow Transplantation has been in practice since the 1950s (1 for malignant and non malignant haematological disorders and even for auto-immune disorders (since 1977 (2, with several reports on successful outcomes after HSCT. The dilemma in HSCT is whether to use allogeneic or autologous sources. While allogeneic sources have the advantage of the graft being devoid of cancer cells, as they are from a healthy donor, they have the risk of life-long Immunosuppression. Autologous Source is advantageous as it needs no immunosuppression but the risk of relapse is high. In adult stem cells, there have been several studies which have demonstrated the various levels of safety and efficacy of both Allogeneic and autologous adult cell sources for application in diseases of the cornea, Spinal Cord, Heart, Liver etc. Each time, a study is published, the patients and the physicians are thrown into a state of perplexity on which source of cell could offer the best possible solution to the various diseases. Next hopping onto Human Embryonic Stem cells, though they were discovered in 1998, the first Human Embryonic Stem cell trial was approved by the FDA in January 2009 but it could hit the road only in October 2010 (3. The trial was for spinal cord injury and a year later, the trial came to a halt in November 2011 when the company, which was financing and pursuing the trial, announced the discontinuation of the trial due to financial reasons (4. However it is worthwhile to note that it was the financial compulsion which led to the

Intraoperative anti-thymocyte globulin-Fresenius (ATG-F) administration as induction immunosuppressive therapy in kidney transplantation.

Science.gov (United States)

Abou-Jaoude, Maroun M; Almawi, Wassim Y

2003-07-01

We reviewed 43 adult kidney transplant patients (32 males and 11 females, 14-68 years of age) performed at our center between July 1999 and February 2002. Donors (39 males and 4 females) comprised two cadaverics, five living-related and 36 living-unrelated; age 18-44 years. Indications for kidney transplantation (KT) were: chronic glomerulonephritis (8), re-transplantation (4) and chronic pyelonephritis (3); kidney disease was unknown in 15 cases. ATG-F was given as a single intra-operative bolus induction therapy in 26 patients; extended ATG-F dose was given in 17 patients because of a high sensitization status, slow graft function (SGF) or development of calcineurin inhibitors toxicity. ATG-F was stopped in seven out of 17 patients because of thrombocytopenia or severe anemia. ATG-F-related fever occurred in six patients. Acute rejection (AR) occurred in eight patients (18%) 5-11 days post-KT. ATG-F was given in three steroid-resistant AR. Infection occurred in 19 patients (44%) for a total of 32 infectious episodes comprising 24 bacterial infections (nine urinary, seven catheter-related and three respiratory), six viral infections (five CMV and one herpes) and two fungal infections (one pulmonary aspergillosis and one catheter-related candidiasis). The hospital stay was 8-75 days for a median of 13 days. The mean serum creatinine upon discharge, at 1 and 6 months after KT were: 2.04+/-0.37, 1.43+/-0.16 and 1.29+/-0.08, respectively. One patient lost his graft on day 9 because of graft microthrombi related to Factor V-Leiden mutation. The 6 months actuarial patient and graft survival were 100 and 97.6%, respectively. ATG-F as a bolus therapy is an effective and safe induction treatment in KT.

Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation.

Science.gov (United States)

Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong

2014-07-16

Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases. Copyright © 2014 the authors 0270-6474/14/349506-10$15.00/0.

Derivation and characterization of monkey embryonic stem cells

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Wolf Don P

2004-06-01

Full Text Available Abstract Embryonic stem (ES cell based therapy carries great potential in the treatment of neurodegenerative diseases. However, before clinical application is realized, the safety, efficacy and feasibility of this therapeutic approach must be established in animal models. The rhesus macaque is physiologically and phylogenetically similar to the human, and therefore, is a clinically relevant animal model for biomedical research, especially that focused on neurodegenerative conditions. Undifferentiated monkey ES cells can be maintained in a pluripotent state for many passages, as characterized by a collective repertoire of markers representing embryonic cell surface molecules, enzymes and transcriptional factors. They can also be differentiated into lineage-specific phenotypes of all three embryonic germ layers by epigenetic protocols. For cell-based therapy, however, the quality of ES cells and their progeny must be ensured during the process of ES cell propagation and differentiation. While only a limited number of primate ES cell lines have been studied, it is likely that substantial inter-line variability exists. This implies that diverse ES cell lines may differ in developmental stages, lineage commitment, karyotypic normalcy, gene expression, or differentiation potential. These variables, inherited genetically and/or induced epigenetically, carry obvious complications to therapeutic applications. Our laboratory has characterized and isolated rhesus monkey ES cell lines from in vitro produced blastocysts. All tested cell lines carry the potential to form pluripotent embryoid bodies and nestin-positive progenitor cells. These ES cell progeny can be differentiated into phenotypes representing the endodermal, mesodermal and ectodermal lineages. This review article describes the derivation of monkey ES cell lines, characterization of the undifferentiated phenotype, and their differentiation into lineage-specific, particularly neural, phenotypes

Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin

International Nuclear Information System (INIS)

Ouji, Yukiteru; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

2006-01-01

We previously showed that Wnt-10b promoted the differentiation of primary skin epithelial cells (MPSEC) toward hair shaft and inner root sheath of the hair follicle (IRS) cells in vitro. In the present study, we found that Wnt-10b promotes the development of hair follicles using a culture of mouse embryonic skin tissue and trichogenesis using a reconstitution experiment with nude mice. Hair follicle development was observed in skin taken from mouse embryos on embryonic day 10.5 following a 2-day culture with recombinant Wnt-10b (rWnt-10b), however, not without rWnt-10b. Brown hair growth was observed at the site of reconstituted skin in Balb/c nude mice where dermal fibroblasts and keratinocytes, derived from C3H/HeN new born mice, were transplanted with Wnt-10b-producing COS cells (Wnt-COS). Without the co-transplantation of Wnt-COS, no hair growth was observed. Our results suggest an important role of Wnt-10b in the initiation of hair follicle development and following trichogenesis

Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis.

Science.gov (United States)

Granito, Alessandro; Bolondi, Luigi

2017-02-01

Underlying liver cirrhosis is present in most patients with hepatocellular carcinoma, and liver transplantation is the only treatment strategy to cure both diseases. All other hepatocellular carcinoma treatment strategies have to take into account residual liver function that concurs with the patient's prognosis and might limit their feasibility. In patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B (CPT-B), owing to borderline liver function, any intervention might be offset by liver function deterioration. In this setting, the decision for hepatocellular carcinoma treatment requires a comprehensive assessment of liver function, not restricted to the CPT classification, in addition to a careful evaluation of the prognostic effect of hepatocellular carcinoma compared with cirrhosis. In this Review, we provide an overview of the literature regarding the benefits and harms of non-transplant therapies in patients with hepatocellular carcinoma and CPT-B cirrhosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

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Tilahun Alelign

2018-01-01

Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

Science.gov (United States)

Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

Islet transplantation: the quest for an ideal source

International Nuclear Information System (INIS)

Younes, Nidal A.; Nothias, J.; Garfinkel, Marc R.

2008-01-01

The progress of islet transplantation as a new therapy for patients with diabetes mellitus depends directly upon the development of efficient and practical immunoisolation methods for the supply of sufficient quantities of islet cells. Without these methods, large scale clinical application of this therapy would be impossible. Two eras of advances can be identified in the development of islet transplantation. The first was an era of experimental animal and human research that centered on islet isolation procedures and transplantation in different species as evidence that transplanted islets have the capability to reverse diabetes. The second was the era of Edmonton protocol, when the focus became the standardization of isolation procedures and introduction of new immunosuppressive drugs to maintain human allograft transplantation. The quest for an alternative source for islets (xenographs, stem cells and cell cultures) to overcome the shortage of human islets was an important issue during these eras. This paper reviews the history of islet transplantation and the current procedures in human allotransplantation, as well as different types of immunoisolation methods. It explores novel approaches to enhancing transplantation site vascularity and islet cell function, whereby future immunoisolation technology could offer additional therapeutic advantages to human islet allotransplantation. (author)

Post-transplant lymphoproliferative disorders.

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Singavi, Arun K; Harrington, Alexandra M; Fenske, Timothy S

2015-01-01

Post-transplant lymphoproliferative disorders (PTLD) are a serious complication after solid organ or allogeneic hematopoietic stem cell transplantation and include a range of diseases from benign proliferations to malignant lymphomas. Risk factors for developing PTLD include Epstein-Barr virus (EBV) infection, recipient age, transplanted organ, type of immunosuppression, and genetics. Uncontrolled proliferation of EBV-infected B cells is implicated in EBV-positive PTLD, whereas the pathogenesis of EBV-negative PTLD may be similar to non-Hodgkin's lymphoma in the general population. The World Health Organization (WHO) classifies PTLD into four categories: early lesions, polymorphic PTLD, monomorphic PTLD, and classical Hodgkin's lymphoma (cHL). Treatment is aimed at cure of PTLD, while maintaining transplanted organ function. However, there are no established guidelines for the treatment of PTLD. Immune suppression reduction (ISR) is the first line of treatment in most cases, with more recent data suggesting early use of rituximab. In more aggressive forms of PTLD, upfront chemotherapy may offer a better and more durable response. Sequential therapy using rituximab followed by chemotherapy has demonstrated promising results and may establish a standard of care. Novel therapies including anti-viral agents, adoptive immunotherapy, and monoclonal antibodies targeting cytokines require further study in the prevention and treatment of PTLD.

Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration

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Kenneth R. Boheler

2011-01-01

Full Text Available Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.

Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population?

Science.gov (United States)

Gorevski, Elizabeth; Succop, Paul; Sachdeva, Jyoti; Cavanaugh, Teresa M; Volek, Paul; Heaton, Pamela; Chisholm-Burns, Marie; Martin-Boone, Jill E

2013-01-01

To measure the association of transplant patients' personality, depression, and quality of life with medication adherence in kidney and liver transplant recipients. A cross-sectional study of liver and kidney transplant recipients greater than 1 year post-transplant was conducted. Patients' adherence with medications was assessed using the Immunosuppressive Therapy Adherence Scale. Personality and depression were assessed using the NEO Five-Factor Inventory Scale and Patient Health Questionnaire 9, respectively. Quality of life was assessed using the Short Form-36, and functional status was determined using the Karnofsky Performance Status Scale. A total of 86 kidney and 50 liver transplant patients completed the surveys. Logistic regression analysis demonstrated an association between depression and adherence with immunosuppressive medications in kidney transplant recipients. Kidney transplant patients who exhibited "low openness" scores were 91% more likely to be nonadherent. Kidney transplant patients' physical functional status was strongly associated with nonadherence, and for each point increase in functionality the patients' adherence increased by 4%. In the liver sample, age was associated with adherence. For every year increase in age, adherence increased by 7%. The presence of low openness as a personality trait, poor physical functional status, and depression were associated with adherence in the kidney transplant population. In the liver transplant population, younger age was associated with nonadherence.

Evolving paradigms for desensitization in managing broadly HLA sensitized transplant candidates.

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Reinsmoen, Nancy L; Lai, Chi-Hung; Vo, Ashley; Jordan, Stanley C

2012-04-01

The broadly human leukocyte antigen (HLA) sensitized patient awaiting organ transplantation remains a persistent and significant problem for transplant medicine. Sensitization occurs as a consequence of exposure to HLA antigens through pregnancy, blood and platelet transfusions, and previous transplants. Early experience with desensitization protocols coupled with improved diagnostics for donor-specific antibodies (DSAs) and renal pathology have greatly improved transplant rates and outcomes for patients once considered un-transplantable or at high risk for poor outcomes. More recent advances have occurred through implementation of a national allocation system requiring the entering of unacceptable antigens that reduces the rate of crossmatch positivity. Current desensitization therapies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells and modifiers of complement-mediated injury. Here we discuss the important advancements in desensitization including defining the risk for antibody-mediated rejection prior to transplantation and the evolution of therapies aimed at reducing the impact of antibody injury on allografts.

Systematic review of induced pluripotent stem cell technology as a potential clinical therapy for spinal cord injury.

Science.gov (United States)

Kramer, Anne S; Harvey, Alan R; Plant, Giles W; Hodgetts, Stuart I

2013-01-01

Transplantation therapies aimed at repairing neurodegenerative and neuropathological conditions of the central nervous system (CNS) have utilized and tested a variety of cell candidates, each with its own unique set of advantages and disadvantages. The use and popularity of each cell type is guided by a number of factors including the nature of the experimental model, neuroprotection capacity, the ability to promote plasticity and guided axonal growth, and the cells' myelination capability. The promise of stem cells, with their reported ability to give rise to neuronal lineages to replace lost endogenous cells and myelin, integrate into host tissue, restore functional connectivity, and provide trophic support to enhance and direct intrinsic regenerative ability, has been seen as a most encouraging step forward. The advent of the induced pluripotent stem cell (iPSC), which represents the ability to "reprogram" somatic cells into a pluripotent state, hails the arrival of a new cell transplantation candidate for potential clinical application in therapies designed to promote repair and/or regeneration of the CNS. Since the initial development of iPSC technology, these cells have been extensively characterized in vitro and in a number of pathological conditions and were originally reported to be equivalent to embryonic stem cells (ESCs). This review highlights emerging evidence that suggests iPSCs are not necessarily indistinguishable from ESCs and may occupy a different "state" of pluripotency with differences in gene expression, methylation patterns, and genomic aberrations, which may reflect incomplete reprogramming and may therefore impact on the regenerative potential of these donor cells in therapies. It also highlights the limitations of current technologies used to generate these cells. Moreover, we provide a systematic review of the state of play with regard to the use of iPSCs in the treatment of neurodegenerative and neuropathological conditions. The

Recovery of behavioral symptoms in hemi-parkinsonian rhesus monkeys through combined gene and stem cell therapy.

Science.gov (United States)

Zhou, Yan; Sun, Maosheng; Li, Hongjun; Yan, Min; He, Zhanlong; Wang, Wenju; Wang, Wanpu; Lu, Shuaiyao

2013-04-01

The use of adipose mesenchymal stromal cells (ASCs) in cellular and genic therapy has attracted considerable attention as a possible treatment for neurodegenerative disorders, including Parkinson disease. However, the effects of gene therapy combined with intracerebral cell transplantation have not been well defined. Recent studies have demonstrated the respective roles of LIM homeobox transcription factor 1, alpha (LMX1A) and Neurturin (NTN) in the commitment of embryonic stem cells (ESCs) to a midbrain dopaminergic neuronal fate and the commitment of mesenchymal stromal cells to cells supporting the nutrition and protection of neurons. We investigated a novel in vitro neuronal differentiation strategy with the use of LMX1A and Neurturin. We were able to elicit a neural phenotype regarding cell morphology, specific gene/protein expression and physiological function. Neuronal-primed ASCs derived from rhesus monkey (rASCs) combined with adenovirus containing NTN and tyrosine hydroxylase (TH) (Ad-NTN-TH) were implanted into the striatum and substantia nigra of methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored with the use of behavioral tests and health measures until the fourth month after implantation. The differentiated cells transcribed and expressed a variety of dopaminergic neuron-specific genes involved in the SHH/LMX1A pathway. Single-photon emission computed tomography analysis and postmortem analysis revealed that the grafting of rASCs combined with Ad-NTN-TH had neuroprotective effects compared with Ad-NTN-TH or rASCs alone. Behavioral measures demonstrated autograft survival and symptom amelioration. These findings may lead to cellular sources for autologous transplantation of Parkinson disease. Combined transplantation of Ad-NTN-TH and induced rASCs expressing LMX1A and NTN may be a better therapy candidate for the treatment of Parkinson disease. Copyright © 2013 International Society

β-Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells.

Science.gov (United States)

Sui, Lina; Danzl, Nichole; Campbell, Sean R; Viola, Ryan; Williams, Damian; Xing, Yuan; Wang, Yong; Phillips, Neil; Poffenberger, Greg; Johannesson, Bjarki; Oberholzer, Jose; Powers, Alvin C; Leibel, Rudolph L; Chen, Xiaojuan; Sykes, Megan; Egli, Dieter

2018-01-01

β-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into β-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature β-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These β-cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-β-cells maintain normal blood glucose levels after ablation of the mouse endogenous β-cells. Cystic structures, but no teratomas, were observed in NT-ES-β-cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in β-cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in induced pluripotent stem cell lines. These results demonstrate the suitability of NT-ES-β-cells for cell replacement for type 1 diabetes and provide proof of principle for therapeutic cloning combined with cell therapy. © 2017 by the American Diabetes Association.

Effect of developmental stage of HSC and recipient on transplant outcomes

Science.gov (United States)

Arora, Natasha; Wenzel, Pamela L.; McKinney-Freeman, Shannon L.; Ross, Samantha J.; Kim, Peter G.; Chou, Stephanie S.; Yoshimoto, Momoko; Yoder, Mervin C.; Daley, George Q.

2014-01-01

Summary The first hematopoietic stem cells (HSCs) that engraft irradiated adult mice arise in the aortagonad-mesonephros (AGM) on embryonic day 11.5 (E11.5). However, at this stage there is a discrepancy between the apparent frequency of HSCs suggested by imaging and their rarity when measured by limiting dilution transplant. We have attempted to reconcile this difference using neonatal recipients, which are more permissive for embryonic HSC engraftment. We found that embryonic HSCs from E9.5 and E10.5 preferentially engrafted neonates, whereas developmentally mature, definitive HSCs from E14.5 fetal liver (FL) or adult bone marrow (BM) more robustly engrafted adults. Neonatal engraftment was enhanced after treating adult BM-derived HSCs with interferon. Adult BM-derived HSCs preferentially homed to the liver in neonatal mice yet showed balanced homing to the liver and spleen in adults. These findings emphasize the functional differences between nascent and mature definitive HSCs. PMID:24914562

Prevalence and correlates of medication non-adherence among kidney transplant recipients more than 6 months post-transplant: a cross-sectional study

OpenAIRE

Weng, Francis L; Chandwani, Sheenu; Kurtyka, Karen M; Zacker, Christopher; Chisholm-Burns, Marie A; Demissie, Kitaw

2013-01-01

Background Among kidney transplant recipients, non-adherence with immunosuppressive medications frequently precedes allograft loss. We sought to determine the prevalence and correlates of medication non-adherence among kidney transplant recipients. Methods We performed a single-center, cross-sectional study of kidney transplant recipients who were at least 6 months post-transplant. We measured self-reported adherence using the Immunosuppressive Therapy Adherence Scale (ITAS, which is scored f...

Pediatric renal transplantation in a highly sensitised child-8 years on.

LENUS (Irish Health Repository)

Quinlan, Catherine

2012-01-26

Highly sensitised children have markedly reduced chances of receiving a successful deceased donor renal transplant, increased risk of rejection, and decreased graft survival. There is limited experience with the long-term followup of children who have undergone desensitization. Following 2 failed transplants, our patient was highly sensitised. She had some immunological response to intravenous immunoglobulin (IVIg) but this was not sustained. We developed a protocol involving sequential therapies with rituximab, IVIg, and plasma exchange. Immunosuppressant therapy at transplantation consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. At the time of transplantation, historical crossmatch was ignored. Current CDC crossmatch was negative, but T and B cell flow crossmatch was positive, due to donor-specific HLA Class I antibodies. Further plasma exchange and immunoglobulin therapy were given pre- and postoperatively. Our patient received a deceased donor-kidney-bearing HLA antigens to which she originally had antibodies, which would have precluded transplant. The graft kidney continues to function well 8 years posttransplant.

Pediatric Renal Transplantation in a Highly Sensitised Child—8 Years On

Directory of Open Access Journals (Sweden)

Catherine Quinlan

2011-01-01

Full Text Available Highly sensitised children have markedly reduced chances of receiving a successful deceased donor renal transplant, increased risk of rejection, and decreased graft survival. There is limited experience with the long-term followup of children who have undergone desensitization. Following 2 failed transplants, our patient was highly sensitised. She had some immunological response to intravenous immunoglobulin (IVIg but this was not sustained. We developed a protocol involving sequential therapies with rituximab, IVIg, and plasma exchange. Immunosuppressant therapy at transplantation consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. At the time of transplantation, historical crossmatch was ignored. Current CDC crossmatch was negative, but T and B cell flow crossmatch was positive, due to donor-specific HLA Class I antibodies. Further plasma exchange and immunoglobulin therapy were given pre- and postoperatively. Our patient received a deceased donor-kidney-bearing HLA antigens to which she originally had antibodies, which would have precluded transplant. The graft kidney continues to function well 8 years posttransplant.

Parvovirus-B19-associated complications in renal transplant recipients.

Science.gov (United States)

Waldman, Meryl; Kopp, Jeffrey B

2007-10-01

Parvovirus B19 is a common human pathogen, causing erythema infectiosum in children, hydrops fetalis in pregnant women, and transient aplastic crisis in patients with chronic hemolytic anemia. Immunosuppressed patients can fail to mount an effective immune response to B19, resulting in prolonged or persistent viremia. Renal transplant recipients can develop symptomatic B19 infections as a result of primary infection acquired via the usual respiratory route or via the transplanted organ, or because of reactivation of latent or persistent viral infection. The most common manifestations of B19 infection in immunosuppressed patients are pure red cell aplasia and other cytopenias. Thus, this diagnosis should be considered in transplant recipients with unexplained anemia and reticulocytopenia or pancytopenia. Collapsing glomerulopathy and thrombotic microangiopathy have been reported in association with B19 infection in renal transplant recipients, but a causal relationship has not been definitively established. Prompt diagnosis of B19 infection in the renal transplant recipient requires a high index of suspicion and careful selection of diagnostic tests, which include serologies and polymerase chain reaction. Most patients benefit from intravenous immunoglobulin therapy and/or alteration or reduction of immunosuppressive therapy. Conservative therapy might be sufficient in some cases.

Allogeneic Stem Cell Transplantation: A Historical and Scientific Overview.

Science.gov (United States)

Singh, Anurag K; McGuirk, Joseph P

2016-11-15

The field of hematopoietic stem cell transplant (HSCT) has made ground-breaking progress in the treatment of many malignant and nonmalignant conditions. It has also pioneered the concepts of stem cell therapy and immunotherapy as a tool against cancer. The success of transplant for hematologic malignancies derives both from the ability to treat patients with intensive chemoradiotherapy and from potent graft-versus-leukemia (GVL) effects mediated by donor immunity. Additionally, HSCT has been a curative therapy for several nonmalignant hematologic disorders through the provision of donor-derived hematopoiesis and immunity. Preclinical and clinical research in the field has contributed to an advanced understanding of histocompatibility, graft-versus-host disease (GVHD), GVL effect, and immune reconstitution after transplant. Improved donor selection, tailored conditioning regimens, and better supportive care have helped reduce transplant-related morbidity and mortality and expanded access. The development of unrelated donor registries and increased utilization of cord blood and partially matched related donor transplants have ensured a donor for essentially everyone who needs a transplant. However, significant barriers still remain in the form of disease relapse, GVHD infectious complications, and regimen-related toxicities. Recent developments in the field of cellular therapy are expected to further improve the efficacy of transplant. In this review, we discuss the current science of HSCT from a historical perspective, highlighting major discoveries. We also speculate on future directions in this field. Cancer Res; 76(22); 6445-51. ©2016 AACR. ©2016 American Association for Cancer Research.

Post-transplantation Infections in Bolivia.

Science.gov (United States)

Arze, S; Arze, L; Abecia, C

2016-03-01

Over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. Fifteen were urinary tract infections, recurrent in 4 patients. There were 8 cytomegalovirus infections, three of them fatal when intravenous (IV) ganciclovir was not available. Seven patients had a reactivation of tuberculosis (TB) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-TB therapy. Three patients transplanted before routine prophylaxis with the use of acyclovir developed an extensive herpes zoster infection in the 1st 6 months after transplantation, which was resolved with the use of oral acyclovir, and 1 had a disseminated herpes simplex infection resolved with the use of IV acyclovir. Three patients transplanted before routine prophylaxis with trimethoprim sulfa developed Pneumocystis carinii pneumonia in the 1st 6 months after transplantation, which was fatal in one of them. In 2 patients, we found a Nocardia infection, confined to the lung, which was cured in one of the cases and systemic and fatal in the other. Two patients transplanted before routine prophylaxis with the use of nystatin developed esophageal candidiasis in the 1st 6 months after transplantation. One patient developed infective endocarditis in a stenotic bicuspid aortic valve and died 10 years later after another incident of infective endocarditis at the prosthetic aortic valve. Two patients developed an extensive condyloma at the penis, perianal region, and perineum owing to human papillomavirus, requiring extensive surgical resection and podophyllin applications. Another patient developed fatal post-transplantation lymphoproliferative disease due to Epstein-Barr virus infection 15 years after transplantation. One patient developed a severe and fatal mucocutaneous leishmaniasis with no response to conventional antimonial therapy. It is interesting to note that despite Chagas disease being endemic

Current concepts on cytomegalovirus infection after liver transplantation.

Science.gov (United States)

Lee, Sang-Oh; Razonable, Raymund R

2010-09-27

Cytomegalovirus (CMV) is the most common viral pathogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted allograft. In addition, CMV has been significantly associated with an increased predisposition to allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, one should also reduce the degree of immunosuppression. In one recent controlled clinical trial, valganciclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ (including liver) transplant recipients. In this article, the authors review the

Haematopoietic stem cell transplantation: activities (2014 report) in a ...

African Journals Online (AJOL)

PROMOTING ACCESS TO AFRICAN RESEARCH ... Introduction: Hematopoietic Stem Cell transplantation (HSCT) is the only curative therapy for ... Activities: The stem cell transplant centre at the University of Benin Teaching Hospital Edo ...

Transplant tourism: Outcomes of United States residents who undergo kidney transplantation overseas.

Science.gov (United States)

Canales, Muna T; Kasiske, Bertram L; Rosenberg, Mark E

2006-12-27

Although international commerce in kidney transplantation is a reality, little is known about U.S. residents who travel abroad for kidney transplantation. We retrospectively reviewed the clinical outcomes of patients who were evaluated at the University of Minnesota Medical Center or Hennepin County Medical Center, but then surreptitiously underwent kidney transplantation overseas. We identified 10 patients who underwent kidney transplantation outside the United States between September 16, 2002 and June 30, 2006 and then returned for care in our programs. Eight were transplanted in Pakistan (all Somali), one was transplanted in China (Chinese), and one was transplanted in Iran (Iranian). All but one had a living donor. Mean age was 36.8+/-12.5 years with median follow-up of 2.0 years (range 0.4-3.7). Three patients communicated their intent to travel abroad before transplantation. Induction immunosuppressive therapy (if any) was available in 3/10, and initial maintenance immunosuppression was known in 5/10. Complications were primarily infectious, with six potentially life-threatening infections in four patients. At last follow-up, mean serum creatinine was 1.13+/-0.34 mg/dL, acute rejection occurred in 2/10, 1/10 grafts failed due to acute rejection, and 9/10 patients were alive. Kidney function and graft survival were generally good after surreptitious overseas kidney transplantation. Major problems included incomplete perioperative information communicated to the posttransplant care facility and a high incidence of posttransplant infections. Longer follow-up and detailed cost analysis are needed to better understand the implications of the growing phenomenon of transplant tourism.

Clinical experience with thymoglobulin and antithymocyte globulin-Fresenius as induction therapy in renal transplant patients: a retrospective study.

Science.gov (United States)

Cicora, Federico; Mos, Fernando; Paz, Marta; Roberti, Javier

2013-10-01

We describe our experiences with, and compare the outcomes of, 2 groups of renal transplant patients treated with thymoglobulin or antithymocyte globulin-Fresenius as induction therapy at transplant to reduce the incidence of acute rejection and prevent delayed allograft function. Twenty-four recipients of deceased-donor or living-donor kidney transplants received thymoglobulin, and 23 patients received antithymocyte globulin-Fresenius. Patient and graft survival and efficacy and safety were assessed at 3 months. The demographic characteristics of both groups were comparable, but the predominant donor type was significantly different. Incidence of complications, delayed graft function, and creatinine concentrations were comparable in both groups. At 3 months after the transplant, patient survival rate was 92% in the thymoglobulin group and 96% in the antithymocyte globulin-Fresenius group (P > .05), and death-censored graft survival rate for both groups was not significantly different. Average hematocrit and lymphocyte, neutrophil, and platelet counts were comparable in both groups at 3 months' follow-up. Average white blood count at 1 month was significantly different between the groups: at 5.62 ± 2.45 × 103 cells/mm³ in the thymoglobulin group and 7.85 ± 4.10 × 103 cells/mm³ in the ATG-F group (P Fresenius were generally comparable.

Cellular models and therapies for age-related macular degeneration

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David L. Forest

2015-05-01

Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

Transplantation of hematopoietic and lymphoid cells in mice

International Nuclear Information System (INIS)

Bortin, M.M.; Rimm, A.A.; Rose, W.C.; Truitt, R.L.; Saltzstein, E.C.

1976-01-01

CBA mice were exposed to a supralethal dose of whole body x-irradiation and received transplants of graded, small doses of bone marrow, fetal liver, or fetal liver plus fetal thymus cells obtained from H-2 matched C58 or H-2 mismatched A donors. Survival at 20 days was used to evaluate the ability of the transplants to restore hematopoiesis following the acute radiation injury. In the higher dose ranges of 6 x 10 7 and 1.2 x 10 8 cells/kg body weight, the fetal cells were as effective as adult bone marrow in both the matched and mismatched strain combinations. Survival at 100 days was used to evaluate the severity of chronic graft-versus-host disease produced by each of the transplants. In the higher dose ranges, cells from fetal donors promoted higher long-term survival rates than did comparable doses of bone marrow cells in both the matched and mismatched strain combinations. The most important finding was that cells from mismatched unrelated fetal donors (using a cell dose per kilogram body weight comparable to the number of fetal liver and thymus cells which would be obtainable from one human fetus at 14 weeks of embryonation) promoted higher long-term survival rates than did bone marrow transplants from matched unrelated donors

Reversal of acute (''malignant'') myelosclerosis by allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Wolf, J.L.; Spruce, W.E.; Bearman, R.M.; Forman, S.J.; Scott, E.P.; Fahey, J. L.; Farbstein, M.J.; Rappaport, H.; Blume, K.G.

1982-01-01

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor

Imaging in haematopoietic stem cell transplantation

International Nuclear Information System (INIS)

Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J.

2003-01-01

Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants

Imaging in haematopoietic stem cell transplantation

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Evans, A.; Steward, C.G.; Lyburn, I.D.; Grier, D.J

2003-03-01

Haematopoietic stem cell transplantation (SCT) is used to treat a wide range of malignant and non-malignant haematological conditions, solid malignancies, and metabolic and autoimmune diseases. Although imaging has a limited role before SCT, it is important after transplantation when it may support the clinical diagnosis of a variety of complications. It may also be used to monitor the effect of therapy and to detect recurrence of the underlying disease if the transplant is unsuccessful. We present a pictorial review of the imaging of patients who have undergone SCT, based upon 15 years experience in a large unit performing both adult and paediatric transplants.

Hematopoietic stem cell transplantation for chronic lymphocytic leukemia.

Science.gov (United States)

Gladstone, Douglas E; Fuchs, Ephraim

2012-03-01

Although hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many aggressive hematologic malignancies, the role of HSCT in chronic lymphocytic leukemia (CLL) has remained controversial. Now in the era of improved conventional treatment and better prognostication of long-term outcome, a review of autologous and allogeneic HSCT in CLL treatment is warranted. Despite an improved disease-free survival in some patients, multiple, prospective, randomized autologous HSCT CLL trials fail to demonstrate an overall survival benefit as compared to conventional therapy. Allogeneic bone marrow transplantation, although limited by donor availability, can successfully eradicate CLL with adverse prognostic features. In the older CLL patients, nonmyeloablative allogeneic transplants are better tolerated than myeloablative transplants. Nonmyeloablative allogeneic transplants are less effective in heavily diseased burdened patients. Outside of a clinical protocol, autologous HSCT for CLL cannot be justified. Nonmyeloablative allogeneic transplantation should be considered in high-risk populations early in the disease process, when disease burden is most easily controlled. Alternative donor selection using haploidentical donors and posttransplantation cyclophosphamide has the potential to vastly increase the availability of curative therapy in CLL while retaining a low treatment-related toxicity.

Generic tacrolimus in solid organ transplantation

DEFF Research Database (Denmark)

Taube, D; Jones, G; O'Beirne, J

2014-01-01

The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which...... innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other...

Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties

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Hua Jin

2015-01-01

Full Text Available The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as embryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C 6 root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C 6 brachial plexus injury site (1 × 10 6 cells/mL, 3 μL/injection, 25 injections immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C 6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also significantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effectively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals.

An injectable spheroid system with genetic modification for cell transplantation therapy.

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Uchida, Satoshi; Itaka, Keiji; Nomoto, Takahiro; Endo, Taisuke; Matsumoto, Yu; Ishii, Takehiko; Kataoka, Kazunori

2014-03-01

The new methodology to increase a therapeutic potential of cell transplantation was developed here by the use of three-dimensional spheroids of transplanting cells subsequent to the genetic modification with non-viral DNA vectors, polyplex nanomicelles. Particularly, spheroids in regulated size of 100-μm of primary hepatocytes transfected with luciferase gene were formed on the micropatterned culture plates coated with thermosensitive polymer, and were recovered in the form of injectable liquid suspension simply by cooling the plates. After subcutaneously transplanting these hepatocyte spheroids, efficient transgene expression was observed in host tissue for more than a month, whereas transplantation of a single-cell suspension from a monolayer culture resulted in an only transient expression. The spheroid system contributed to the preservation of innate functions of transplanted hepatocytes in the host tissue, such as albumin expression, thereby possessing high potential for expressing transgene. Intravital observation of transplanted cells showed that those from spheroid cultures had a tendency to localize in the vicinity of blood vessels, making a favorable microenvironment for preserving cell functionality. Furthermore, spheroids transfected with erythropoietin-expressing DNA showed a significantly higher hematopoietic effect than that of cell suspensions from monolayer cultures, demonstrating high potential of this genetically-modified spheroid transplantation system for therapeutic applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation.

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Aridon, Paolo; Ragonese, Paolo; Di Benedetto, Norma; Grasso, Giovanni; Conaldi, Pier Giulio; D'Amelio, Marco; Savettieri, Giovanni

2009-12-01

Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.

Small bowel preservation for intestinal transplantation : a review

NARCIS (Netherlands)

Roskott, Anne Margot C.; Nieuwenhuijs, Vincent B.; Dijkstra, Gerard; Koudstaal, Lyan G.; Leuvenink, Henri G. D.; Ploeg, Rutger J.

P>Intestinal transplantation has become the therapy of choice for patients with intestinal failure and life-threatening complications from total parenteral nutrition. Results, however, remain inferior as compared with other transplant types with the quality of the organ graft as the most important

Clearance of hepatitis C virus after living-donor liver transplantation in spite of residual viremia on end date of interferon therapy before transplantation

Science.gov (United States)

Ichikawa, Tatsuki; Nakao, Kazuhiko; Hamasaki, Keisuke; Honda, Takuya; Shibata, Hidetaka; Akahoshi, Mana; Eguchi, Susumu; Takatsuki, Mitsuhisa; Kanematsu, Takashi; Eguchi, Katsumi

2007-01-01

Interferon (IFN) therapy is the only treatment strategy for hepatitis C virus (HCV) infection after liver transplantation (LT), but prophylactic and treatable IFN therapy after LT has been shown to be insufficient due to the adverse effects of IFN and rivabirin. In this paper, we describe the disappearance of HCV after LT without IFN therapy in the presence of residual viremia on the day of LT. We herein report our findings since this is considered an important case for the anti-HCV strategy of post LT. A 60-year old woman with LC and HCC was referred to Nagasaki University Hospital in August 2004. After she underwent LT on February 18, 2005, we injected peg-IFN-α-2a the 11th time at 18 wk and HCV-RNA was still positive in the serum at LT. The serum HCV-RNA was negative one month after operation and subsequently dissolved 15 mo after operation without IFN therapy. As a result, we speculate that if HCV-RNA is positive while HCV core antigen is negative before LT, then it may lead to clearance of HCV after LT. Therefore long acting peg-IFN-α-2a is thus considered a potentially effective agent for the treatment of HCV-related cirrhosis before LT. PMID:17696240

Long-term effects of islet transplantation.

Science.gov (United States)

Holmes-Walker, D Jane; Kay, Thomas W H

2016-10-01

Islet transplantation has made great progress in recent years. This is a remarkable technical feat but raises the question of what the long-term benefits and risks are for type I diabetes recipients. Graft survival continues to improve, and recent multicenter studies show that islet transplantation is particularly effective to prevent hypoglycemic events even in those who do not become insulin-independent and to achieve excellent glycemic control. Concerns include histocompatability leucocyte antigen (HLA) sensitization and other risks including from immunosuppression that islet transplantation shares with other forms of allotransplantation. Reversal of hypoglycemia unawareness and protection from severe hypoglycemia events are two of the main benefits of islet transplantation and they persist for the duration of graft function. Islet transplantation compares favorably with other therapies for those with hypoglycemia unawareness, although new technologies have not been tested head-to-head with transplantation. HLA sensitization increases with time after transplantation especially if immunosuppression is ceased and is a risk for those who may require future transplantation as well as being associated with loss of graft function.

Knowledge-based immunosuppressive therapy for kidney transplant patients--from theoretical model to clinical integration.

Science.gov (United States)

Seeling, Walter; Plischke, Max; de Bruin, Jeroen S; Schuh, Christian

2015-01-01

Immunosuppressive therapy is a risky necessity after a patient received a kidney transplant. To reduce risks, a knowledge-based system was developed that determines the right dosage of the immunosuppresive agent Tacrolimus. A theoretical model, to classify medication blood levels as well as medication adaptions, was created using data from almost 500 patients, and over 13.000 examinations. This model was then translated into an Arden Syntax knowledge base, and integrated directly into the hospital information system of the Vienna General Hospital. In this paper we give an overview of the construction and integration of such a system.

Viral Infection in Renal Transplant Recipients

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Jovana Cukuranovic

2012-01-01

Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

Nonadherence to immunosuppressive therapy in kidney transplant recipients: can technology help?

Science.gov (United States)

Nerini, Erika; Bruno, Fulvio; Citterio, Franco; Schena, Francesco P

2016-10-01

End-stage kidney disease is a life-threatening condition that compels patients to accept either dialysis or transplant. Kidney transplantation is the best choice for patients with end-stage kidney disease because it ensures higher quality of life and longer survival rates than other choices, with less cost for the healthcare system. However, in order for renal recipients to maintain the functioning graft they must take lifelong immunosuppressive medications, with possible side effects and low medication adherence. It is known that low medication adherence in kidney transplant recipients may cause poor outcomes, chronic graft rejection, and graft failure. In this review, the authors give an overview of nonadherence in the transplant setting. In addition, they analyze the role of different technologies as an aid to improve adherence, with a focus on mobile-phone based solutions to monitor and enhance kidney transplant recipient compliance.

Materializing Heart Regeneration: Biomimicry of Key Observations in Cell Transplantation Therapies and Natural Cardiac Regeneration

Science.gov (United States)

Kong, Yen P.; Jongpaiboonkit, Leena

2016-07-01

New regenerative paradigms are needed to address the growing global problem of heart failure as existing interventions are unsatisfactory. Outcomes from the current paradigm of cell transplantation have not been stellar but the mechanistic knowledge learned from them is instructive in the development of future paradigms. An emerging biomaterial-based approach incorporating key mechanisms and additional ones scrutinized from the process of natural heart regeneration in zebrafish may become the next evolution in cardiac repair. We highlight, with examples, tested key concepts and pivotal ones that may be integrated into a successful therapy.

Therapy for Cerebral Palsy by Human Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Combined With Basic Rehabilitation Treatment

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Che Zhang MD

2015-03-01

Full Text Available Background. Cerebral palsy (CP is the most common cause leading to childhood disability. Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs transplantation is a promising alternative considering the safety and efficacy in current reports. This report represents a case of hUCB-MSCs transplantation combined with basic rehabilitation treatment beginning as early as age 6 months with follow-up as long as 5 years. Methods. A 6-year-old female patient was diagnosed with CP at age 6 months. The patient accepted 4 infusions of intravenous hUCB-MSCs in each course and received 4 courses of transplantation totally. A series of assessments were performed before the first transplantation, including laboratory tests, CDCC Infant Mental Development Scale, and Gross Motor Function Measure-88 (GMFM-88. Then annual assessments using the GMFM-88, Ashworth spasm assessment, and comprehensive function assessment scale were made in addition to the annual laboratory tests. In addition, electroencephalography and brain magnetic resonance imaging were conducted before transplantation and in the follow-up phase. Rehabilitation and safety follow-up have been ongoing for 5 years up to date. Results. There was no complaint about adverse effects during hospitalization or postoperative follow-up. Motor function recovered to normal level according to the evaluation of scales. Language function improved significantly. Linguistic rehabilitation therapy was enhanced for further improvement. Conclusions. The clinical application of hUC-MSCs combined with basic rehabilitation treatment was effective and safe for improving motor and comprehensive function in a patient with CP.

Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.

Science.gov (United States)

Cassileth, Barrie R; Vickers, Andrew J; Magill, Lucanne A

2003-12-15

High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT. Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States. Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls. Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT. Copyright 2003 American Cancer Society.

Association of elevated pretransplant sCD30 levels with graft loss in 206 patients treated with modern immunosuppressive therapies after renal transplantation.

Science.gov (United States)

Heinemann, Falko M; Rebmann, Vera; Witzke, Oliver; Philipp, Thomas; Broelsch, Christoph E; Grosse-Wilde, Hans

2007-03-27

Recent reports suggest that high pretransplant serum levels of soluble CD30 (sCD30) are a risk factor for rejections after kidney transplantation. The aim of our study was to elucidate the predictive value of pretransplant sCD30 levels for kidney transplantation outcome in a single-center patient cohort that has been treated with modern immunosuppressive therapies after transplantation. We retrospectively analyzed sCD30 in multiple pretransplant sera from 206 patients, of whom 174 were transplanted with a cadaveric kidney and 32 patients received an allograft from a living donor. Renal function after transplantation was estimated by measuring serum creatinine and by rejection diagnosis. We could demonstrate a statistically significant association between increased pretransplant sCD30 values and graft failures (P=0.005). Receiver operating curve analysis revealed a cutoff value of 124 U/mL pretransplant sCD30. A multivariate analysis confirmed pretransplant sCD30 values >124 U/mL (P=0.011) and rejection episodes (PsCD30 levels and the incidence of graft failure, but we could not confirm that the development of rejection episodes is correlated with pretransplant sCD30 values.

Surgical therapy by sandwich transplantation using a dermal collagen-elastin matrix and full thickness split grafts and gait rehabilitation with individualized orthesis

Directory of Open Access Journals (Sweden)

Uwe Wollina

2012-01-01

Full Text Available Painful callosities of the feet (PCOF are a rare complaint in children with severe impairment of mobility and quality of life. There is no medical treatment available.We investigated the usefulness of a recently developed combined transplant technique-the sandwich transplantation with dermal collagen-elastin template in this rare condition. A 14-year-old boy suffered from PCOF for several years without any improvement by topical therapy, dermabrasion, and oral retinoids. He was unable to walk normally and suffered from severe pain. We performed a complete deep excision of the hyperkeratotic plantar tissue in general anaesthesia in combination with sandwich transplantation in the same setting. Dry sheets of collagen-elastin matrix (1 mm thickness were placed on the soft tissue defects and covered by full-thickness mesh graft transplants from the upper leg. An individualized orthosis was produced for gait rehabilitation. Two weeks after surgery the gait-related pain was reduced remarkably. Using the orthosis, the boy was able to walk pain-free even on staircase. Surgery of PCOF with sandwich transplantation and gait rehabilitation appears to be a promising strategy for this rare condition.

Artificial organs and transplantation.

Science.gov (United States)

Splendiani, G; Cipriani, S; Vega, A; Casciani, C U

2003-05-01

Nowadays artificial devices are not able to totally and undefinitely replace the loss of function of all vital organs and artificial organs can be used only to bridge the time to transplantation, which must be considered the first choice in the therapeutical approach for many chronic diseases. Since general population aging process is leading to an increase of organ demand, the gap between performed and requested transplantation is hard to fill. Xenotransplantation is nowadays only an experimental alternative solution and we have to do our best using available artificial organs to increase and improve the survival of patients waiting for transplantation. In this meeting we particularly dealt about organ function replacing therapy, especially regarding the kidney, heart, liver, pancreas and ear.

Pituitary cell differentiation from stem cells and other cells: toward restorative therapy for hypopituitarism?

Science.gov (United States)

Willems, Christophe; Vankelecom, Hugo

2014-01-01

The pituitary gland, key regulator of our endocrine system, produces multiple hormones that steer essential physiological processes. Hence, deficient pituitary function (hypopituitarism) leads to severe disorders. Hypopituitarism can be caused by defective embryonic development, or by damage through tumor growth/resection and traumatic brain injury. Lifelong hormone replacement is needed but associated with significant side effects. It would be more desirable to restore pituitary tissue and function. Recently, we showed that the adult (mouse) pituitary holds regenerative capacity in which local stem cells are involved. Repair of deficient pituitary may therefore be achieved by activating these resident stem cells. Alternatively, pituitary dysfunction may be mended by cell (replacement) therapy. The hormonal cells to be transplanted could be obtained by (trans-)differentiating various kinds of stem cells or other cells. Here, we summarize the studies on pituitary cell regeneration and on (trans-)differentiation toward hormonal cells, and speculate on restorative therapies for pituitary deficiency.

Imaging of complications from hematopoietic stem cell transplant

International Nuclear Information System (INIS)

Pandey, Tarun; Maximin, Suresh; Bhargava, Puneet

2014-01-01

Stem cell transplant has been the focus of clinical research for a long time given its potential to treat several incurable diseases like hematological malignancies, diabetes mellitus, and neuro-degenerative disorders like Parkinson disease. Hematopoietic stem cell transplantation (HSCT) is the oldest and most widely used technique of stem cell transplant. HSCT has not only been used to treat hematological disorders including hematological malignancies, but has also been found useful in treamtent of genetic, immunological, and solid tumors like neuroblastoma, lymphoma, and germ cell tumors. In spite of the rapid advances in stem cell technology, success rate with this technique has not been universal and many complications have also been seen with this form of therapy. The key to a successful HSCT therapy lies in early diagnosis and effective management of complications associated with this treatment. Our article aims to review the role of imaging in diagnosis and management of stem cell transplant complications associated with HSCT

Transplantation of human neonatal foreskin stromal cells in ex vivo organotypic cultures of embryonic chick femurs

DEFF Research Database (Denmark)

Aldahmash, Abdullah; Vishnubalaji, Radhakrishnan

2017-01-01

NSSCs in ex vivo organotypic cultures of embryonic chick femurs. Isolated embryonic chick femurs (E10 and E11) were cultured for 10 days together with micro-mass cell pellets of hNSSCs, human umbilical vein endothelial cells (HUVEC) or a combination of the two cell types. Changes in femurs gross morphology......We have previously reported that human neonatal foreskin stromal cells (hNSSCs) promote angiogenesis in vitro and in chick embryo chorioallantoic membrane (CAM) assay in vivo. To examine the in vivo relevance of this observation, we examined in the present study the differentiation potential of h......NSSC + HUVEC cultures. Our data suggest that organotypic cultures can be employed to test the differentiation potential of stem cells and demonstrate the importance of stem cell interaction with 3D-intact tissue microenvironment for their differentiation....

Transplantation of olfactory ensheathing cells as adjunct cell therapy for peripheral nerve injury.

Science.gov (United States)

Radtke, Christine; Wewetzer, Konstantin; Reimers, Kerstin; Vogt, Peter M

2011-01-01

Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush and nerve disruption defects. Transplantation of myelin-forming cells, such as Schwann cells (SCs) or olfactory ensheathing cells (OECs), may be beneficial to the regenerative process because the applied cells could mediate neurotrophic and neuroprotective effects by secretion of chemokines. Moreover, myelin-forming cells are capable of bridging the repair site by establishing an environment permissive to axonal regeneration. The cell types that are subject to intense investigation include SCs and OECs either derived from the olfactory bulb or the olfactory mucosa, stromal cells from bone marrow (mesenchymal stem cells, MSCs), and adipose tissue-derived cells. OECs reside in the peripheral and central nervous system and have been suggested to display unique regenerative properties. However, so far OECs were mainly used in experimental studies to foster central regeneration and it was not until recently that their regeneration-promoting activity for the peripheral nervous system was recognized. In the present review, we summarize recent experimental evidence regarding the regenerative effects of OECs applied to the peripheral nervous system that may be relevant to design novel autologous cell transplantation therapies. © 2011 Cognizant Comm. Corp.

[Melanoma in organ transplant patients].

Science.gov (United States)

Lévêque, L; Dalac, S; Dompmartin, A; Louvet, S; Euvrard, S; Catteau, B; Hazan, M; Schollhamer, M; Aubin, F; Dreno, B; Daguin, P; Chevrant-Breton, J; Frances, C; Bismuth, M J; Tanter, Y; Lambert, D

2000-02-01

The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean

Management of Minerals and Bone Disorders after Kidney Transplantation

Science.gov (United States)

Kalantar-Zadeh, Kamyar; Molnar, Miklos Z; Kovesdy, Csaba P.; Mucsi, Istvan; Bunnapradist, Suphamai

2012-01-01

Purpose of review Mineral and bone disorders (MBD), inherent complications of moderate and advanced chronic kidney disease (CKD), occur frequently in kidney transplant recipients. However, much confusion exists about clinical application of diagnostic tools and preventive or treatment strategies to correct bone loss or mineral disarrays in transplanted patients. We have reviewed the recent evidence about prevalence and consequences of MBD in kidney transplant recipients and examined diagnostic, preventive and therapeutic options to this end. Recent findings Low turnover bone disease occurs more frequently after kidney transplantation according to bone biopsy studies. The risk of fracture is high, especially in the first several months after kidney transplantation. Alterations in minerals (calcium, phosphorus and magnesium) and biomarkers of bone metabolism (PTH, alkaline phosphatase, vitamin D and FGF-23) are observed with varying impact on post-transplant outcomes. Calcineurin inhibitors are linked to osteoporosis, whereas steroid therapy may lead to both osteoporosis and varying degrees of osteonecrosis. Sirolimus and everolimus might have a bearing on osteoblasts proliferation and differentiation or decreasing osteoclast mediated bone resorption. Selected pharmacologic interventions for treatment of MBD in transplant patients include steroid withdrawal, the use of bisphosphonates, vitamin D derivatives, calcimimetics, teriparatide, calcitonin and denosumab. Summary MBD following kidney transplantation is common and characterized by loss of bone volume and mineralization abnormalities often leading to low turnover bone disease. Although there are no well-established therapeutic approaches for management of MBD in renal transplant recipients, clinicians should continue individualizing therapy as needed. PMID:22614626

[Ethical aspects of human embryonic stem cell use and commercial umbilical cord blood stem cell banking. Ethical reflections on the occasion of the regulation of the European Council and Parliament on advanced therapy medicinal products].

Science.gov (United States)

Virt, G

2010-01-01

The regulation of the European Council and Parliament on advanced therapy medicinal products also includes therapies with human embryonic stem cells. The use of these stem cells is controversially and heavily discussed. Contrary to the use of adult stem cells, medical and ethical problems concerning the use of human embryonic stem cells persists, because this use is based on the destruction of human life at the very beginning. The regulation foresees, therefore, subsidiarity within the European Member States. Although there are no ethical problems in principle with the use of stem cells from the umbilical cord blood, there are social ethical doubts with the banking of these stem cells for autologous use without any currently foreseeable medical advantage by commercial blood banks. Also in this case subsidiarity is valid.

Allorecognition pathways in transplant rejection and tolerance.

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Ali, Jason M; Bolton, Eleanor M; Bradley, J Andrew; Pettigrew, Gavin J

2013-10-27

With the advent of cellular therapies, it has become clear that the success of future therapies in prolonging allograft survival will require an intimate understanding of the allorecognition pathways and effector mechanisms that are responsible for chronic rejection and late graft loss.Here, we consider current understanding of T-cell allorecognition pathways and discuss the most likely mechanisms by which these pathways collaborate with other effector mechanisms to cause allograft rejection. We also consider how this knowledge may inform development of future strategies to prevent allograft rejection.Although both direct and indirect pathway CD4 T cells appear active immediately after transplantation, it has emerged that indirect pathway CD4 T cells are likely to be the dominant alloreactive T-cell population late after transplantation. Their ability to provide help for generating long-lived alloantibody is likely one of the main mechanisms responsible for the progression of allograft vasculopathy and chronic rejection.Recent work has suggested that regulatory T cells may be an effective cellular therapy in transplantation. Given the above, adoptive therapy with CD4 regulatory T cells with indirect allospecificity is a rational first choice in attempting to attenuate the development and progression of chronic rejection; those with additional properties that enable inhibition of germinal center alloantibody responses hold particular appeal.

The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells

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Naoaki Sakata

2018-05-01

Full Text Available This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells.

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Sakata, Naoaki; Yoshimatsu, Gumpei; Kodama, Shohta

2018-05-07

This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

A case of toxic epidermal necrolysis initially affecting the skin site of radiation therapy for an intra-cranial post-transplantation lymphoma

International Nuclear Information System (INIS)

Tanoue, Toshihide; Egawa, Kiyofumi; Fukushima, Satoshi; Wakasugi, Syoji; Ono, Tomomichi; Yoshida, Shinsuke; Kouchi, Masato; Nishi, Kazuhiko

2006-01-01

We report a case of post-transplantation lymphoma (intra-cranial EBV-related malignant lymphoma) who developed toxic epidermal necrolysis (TEN) during concomitant phenobarbital administration and radiotherapy. The erythema exsudativum multiforme-like eruption first appeared on the site of radiation and extended to approximately 35% of the body surface. After stopping radiation therapy and all medications, including immunosuppressant, anticonvulsant, and diuretic drugs, treatment was successfully administered by systemic corticosteroids including semi-pulse therapy (500 mg of methylpredonisolone sodium succinate for 3 days). (author)

ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

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Patrizia Chiusolo

2010-05-01

Full Text Available

Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.

Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%:

A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity.

The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.

Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

Allogeneic Hematopoietic Stem Cell Transplantation Is an Effective Salvage Therapy for Patients with Chronic Myeloid Leukemia Presenting with Advanced Disease or Failing Treatment with Tyrosine Kinase Inhibitors.

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Nair, Anish P; Barnett, Michael J; Broady, Raewyn C; Hogge, Donna E; Song, Kevin W; Toze, Cynthia L; Nantel, Stephen H; Power, Maryse M; Sutherland, Heather J; Nevill, Thomas J; Abou Mourad, Yasser; Narayanan, Sujaatha; Gerrie, Alina S; Forrest, Donna L

2015-08-01

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for chronic myeloid leukemia (CML); however, it is rarely utilized given the excellent long-term results with tyrosine kinase inhibitor (TKI) treatment. The purpose of this study is to examine HSCT outcomes for patients with CML who failed TKI therapy or presented in advanced phase and to identify predictors of survival, relapse, and nonrelapse mortality (NRM). Fifty-one patients with CML underwent HSCT for advanced disease at diagnosis (n = 15), TKI resistance as defined by the European LeukemiaNet guidelines (n = 30), TKI intolerance (n = 2), or physician preference (n = 4). At a median follow-up of 71.9 months, the 8-year overall survival (OS), event-free survival (EFS), relapse, and NRM were 68%, 46%, 41%, and 23%, respectively. In univariate analysis, predictors of OS included first chronic phase (CP1) disease status at HSCT (P = .0005), European Society for Blood and Marrow Transplantation score 1 to 4 (P = .04), and complete molecular response (CMR) to HSCT (P treatment to optimize transplantation outcomes. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Successful repigmentation of vitiligo after allogeneic bone marrow transplantation for Hodgkin′s lymphoma by autologous noncultured melanocyte-keratinocyte transplantation

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Huijuan Tang

2015-01-01

Full Text Available The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin′s lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation.

Chronic digitalis therapy in patients before heart transplantation is an independent risk factor for increased posttransplant mortality

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Rivinius R

2017-10-01

Full Text Available Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Ann-Kathrin Rahm,1,3 Fabrice F Darche,1 Dierk Thomas,1 Tom Bruckner,4 Philipp Ehlermann,1 Hugo A Katus,1 Andreas O Doesch1,5 1Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Heidelberg, 2Department of Cardiac Surgery, Heidelberg University Hospital, Heidelberg, 3Faculty of Medicine, University of Heidelberg, Heidelberg, 4Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, 5Asklepios Klinik Bad Salzungen GmbH, Department of Pneumology and Oncology, Bad Salzungen, Germany Objectives: Digitalis therapy (digoxin or digitoxin in patients with heart failure is subject to an ongoing debate. Recent data suggest an increased mortality in patients receiving digitalis. This study investigated the effects of chronic digitalis therapy prior to heart transplantation (HTX on posttransplant outcomes.Patients and methods: This was a retrospective, observational, single-center study. It comprised 530 adult patients who were heart-transplanted at Heidelberg University Hospital between 1989 and 2012. Patients with digitalis prior to HTX (≥3 months were compared to those without (no or <3 months of digitalis. Patients with digitalis were further subdivided into patients receiving digoxin or digitoxin. Primary outcomes were early posttransplant atrial fibrillation and mortality.Results: A total of 347 patients (65.5% had digitalis before HTX. Of these, 180 received digoxin (51.9% and 167 received digitoxin (48.1%. Patients with digitalis before HTX had a significantly lower 30-day (P=0.0148 and 2-year (P=0.0473 survival. There was no significant difference between digoxin and digitoxin in 30-day (P=0.9466 or 2-year (P=0.0723 survival. Multivariate analysis for posttransplant 30-day mortality showed pretransplant digitalis therapy as an independent risk factor (hazard ratio =2.097, CI: 1.036–4.248, P=0.0397. Regarding atrial

Face time: educating face transplant candidates.

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Lamparello, Brooke M; Bueno, Ericka M; Diaz-Siso, Jesus Rodrigo; Sisk, Geoffroy C; Pomahac, Bohdan

2013-01-01

Face transplantation is the innovative application of microsurgery and immunology to restore appearance and function to those with severe facial disfigurements. Our group aims to establish a multidisciplinary education program that can facilitate informed consent and build a strong knowledge base in patients to enhance adherence to medication regimes, recovery, and quality of life. We analyzed handbooks from our institution's solid organ transplant programs to identify topics applicable to face transplant patients. The team identified unique features of face transplantation that warrant comprehensive patient education. We created a 181-page handbook to provide subjects interested in pursuing transplantation with a written source of information on the process and team members and to address concerns they may have. While the handbook covers a wide range of topics, it is easy to understand and visually appealing. Face transplantation has many unique aspects that must be relayed to the patients pursuing this novel therapy. Since candidates lack third-party support groups and programs, the transplant team must provide an extensive educational component to enhance this complex process. As face transplantation continues to develop, programs must create sound education programs that address patients' needs and concerns to facilitate optimal care.

Transplantation Dose Alters the Differentiation Program of Hematopoietic Stem Cells.

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Brewer, Casey; Chu, Elizabeth; Chin, Mike; Lu, Rong

2016-05-24

Hematopoietic stem cell (HSC) transplantation is the most prevalent stem cell therapy, but it remains a risky procedure. To improve this treatment, it is important to understand how transplanted stem cells rebuild the blood and immune systems and how this process is impacted by transplantation variables such as the HSC dose. Here, we find that, in the long term following transplantation, 70%-80% of donor-HSC-derived clones do not produce all measured blood cell types. High HSC doses lead to more clones that exhibit balanced lymphocyte production, whereas low doses produce more T-cell-specialized clones. High HSC doses also produce significantly higher proportions of early-differentiating clones compared to low doses. These complex differentiation behaviors uncover the clonal-level regeneration dynamics of hematopoietic regeneration and suggest that transplantation dose can be exploited to improve stem cell therapy. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Nutritional status of renal transplant patients | du Plessis | South ...

African Journals Online (AJOL)

... 0.0001) during the post-transplant period. Conclusions. Several nutritional abnormalities were observed, which primarily reflect the side-effects of immunosuppressive therapy. The causes, consequences and treatment of the vitamin B6 and vitamin C deficiencies in renal transplant recipients need further investigation.

Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation

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Yamano, Noriko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Kimura, Tohru, E-mail: tkimura@patho.med.osaka-u.ac.jp [Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Watanabe-Kushima, Shoko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Shinohara, Takashi [Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501 (Japan); Nakano, Toru, E-mail: tnakano@patho.med.osaka-u.ac.jp [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

2010-02-12

Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation. We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes. Sphere cell transfer to the original feeder-free ESC cultures resulted in chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was observed. These results indicate that Akt signaling promotes a novel metastable and pluripotent state that is intermediate to those of ESCs and PGCs.

Dyslipidaemia among renal transplant recipients: cyclosporine versus tacrolimus.

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Fazal, Muhammad Asim; Idrees, Muhammad Khalid; Akhtar, Syed Fazal

2014-05-01

To compare new onset dyslipidaemia in live-related renal transplant recipients taking cyclosporine versus tacrolimus after 3 months of therapy. The randomised controlled trial was conducted at the Sindh Institute of Urology and Transplantation (SIUT) Karachi, from September 2010 to April 2011, and included 182 End Stage Renal Disease patients on maintenance haemodialysis with pre-transplant normal lipid profile. The patients, who had live-related renal transplant, were randomly allocated to two equal groups using lottery. Group A received cyclosporine (3 mg/kg) and group B was treated with tacrolimus (0.1 mg/kg). All patients had pre-transplant fasting lipid profile checked when they were on maintenance haemodialysis and 3 months after renal transplantation. Serum fasting lipid profile was collected by taking 5 ml blood by venipuncture after an overnight fast of 9-12 hours. SPSS 10 was used for statistical analyses. Of the 182 patients, 144 (79.1%) were males and 38 (20.9%) were females. The overall mean age was 30.18 +/- 9.57 years, and the mean weight was 54.41 +/- 11.144 kg. Significant difference was not observed between the two groups regarding age and weight of the patients. Dyslipidaemia was found in 115(63.2%) subjects; 61(67%) in group A and 54 (59.3%) in group B. There was no statistical difference (p=0.28) when comparison was done after 3 months of therapy. The occurrence of new onset hyperlipidaemia is similar in renal transplant recipients receiving either cyclosporine or tacrolimus in first 3 months post-transplant, but there is room for more research in this field as dyslipidaemia following successful renal transplantation is a frequent and persistent complication.

Late-onset persistent retinal microvascular changes after bone marrow transplantation: 3-year follow-up

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Muccioli Cristina

2002-01-01

Full Text Available Purpose: To describe a case of persistent retinopathy after bone marrow transplantation in the absence of radiation therapy. Methods: Case Report. Results: A 42 year-old man developed bilateral visual loss 15 months after receiving a bone marrow transplant for acute leukemia. The patient was treated with a high dose of cyclosporin A and oral corticosteroids. No radiation therapy was given. Late-onset, multiple, bilateral cotton-wool spots developed 15 months after the bone marrow transplantation and still persist. After three years other cotton-wool spots arose in the absence of any immunosuppressive therapy. Conclusions: Bone marrow transplantation microvasculopathy of the retina may be related to certain combinations of chemotherapy drugs or immunosuppression itself and may persist in the absence of these immunosuppressive drugs.

Other women's wombs: uterus transplants and gestational surrogacy

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Robertson, John A.

2016-01-01

The birth of a child after uterus transplant from a living donor in Sweden in October, 2013 has spurred reproductive and transplant physicians in Europe and North America to investigate whether uterus transplants, from living or cadaveric donors, will be a safe and effective therapy for women with uterine insufficiency. While progress with uterus transplant depends on medical factors, there are also important ethical and legal concerns. Uterus transplant is essential for women without access to surrogacy. It may also be sought by infertile women who dislike surrogacy. This article examines medical, ethical, legal, and policy issues that arise with womb transplant, including the role of surrogacy policies that make them necessary. The conclusion is that there is a clear ethical path for either surrogacy or uterus transplant to be used by women with uterine insufficiency. PMID:27774233

Other women's wombs: uterus transplants and gestational surrogacy.

Science.gov (United States)

Robertson, John A

2016-04-01

The birth of a child after uterus transplant from a living donor in Sweden in October, 2013 has spurred reproductive and transplant physicians in Europe and North America to investigate whether uterus transplants, from living or cadaveric donors, will be a safe and effective therapy for women with uterine insufficiency. While progress with uterus transplant depends on medical factors, there are also important ethical and legal concerns. Uterus transplant is essential for women without access to surrogacy. It may also be sought by infertile women who dislike surrogacy. This article examines medical, ethical, legal, and policy issues that arise with womb transplant, including the role of surrogacy policies that make them necessary. The conclusion is that there is a clear ethical path for either surrogacy or uterus transplant to be used by women with uterine insufficiency.

Desordem linfoproliferativa pós-transplante em paciente pediátrico Post-transplantation lymphoproliferative disorder in pediatric patient

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Paulo Manuel Pêgo Fernandes

2006-10-01

Full Text Available Terapias de imunossupressão, a que pacientes transplantados devem ser submetidos, os expõe a um alto risco de desenvolver desordens linfoproliferativas pós-transplante (PTLD. Descrevemos o caso de uma criança submetida a transplante cardíaco aos sete meses de idade e que acabou desenvolvendo PTLD, aos nove anos, diagnosticada por meio de retirada de nódulo pulmonar.Immunosuppressive therapy for transplanted patients exposes them to a high risk of developing posttransplantation lymphoproliferative disorders (PTLD. We report the case of a child undergoing heart transplantation at seven months of age who developed PTLD at nine years of age, diagnosed by resection of a pulmonary nodule.

Is there an association between immunosuppressant therapy medication adherence and depression, quality of life, and personality traits in the kidney and liver transplant population?

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Gorevski E

2013-04-01

Full Text Available Elizabeth Gorevski,1 Paul Succop,1 Jyoti Sachdeva,1 Teresa M Cavanaugh,1 Paul Volek,1 Pamela Heaton,1 Marie Chisholm-Burns,2 Jill E Martin-Boone1 1University of Cincinnati, Cincinnati, OH, USA, 2University of Tennessee College of Pharmacy, Memphis, TN, USA Objectives: To measure the association of transplant patients' personality, depression, and quality of life with medication adherence in kidney and liver transplant recipients. Methods: A cross-sectional study of liver and kidney transplant recipients greater than 1 year post-transplant was conducted. Patients’ adherence with medications was assessed using the Immunosuppressive Therapy Adherence Scale. Personality and depression were assessed using the NEO Five-Factor Inventory Scale and Patient Health Questionnaire 9, respectively. Quality of life was assessed using the Short Form-36, and functional status was determined using the Karnofsky Performance Status Scale. Results: A total of 86 kidney and 50 liver transplant patients completed the surveys. Logistic regression analysis demonstrated an association between depression and adherence with immunosuppressive medications in kidney transplant recipients. Kidney transplant patients who exhibited “low openness” scores were 91% more likely to be nonadherent. Kidney transplant patients’ physical functional status was strongly associated with nonadherence, and for each point increase in functionality the patients adherence increased by 4%. In the liver sample, age was associated with adherence. For every year increase in age, adherence increased by 7%. Conclusion: The presence of low openness as a personality trait, poor physical functional status, and depression were associated with adherence in the kidney transplant population. In the liver transplant population, younger age was associated with nonadherence. Keywords: adherence, transplant, liver, kidney

Lung Transplantation for Lymphangioleiomyomatosis in Japan

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Ando, Katsutoshi; Okada, Yoshinori; Akiba, Miki; Kondo, Takashi; Kawamura, Tomohiro; Okumura, Meinoshin; Chen, Fengshi; Date, Hiroshi; Shiraishi, Takeshi; Iwasaki, Akinori; Yamasaki, Naoya; Nagayasu, Takeshi; Chida, Masayuki; Inoue, Yoshikazu; Hirai, Toyohiro; Seyama, Kuniaki; Mishima, Michiaki

2016-01-01

Background Lung transplantation has been established as the definitive treatment option for patients with advanced lymphangioleiomyomatosis (LAM). However, the prognosis after registration and the circumstances of lung transplantation with sirolimus therapy have never been reported. Methods In this national survey, we analyzed data from 98 LAM patients registered for lung transplantation in the Japan Organ Transplantation Network. Results Transplantation was performed in 57 patients as of March 2014. Survival rate was 86.7% at 1 year, 82.5% at 3 years, 73.7% at 5 years, and 73.7% at 10 years. Of the 98 patients, 21 had an inactive status and received sirolimus more frequently than those with an active history (67% vs. 5%, p<0.001). Nine of twelve patients who remained inactive as of March 2014 initiated sirolimus before or while on a waiting list, and remained on sirolimus thereafter. Although the statistical analysis showed no statistically significant difference, the survival rate after registration tended to be better for lung transplant recipients than for those who awaited transplantation (p = 0.053). Conclusions Lung transplantation is a satisfactory therapeutic option for advanced LAM, but the circumstances for pre-transplantation LAM patients are likely to alter with the use of sirolimus. PMID:26771878

Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation

International Nuclear Information System (INIS)

Zou, Ying; Zhang, Ningzhe; Ellerby, Lisa M.; Davalos, Albert R.; Zeng, Xianmin; Campisi, Judith; Desprez, Pierre-Yves

2012-01-01

Highlights: ► hESCs and their progeny, NSCs and neurons, were exposed to ionizing radiation. ► Upon irradiation, most hESCs died within 5–7 h. ► Surviving NSCs underwent senescence and displayed features of astrocytes. ► Surviving NSCs did not display the secretory phenotype expressed by pure astrocytes. ► This study is to better understand the stress-responses of hESCs and their progeny. -- Abstract: Human embryonic stem cells (hESCs) hold promise for the treatment of many human pathologies. For example, hESCs and the neuronal stem cells (NSCs) and neurons derived from them have significant potential as transplantation therapies for a variety of neurodegenerative diseases. Two concerns about the use of hESCs and their differentiated derivatives are their ability to function and their ability to resist neoplastic transformation in response to stresses that inevitably arise during their preparation for transplantation. To begin to understand how these cells handle genotoxic stress, we examined the responses of hESCs and derived NSCs and neurons to ionizing radiation (IR). Undifferentiated hESCs were extremely sensitive to IR, with nearly all the cells undergoing cell death within 5–7 h. NSCs and neurons were substantially more resistant to IR, with neurons showing the most resistant. Of interest, NSCs that survived IR underwent cellular senescence and acquired astrocytic characteristics. Unlike IR-treated astrocytes, however, the NSC-derived astrocytic cells that survived IR did not display the typical pro-inflammatory, pro-carcinogenic senescence-associated secretory phenotype. These findings suggest distinct genotoxic stress-responses of hESCs and derived NSC and neuronal populations, and suggest that damaged NSCs, while failing to function, may not cause local inflammation.

Responses of human embryonic stem cells and their differentiated progeny to ionizing radiation

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Zou, Ying; Zhang, Ningzhe; Ellerby, Lisa M.; Davalos, Albert R.; Zeng, Xianmin; Campisi, Judith [Buck Institute for Research on Aging, Novato, CA 94945 (United States); Desprez, Pierre-Yves, E-mail: pydesprez@cpmcri.org [Buck Institute for Research on Aging, Novato, CA 94945 (United States); California Pacific Medical Center, Research Institute, San Francisco, CA 94107 (United States)

2012-09-14

Highlights: Black-Right-Pointing-Pointer hESCs and their progeny, NSCs and neurons, were exposed to ionizing radiation. Black-Right-Pointing-Pointer Upon irradiation, most hESCs died within 5-7 h. Black-Right-Pointing-Pointer Surviving NSCs underwent senescence and displayed features of astrocytes. Black-Right-Pointing-Pointer Surviving NSCs did not display the secretory phenotype expressed by pure astrocytes. Black-Right-Pointing-Pointer This study is to better understand the stress-responses of hESCs and their progeny. -- Abstract: Human embryonic stem cells (hESCs) hold promise for the treatment of many human pathologies. For example, hESCs and the neuronal stem cells (NSCs) and neurons derived from them have significant potential as transplantation therapies for a variety of neurodegenerative diseases. Two concerns about the use of hESCs and their differentiated derivatives are their ability to function and their ability to resist neoplastic transformation in response to stresses that inevitably arise during their preparation for transplantation. To begin to understand how these cells handle genotoxic stress, we examined the responses of hESCs and derived NSCs and neurons to ionizing radiation (IR). Undifferentiated hESCs were extremely sensitive to IR, with nearly all the cells undergoing cell death within 5-7 h. NSCs and neurons were substantially more resistant to IR, with neurons showing the most resistant. Of interest, NSCs that survived IR underwent cellular senescence and acquired astrocytic characteristics. Unlike IR-treated astrocytes, however, the NSC-derived astrocytic cells that survived IR did not display the typical pro-inflammatory, pro-carcinogenic senescence-associated secretory phenotype. These findings suggest distinct genotoxic stress-responses of hESCs and derived NSC and neuronal populations, and suggest that damaged NSCs, while failing to function, may not cause local inflammation.

Imaging in lung transplants: Checklist for the radiologist

International Nuclear Information System (INIS)

Madan, Rachna; Chansakul, Thanissara; Goldberg, Hilary J

2014-01-01

Post lung transplant complications can have overlapping clinical and imaging features, and hence, the time point at which they occur is a key distinguisher. Complications of lung transplantation may occur along a continuum in the immediate or longer postoperative period, including surgical and mechanical problems due to size mismatch and vascular as well as airway anastomotic complication, injuries from ischemia and reperfusion, acute and chronic rejection, pulmonary infections, and post-transplantation lymphoproliferative disorder. Life expectancy after lung transplantation has been limited primarily by chronic rejection and infection. Multiple detector computed tomography (MDCT) is critical for evaluation and early diagnosis of complications to enable selection of effective therapy and decrease morbidity and mortality among lung transplant recipients

High-dose therapy and autologous bone marrow transplantation for Hodgkin's disease patients with relapses potentially treatable by radical radiation therapy

International Nuclear Information System (INIS)

Pezner, Richard D.; Nademanee, Auayporn; Forman, Stephen J.

1995-01-01

Purpose: A retrospective review evaluated the results of autologous bone marrow transplantation (A-BMT) for patients with relapsed Hodgkin's disease (HD) who were potentially treatable by radical radiation therapy (RRT). Methods and Materials: Evaluated patient cases met the following criteria: initial treatment with chemotherapy (with or without involved field radiation therapy 20 Gy to spinal cord); HD at time of salvage therapy limited to lymph nodes, Waldeyer's ring, liver, spleen, direct extension sites, and/or one lung. Results: There were 23 A-BMT patients treated between 1986 and 1991 who fulfilled the criteria. Three (13%) patients died from treatment-related complications and eight (35%) developed nonfatal Grade 3-4 complications. The 3-year actuarial disease-free survival rate was 61%. The 3-year disease-free survival rate was 55% for the nine patients with at least one prior disease-free interval (DFI) > 12 months, 67% for nine patients with DFI 0.10). These results are comparable to retrospective studies of RRT results in selected relapsed HD patients. Conclusions: Long-term disease-free survival is frequently possible with either A-BMT or RRT appropriately selected relapsed HD patients. In considering treatment options, important prognostic factors include initial stage of disease, number of prior relapses, DFI, and extent of relapsed disease

Stem cell therapy for diabetes

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K O Lee

2012-01-01

Full Text Available Stem cell therapy holds immense promise for the treatment of patients with diabetes mellitus. Research on the ability of human embryonic stem cells to differentiate into islet cells has defined the developmental stages and transcription factors involved in this process. However, the clinical applications of human embryonic stem cells are limited by ethical concerns, as well as the potential for teratoma formation. As a consequence, alternative forms of stem cell therapies, such as induced pluripotent stem cells, umbilical cord stem cells and bone marrow-derived mesenchymal stem cells, have become an area of intense study. Recent advances in stem cell therapy may turn this into a realistic treatment for diabetes in the near future.

The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation.

Science.gov (United States)

Lichtenberg, Shelly; Rahamimov, Ruth; Green, Hefziba; Fox, Benjamin D; Mor, Eytan; Gafter, Uzi; Chagnac, Avry; Rozen-Zvi, Benaya

2017-07-01

Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

Science.gov (United States)

Zhang, Shufang; Jiang, Yang Zi; Zhang, Wei; Chen, Longkun; Tong, Tong; Liu, Wanlu; Mu, Qin; Liu, Hua; Ji, Junfeng; Ouyang, Hong Wei

2013-01-01

Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models. PMID:22788986

Cytokines and T lymphocytes in transplantation : targets for immunotherapy

NARCIS (Netherlands)

A.C.Th.M. Vossen (Ann)

1995-01-01

textabstractOrgan transplantation has become an established therapy in patients suffering from diseases leading to organ failure. Table I shows the number of organ transplants performed in the Eurotransplant area from 1 g90 to 1993. The use of potent immunosuppressive drugs and effective protocols

Autologous Stem Cell Transplant for AL Amyloidosis

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Vivek Roy

2012-01-01

Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

Perspectives on stem cell therapy for cardiac regeneration. Advances and challenges.

Science.gov (United States)

Choi, Sung Hyun; Jung, Seok Yun; Kwon, Sang-Mo; Baek, Sang Hong

2012-01-01

Ischemic heart disease (IHD) accelerates cardiomyocyte loss, but the developing stem cell research could be useful for regenerating a variety of tissue cells, including cardiomyocytes. Diverse sources of stem cells for IHD have been reported, including embryonic stem cells, induced pluripotent stem cells, skeletal myoblasts, bone marrow-derived stem cells, mesenchymal stem cells, and cardiac stem cells. However, stem cells have unique advantages and disadvantages for cardiac tissue regeneration, which are important considerations in determining the specific cells for improving cell survival and long-term engraftment after transplantation. Additionally, the dosage and administration method of stem cells need to be standardized to increase stability and efficacy for clinical applications. Accordingly, this review presents a summary of the stem cell therapies that have been studied for cardiac regeneration thus far, and discusses the direction of future cardiac regeneration research for stem cells.

Management of mineral and bone disorder after kidney transplantation.

Science.gov (United States)

Kalantar-Zadeh, Kamyar; Molnar, Miklos Z; Kovesdy, Csaba P; Mucsi, Istvan; Bunnapradist, Suphamai

2012-07-01

Mineral and bone disorders (MBDs), inherent complications of moderate and advanced chronic kidney disease, occur frequently in kidney transplant recipients. However, much confusion exists about the clinical application of diagnostic tools and preventive or treatment strategies to correct bone loss or mineral disarrays in transplanted patients. We have reviewed the recent evidence about prevalence and consequences of MBD in kidney transplant recipients and examined diagnostic, preventive and therapeutic options to this end. Low turnover bone disease occurs more frequently after kidney transplantation according to bone biopsy studies. The risk of fracture is high, especially in the first several months after kidney transplantation. Alterations in minerals (calcium, phosphorus and magnesium) and biomarkers of bone metabolism (parathyroid hormone, alkaline phosphatase, vitamin D and FGF-23) are observed with varying impact on posttransplant outcomes. Calcineurin inhibitors are linked to osteoporosis, whereas steroid therapy may lead to both osteoporosis and varying degrees of osteonecrosis. Sirolimus and everolimus might have a bearing on osteoblast proliferation and differentiation or decreasing osteoclast-mediated bone resorption. Selected pharmacologic interventions for the treatment of MBD in transplant patients include steroid withdrawal, and the use of bisphosphonates, vitamin D derivatives, calcimimetics, teriparatide, calcitonin and denosumab. MBD following kidney transplantation is common and characterized by loss of bone volume and mineralization abnormalities, often leading to low turnover bone disease. Although there are no well established therapeutic approaches for management of MBD in renal transplant recipients, clinicians should continue individualizing therapy as needed.

Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm

DEFF Research Database (Denmark)

Rasmussen, Camilla Holzmann; Petersen, Dorthe Roenn; Møller, Jonas Bech

2015-01-01

Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin...... and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation....... embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed...

Inflammatory Response in Islet Transplantation

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Mazhar A. Kanak

2014-01-01

Full Text Available Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation.

Inflammatory Response in Islet Transplantation

Science.gov (United States)

Kanak, Mazhar A.; Kunnathodi, Faisal; Lawrence, Michael C.; Levy, Marlon F.

2014-01-01

Islet cell transplantation is a promising beta cell replacement therapy for patients with brittle type 1 diabetes as well as refractory chronic pancreatitis. Despite the vast advancements made in this field, challenges still remain in achieving high frequency and long-term successful transplant outcomes. Here we review recent advances in understanding the role of inflammation in islet transplantation and development of strategies to prevent damage to islets from inflammation. The inflammatory response associated with islets has been recognized as the primary cause of early damage to islets and graft loss after transplantation. Details on cell signaling pathways in islets triggered by cytokines and harmful inflammatory events during pancreas procurement, pancreas preservation, islet isolation, and islet infusion are presented. Robust control of pre- and peritransplant islet inflammation could improve posttransplant islet survival and in turn enhance the benefits of islet cell transplantation for patients who are insulin dependent. We discuss several potent anti-inflammatory strategies that show promise for improving islet engraftment. Further understanding of molecular mechanisms involved in the inflammatory response will provide the basis for developing potent therapeutic strategies for enhancing the quality and success of islet transplantation. PMID:24883060

SINGLE-CENTER EXPERIENCE OF ABO-INCOMPATIBLE LIVER TRANSPLANTATION

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S. V. Gautier

2011-01-01

Full Text Available Since 2008 up to 2010 eight ABO-incompatible liver transplantations have been performed in our center: one of them was urgent liver transplantation to adult patient from deceased donor, other seven were transplantations of left lateral segment to children from living relative donors. Own experience, as well as world one, proves, that barrier of ABO-incompatibility can be overcome more successfully in liver transplantation, particularly in pediatric population, that in other solid organs transplantation. Good results can be achieved even with less ag- gressive immunosuppressive therapy. Recipient conditioning before operation can significantly improve results of ABO-incompatible liver transplantation, but as own experience has shown, often there’s no need to hold some special preparation of children, because their anti-ABO antibodies are very low or absent before transplantation and do not increase after it. Thereby ABO-incompatible liver transplantation is reasonable in urgent cases and in pediatric population because of the limited pull of living relative donors for children. 

PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

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Isidro Jarque

2016-07-01

Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

Desensitization: Overcoming the Immunologic Barriers to Transplantation

Science.gov (United States)

Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

2017-01-01

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

The Effect of One Session Low Level Laser Therapy of Extracted Follicular Units on the Outcome of Hair Transplantation.

Science.gov (United States)

Tabaie, Seyed Mehdi; Berenji Ardestani, Hoda; Azizjalali, Mir Hadi

2016-01-01

Photobiostimulation with low level laser (LLL) has been used in medicine for a long time and its effects have been shown in many diseases. Some studies have evaluated the effect of LLL on androgenic alopecia. One of the most important limitations of the use of LLL in the treatment of alopecia is the requirement for multiple sessions, which is hardly accepted by patients. This study was conducted to evaluate the effect of the irradiation of extracted follicular hair units by LLL on the outcome of hair transplantation. We enrolled 10 patients with androgenic alopecia and after screening tests for infections and other diseases, we extracted hair follicular units. The hair units were divided in two groups. One group was irradiated by LLL 20 minutes before transplantation (660 nm, 80 Hz, 100 mW) and the other one was used as control. The containing plates were labeled as A and B and sent to the operation room. The surgeon was unaware of the therapy assigned to the plates and transplanted them randomly on the right or left side of the head. One hundred follicular units on each sides of the scalp were transplanted symmetrically. The follicles on both sides were evaluated at 3 and 6 months of transplantation for hair growth rate by another physician, blinded to the treatment assigned to each side. Ten patient with androgenic alopecia and mean (SD) age of 31.5 (6.6) years (range 25-45 years) completed the study. All patients had 100% hair growth at 3 and 6 months follow-up except one who had hair growth of 20% at three months of transplantation, which changed to 100% at sixth months. There was no significant difference between the groups regarding hair growth (P > 0.8). One session of LLL irradiation has no significant effect on the outcome of transplanted hair follicles. Studies with larger sample size are needed to draw a definite conclusion.

Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

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Xing, Minzhi [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Sakaria, Sonali [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Dhanasekaran, Renumathy [Stanford University School of Medicine, Division of Gastroenterology and Hepatology (United States); Parekh, Samir; Spivey, James [Emory University School of Medicine, Division of Digestive Diseases, Department of Medicine (United States); Knechtle, Stuart J. [Duke University School of Medicine, Division of Transplant Surgery, Department of Surgery (United States); Zhang, Di [University of Pittsburgh, Department of Biostatistics, Graduate School of Public Health (United States); Kim, Hyun S., E-mail: kevin.kim@yale.edu [Yale School of Medicine, Interventional Radiology, Department of Radiology and Biomedical Imaging (United States)

2017-03-15

Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Xing, Minzhi; Sakaria, Sonali; Dhanasekaran, Renumathy; Parekh, Samir; Spivey, James; Knechtle, Stuart J.; Zhang, Di; Kim, Hyun S.

2017-01-01

Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.

Successful pregnancy and delivery after simultaneous islet-kidney transplantation.

Science.gov (United States)

Assalino, Michela; Podetta, Michele; Demuylder-Mischler, Sandrine; Francini, Katyuska; Pernin, Nadine; Randin, Jean-Pierre; Bosco, Domenico; Andres, Axel; Berney, Thierry

2018-04-19

Allogeneic islet of Langerhans transplantation is a recognized beta-cell replacement therapy for patients affected by type 1 diabetes mellitus. Type 1 diabetes mellitus is a condition associated with an increased risk of adverse outcomes for pregnant women and fetuses. We report the case of a 29-year-old woman with type 1 diabetes mellitus, who underwent successful allogeneic islet transplantation with simultaneous kidney transplantation. She achieved durable insulin independence after 2 islet infusions. Pregnancy was desired and planned 2 years after the last islet infusion. Multidisciplinary monitoring of pregnancy was carried out and the immunosuppressive regimen was adapted. Euglycemia was maintained throughout pregnancy without the need for exogenous insulin. After an uneventful pregnancy, she delivered on term an otherwise healthy male child with imperforate anus that was immediately surgically corrected. In conclusion, allogeneic islet transplantation is a suitable treatment for women of childbearing age with complicated type 1 diabetes mellitus, allowing physiologic glycemic control during pregnancy with a low risk of graft loss. This target can be achieved only by a tight multidisciplinary follow-up, including immunosuppressive therapy adaptation and adequate diabetes and obstetrical monitoring. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Renal-sparing strategies in cardiac transplantation

DEFF Research Database (Denmark)

Gustafsson, Finn; Ross, Heather J

2009-01-01

PURPOSE OF REVIEW: Renal dysfunction due to calcineurin inhibitor (CNI) toxicity is a major clinical problem in cardiac transplantation. The aim of the article is to review the efficacy and safety of various renal sparing strategies in cardiac transplantation. RECENT FINDINGS: Small studies have...... reduction in terms of preserving renal function. Patients with longstanding CNI treatment or proteinuria are less likely to respond favourably to a switch from a CNI-based regimen to a proliferation signal inhibitor-based regimen. SUMMARY: Each cardiac transplant recipient with renal dysfunction must...... documented that late initiation of CNI is safe in patients treated with induction therapy at the time of transplantation. Use of mycophenolate is superior when compared with azathioprine to allow for CNI reduction. More substantial reduction in CNI levels is safe and effective with the introduction...

Aspirin resistance as cardiovascular risk after kidney transplantation

Science.gov (United States)

Sandor, Barbara; Varga, Adam; Rabai, Miklos; Toth, Andras; Papp, Judit; Toth, Kalman; Szakaly, Peter

2014-05-01

International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

Factors that determine self-reported immunosuppressant adherence in kidney transplant recipients: a correlational study.

Science.gov (United States)

Weng, Li-Chueh; Yang, Ya-Chen; Huang, Hsiu-Li; Chiang, Yang-Jen; Tsai, Yu-Hsia

2017-01-01

To determine the factors related to immunosuppressant therapy adherence in kidney transplant recipients in Taiwan. Adherence to immunosuppressant treatment is critical after kidney transplantation. Thus, the factors associated with self-reported medication adherence in kidney transplant recipients warrant investigation. The study used a cross-sectional and correlation design. A convenience sample of 145 kidney transplant recipients was included. Structured questionnaires were used to collect data during 2012-2013. Multivariate linear regression was used to examine the factors related to immunosuppressant therapy adherence. Over half of the participants were female (54·5%), mean age was 45·5 years, and mean year after transplant was 7·4. The mean score for medication adherence was 29·73 (possible score range 7-35). The results of the multivariate linear regression analysis showed that gender (male), low income with a high school or college education, years after transplantation and concerns about medication taking were negatively associated with adherence. Medication self-efficacy was positively associated with adherence. Therapy-related factors, partnerships with healthcare professionals and having private healthcare insurance did not significantly relate to immunosuppressant therapy adherence. Kidney transplant recipients demonstrated a high level of adherence. Strategies to enhance patients' self-efficacy and alleviate concerns about medication may promote medication adherence. Male patients, those with a lower income and those with a higher education level, should be a focus of efforts to maintain adherence to the medication regimen. © 2016 John Wiley & Sons Ltd.

Autologous blood cell therapies from pluripotent stem cells

Science.gov (United States)

Lengerke, Claudia; Daley, George Q.

2010-01-01

Summary The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g. without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select for cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells. PMID:19910091

Dyslipidaemia among renal transplant recipients: cyclosporine versus tacrolimus

International Nuclear Information System (INIS)

Fazal, M. A.; Idrees, M. K.; Akhtar, S. F.

2014-01-01

Objectives: To compare new onset dyslipidaemia in live-related renal transplant recipients taking cyclosporine versus tacrolimus after 3 months of therapy. Methods: The randomised controlled trial was conducted at the Sindh Institute of Urology and Transplantation (SIUT) Karachi, from September 2010 to April 2011, and included 182 End Stage Renal Disease patients on maintenance haemodialysis with pre-transplant normal lipid profile. The patients, who had live-related renal transplant, were randomly allocated to two equal groups using lottery. Group A received cyclosporine (3mg/kg) and group B was treated with tacrolimus (0.1mg/kg). All patients had pre-transplant fasting lipid profile checked when they were on maintenance haemodialysis and 3 months after renal transplantation. Serum fasting lipid profile was collected by taking 5ml blood by venipuncture after an overnight fast of 9-12 hours. SPSS 10 was used for statistical analyses. Results: Of the 182 patients, 144(79.1%) were males and 38(20.9%) were females. The overall mean age was 30.18+-9.57 years, and the mean weight was 54.41+- 11.144kg. Significant difference was not observed between the two groups regarding age and weight of the patients. Dyslipidaemia was found in 115(63.2%) subjects; 61(67%) in group A and 54(59.3%) in group B. There was no statistical difference (p=0.28) when comparison was done after 3 months of therapy. Conclusions: The occurrence of new onset hyperlipidaemia is similar in renal transplant recipients receiving either cyclosporine or tacrolimus in first 3 months post-transplant, but there is room for more research in this field as dyslipidaemia following successful renal transplantation is a frequent and persistent complication. (author)

Comparison of demographic data and immunosupression protocol in patients with and without malignancy after kidney transplantation

International Nuclear Information System (INIS)

Abazar Akbarzadehpasha; Farshid Oliaei; Mohammad Reza Asrari; Reza Alizadeh-Navaei

2010-01-01

Long-term immunosuppressive therapy after renal transplantation increases the risk of developing malignancy. The aim of this study was to determine the demographic parameters and immunosupression protocol in kidney transplant recipients with and without malignancy. This case-control study was undertaken on 12 renal transplant recipients with malignancy and 48 without malignancy at The Shahid Beheshti Kidney Transplantation Center in Babol (north of Iran). Data including age, gender, number of anti-rejection therapies and immunosupression regimen were recorded and analyzed with SPSS and Mann-Whitney Fisher's exact t-test. P value 0.05). Males were signi-ficantly more affected with malignancy compared to females (P < 0.05). Our study shows that there was no significant correlation between age at transplantation, duration of immunosupression treatment and number of anti-rejection therapies and occurrence of post-renal transplantation malignancy; however, the prevalence of malignancy was significantly higher in male patients. The most common malignancy seen was Kaposi's sarcoma followed by lymphoma (Author).

THE ISLAMIC ETHICS OF MITOCHONDRIA TRANSPLANTATION

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Anke Iman Bouzenita

2017-12-01

Full Text Available ABSTRACT: Biotechnology has opened a new chapter with the advent of mitochondria transplantation for cell-based therapy. Mitochondrial transplantation was successfully led to birth; however, cytoplasmic transplantation has caused apprehension, since the mixing of human ooplasm from two different maternal sources may generate mitochondrial DNA (mtDNA heteroplasmy in the offspring. Islamic legal verdicts on human cloning and somatic cell transfer have been overweighing explicit as to its prohibition, due to the change of creation, mixing of lineage and other evaluations. Is mitochondria transplantation equivalent to human cloning in that genetic information is proliferated and does it, therefore, take the same legal rule? Are there possible benefits (masalih for medical treatment that may render mitochondria transplantation permissible, or are possible harms (mafasid overweighing? Or is it a completely different procedure, taking a different rule? The paper will investigate into these questions and discuss the dimensions of Islamic ethics on the issue.

Benefits of ambulatory axillary intra-aortic balloon pump for circulatory support as bridge to heart transplant.

Science.gov (United States)

Umakanthan, Ramanan; Hoff, Steven J; Solenkova, Natalia; Wigger, Mark A; Keebler, Mary E; Lenneman, Andrew; Leacche, Marzia; Disalvo, Thomas G; Ooi, Henry; Naftilan, Allen J; Byrne, John G; Ahmad, Rashid M

2012-05-01

Axillary intra-aortic balloon pump therapy has been described as a bridge to transplant. Advantages over femoral intra-aortic balloon pump therapy include reduced incidence of infection and enhanced patient mobility. We identified the patients who would benefit most from this therapy while awaiting heart transplantation. We conducted a single-center, retrospective observational study to evaluate outcomes from axillary intra-aortic balloon pump therapy. These included hemodynamic parameters, duration of support, and success in bridging to transplant. We selected patients on the basis of history of sternotomy, elevated panel-reactive antibody, and small body habitus. Patients were made to ambulate aggressively beginning on postoperative day 1. Between September 2007 and September 2010, 18 patients underwent axillary intra-aortic balloon pump therapy. All patients had the devices placed through the left axillary artery with a Hemashield side graft (Boston Scientific, Natick, Mass). Before axillary placement, patients underwent femoral placement to demonstrate hemodynamic benefit. Duration of support ranged from 5 to 63 days (median = 19 days). There was marked improvement in ambulatory potential and hemodynamic parameters, with minimal blood transfusion requirements. There were no device-related infections. Some 72% of the patients (13/18) were successfully bridged to transplantation. Axillary intra-aortic balloon pump therapy provides excellent support for selected patients as a bridge to transplant. The majority of the patients were successfully bridged to transplant and discharged. Although this therapy has been described in previous studies, this is the largest series to incorporate a regimen of aggressive ambulation with daily measurements of distances walked. Copyright © 2012. Published by Mosby, Inc.

Photodynamic therapy for actinic keratosis in organ transplant patients

DEFF Research Database (Denmark)

Basset-Seguin, N; Baumann Conzett, K; Gerritsen, M J P

2013-01-01

Background The incidence of actinic keratoses (AK) and non-melanoma skin cancer (NMSC) in organ transplant recipients (OTRs) is significantly higher than in immunocompetent patients. Rates of progression and recurrence following treatment are higher too, in part due to the effects of the immunosu......Background The incidence of actinic keratoses (AK) and non-melanoma skin cancer (NMSC) in organ transplant recipients (OTRs) is significantly higher than in immunocompetent patients. Rates of progression and recurrence following treatment are higher too, in part due to the effects...... investigate induced immunosuppression with PDT in healthy volunteers....

Resultados iniciais da oxigenoterapia hiperbárica empacientes em lista de espera para o transplante hepático Preliminary results of hyperbaric oxygen therapy on patients on the waiting list for liver transplantation

Directory of Open Access Journals (Sweden)

Flávio Kreimer

2011-03-01

benefited with hyperbaric oxygen therapy. AIM: To evaluate clinical and laboratorial data regarding liver function in cirrhotic patients selected for liver transplantation, submitted to hyperbaric oxygen therapy. METHOD: A prospective interventional study was designed, wherein 10 patients were randomized amongst cirrhotic patients selected for liver transplantation. The ages ranged from 20 to 65 years, and all patients presented with a MELD score greater than 15. All patients were submitted to nine sessions of hyperbaric oxygen therapy, on alternated days with the duration of 60 minutes per session, with oxygen atmosphere of 100% and a 2,8 ATM pressure. Dependent parameters included were biochemical and hematologic laboratory values, evaluated before and after hyperbaric oxygen therapy sessions, besides clinical parameters, evaluated considering the Child-Turcotte-Pugh and the MELD scores. Statistical analysis was performed with SPSS (Statistcal Package for Social Sciences. RESULTS: Three patients (30% reported decrease in the number and intensity of encephalopathy. There were no cases of spontaneous bacterial peritonitis and gastrointestinal bleeding, and there were no increases on the severity of ascitis. Two patients reported improvement on pruritus, and four improvement on the general status for few weeks following hyperbaric oxygen sessions. CONCLUSION: Hyperbaric oxygen therapy may improve liver function in cirrhosis, and may help to control complications related to liver failure on the preoperative evaluation for liver transplantation.

Exchange donor transplantation: ethical option for living renal transplantation.

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Gürkan, A; Kaçar, S; Varılsuha, C; Tilif, S; Turunç, V; Doǧan, M; Dheir, H; Sahin, S

2011-04-01

Taking in consideration the opinion of our team, which necessitates obligation of a relative relation between donors and recipients (genetic or matrimonial), we performed donor exchanges as an ethical alternative in living donor transplantations. We reviewed the outcomes of our exchange series. Between July 2003 and August 2010 we performed 110 exchange donor transplantations in four hospitals: one four-way, two three-way, and 100 two-way cases. Donors were mostly spouses (n = 71) or mothers (n = 15). The mean age of the donors was 48.8 (range = 23-69) and the recipients 41.4 years (range = 5-66). Two were transplanted preemptively and the others had a mean dialysis duration of 43 months (range = 1-120). Among 110 patients, three compatible pairs joined the group voluntarily; 71, due to ABO incompatibility and 36, due to crossmatch positivity. Induction therapy was used in 92 patients. HLA mismatches (MM) were: one MM in three; two MM in three; three MM in 18, four MM in 36; five MM in 34; and six MM in 18. Among 90 patients tested for panel-reactive antibodies PRA, five showed class I and 10, class II positivity. In 11 patients, B-cell positivity was detected by flow cytometry. Delayed graft function (n = 2), acute rejection (n = 11), BK virus infection (n = 1), and cytomegalovirus infection (n = 3) were seen postoperatively. Three (2.7%) patients died due to sepsis. Five patients returned to dialysis program due to interstitial fibrosis tubular atrophy (IFTA) (n = 2), renal vein thrombosis (n = 1), de novo glomerulopathy (n = 1), or primary nonfunction (n = 1). The 1- and 5-year patient and graft survival rates were 96% and 96%, 95% and 89%, respectively. We believe that exchange donor transplantation is as successful as direct transplants; it is a good, ethical alternative to unrelated living transplantations. Copyright © 2011 Elsevier Inc. All rights reserved.

Basiliximab induced non-cardiogenic pulmonary edema in two pediatric renal transplant recipients.

LENUS (Irish Health Repository)

Dolan, Niamh

2009-11-01

We report two cases of non-cardiogenic pulmonary edema as a complication of basiliximab induction therapy in young pediatric renal transplant patients identified following a retrospective review of all pediatric renal transplant cases performed in the National Paediatric Transplant Centre, Childrens University Hospital, Temple Street, Dublin, Ireland. Twenty-eight renal transplantations, of which five were living-related (LRD) and 23 were from deceased donors (DD), were performed in 28 children between 2003 and 2006. In six cases, transplantations were pre-emptive. Immunosuppression was induced pre-operatively using a combination of basiliximab, tacrolimus and methylprednisolone in all patients. Basiliximab induction was initiated 2 h prior to surgery in all cases and, in 26 patients, basiliximab was re-administered on post-operative day 4. Two patients, one LRD and one DD, aged 6 and 11 years, respectively, developed acute non-cardiogenic pulmonary edema within 36 h of surgery. Renal dysplasia was identified as the primary etiological factor for renal failure in both cases. Both children required assisted ventilation for between 4 and 6 days. While both grafts had primary function, the DD transplant patient subsequently developed acute tubular necrosis and was eventually lost within 3 weeks due to thrombotic microangiopathy and severe acute antibody-mediated rejection despite adequate immunosuppression. Non-cardiogenic pulmonary edema is a potentially devastating post-operative complication of basiliximab induction therapy in young pediatric patients following renal transplantation. Early recognition and appropriate supportive therapy is vital for patient and, where possible, graft survival.

Desensitization protocol enabling pediatric crossmatch-positive renal transplantation: successful HLA-antibody-incompatible renal transplantation of two highly sensitized children.

Science.gov (United States)

Adamusiak, Anna M; Stojanovic, Jelena; Shaw, Olivia; Vaughan, Robert; Sebire, Neil J; Drage, Martin; Kessaris, Nicos; Marks, Stephen D; Mamode, Nizam

2017-02-01

Renal transplantation improves quality of life (QoL) and survival in children requiring renal replacement therapy (RRT). Sensitization with development of a broad-spectrum of anti-HLA antibodies as a result of previous transplantation or after receiving blood products is an increasing problem. There are no published reports of desensitization protocols in children allowing renal transplantation from HLA-antibody-incompatible living donors. We adopted our well-established adult desensitization protocol for this purpose and undertook HLA antibody-incompatible living donor renal transplants in two children: a 14-year-old girl and a 13-year-old boy. After 2 and 1.5 years of follow-up, respectively, both patients have stable renal allograft function despite a rise in donor-specific antibodies in one case. HLA-incompatible transplantation should be considered in selected cases for sensitized children.

Past and Future Prospects of Orthoptic Liver Transplantation

OpenAIRE

Starzl, Thomas E.; Klintmalm, Goran B. G.; Iwatsuki, Shunzaburo; Fernandez-Bueno, Carlos

1981-01-01

The hopes for liver transplantation have been increased by experience with the new immunosuppresive drug cyclosporin A. Optimal therapy with cyclosporin A has required steroid therapy, but the amounts of prednisone used have been a small fraction of those used in the past.

Generation of Corneal Keratocytes from Human Embryonic Stem Cells.

Science.gov (United States)

Hertsenberg, Andrew J; Funderburgh, James L

2016-01-01

Human Embryonic Stem Cells (hESC) offer an important resource as a limitless supply of any differentiated cell type of the human body. Keratocytes, cells from the corneal stroma, may have the potential for restoration of vision in cell therapy and biomedical engineering applications, but these specialized cells are not readily expanded in vitro. Here we describe a two-part method to produce keratocytes from the H1 hESC cell line. The hESC cells, maintained and expanded in feeder-free culture medium are first differentiated to neural crest cells using the stromal-derived inducing activity (SDIA) of the PA6 mouse embryonic fibroblast cell line. The resulting neural crest cells are selected by their expression of cell-surface CD271 and subsequently cultured as 3D pellets in a defined differentiation medium to induce a keratocyte phenotype.

Percutaneous transluminal angioplasty (PTA) after kidney transplantation

International Nuclear Information System (INIS)

Fava, C.; Grosso, M.; Sandrone, M.; Malfi, B.; Segoloni, G.P.; Colla, L.

1988-01-01

Renal artery stenosis is a frequent complication of kidney transplantation (10%). Percutaneous transluminal angioplasty (PTA) has recently been proposed as a potential therapeutic procedure. Twelve transplant patients with arterial stenosis underwent PTA. The procedure was successful in 10 cases (83.3%). Restenosis occurred in 2 patients (16.7%); both of them underwent PTA successfully. No complications occurred. A considerable improvement in glomerular filtration rate and a reduction in high blood pressure were observed in all patients after successful PTA. The authors belive PTA to be the therapy of choice in the treatment of arterial stenoses in kidney transplant patients

Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

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Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

2014-12-01

A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients. Copyright© Ferrata Storti Foundation.

Is there a place for human fetal-derived stem cells for cell replacement therapy in Huntington's disease?

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Precious, Sophie V; Zietlow, Rike; Dunnett, Stephen B; Kelly, Claire M; Rosser, Anne E

2017-06-01

Huntington's disease (HD) is a neurodegenerative disease that offers an excellent paradigm for cell replacement therapy because of the associated relatively focal cell loss in the striatum. The predominant cells lost in this condition are striatal medium spiny neurons (MSNs). Transplantation of developing MSNs taken from the fetal brain has provided proof of concept that donor MSNs can survive, integrate and bring about a degree of functional recovery in both pre-clinical studies and in a limited number of clinical trials. The scarcity of human fetal tissue, and the logistics of coordinating collection and dissection of tissue with neurosurgical procedures makes the use of fetal tissue for this purpose both complex and limiting. Alternative donor cell sources which are expandable in culture prior to transplantation are currently being sought. Two potential donor cell sources which have received most attention recently are embryonic stem (ES) cells and adult induced pluripotent stem (iPS) cells, both of which can be directed to MSN-like fates, although achieving a genuine MSN fate has proven to be difficult. All potential donor sources have challenges in terms of their clinical application for regenerative medicine, and thus it is important to continue exploring a wide variety of expandable cells. In this review we discuss two less well-reported potential donor cell sources; embryonic germ (EG) cells and fetal neural precursors (FNPs), both are which are fetal-derived and have some properties that could make them useful for regenerative medicine applications. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Pegylated interferon alpha-2a and ribavirin combination therapy in HCV liver transplant recipients. Experience of 7 cases.

Science.gov (United States)

Iacob, Speranta; Gheorghe, Liana; Hrehoret, Doina; Becheanu, Gabriel; Herlea, Vlad; Popescu, Irinel

2008-06-01

Hepatitis C virus (HCV) related cirrhosis represents the leading indication for liver transplantation (LT) worldwide and HCV reinfection is the rule among transplant recipients. Combination therapy with interferon and ribavirin is the treatment of choice for established recurrent hepatitis C. To evaluate the efficacy and safety of the combination of pegylated interferon alpha-2a and ribavirin in LT recipients with histological recurrence of hepatitis C. Seven LT recipients with chronic hepatitis C recurrence were treated with peginterferon alpha-2a with an initial intended dose of 180 microg/week and an intended dose of ribavirin 800-1000 mg/day for at least 12 months and followed-up for at least 24 weeks. Early virological response rate was 57.1%. Three patients (42.8%) had end of treatment virological response and all had also sustained viral response (SVR). Five patients had end of treatment biological response, out of which 4 had also sustained biochemical response. Three patients had both SVR and sustained biochemical response. Four patients had end of treatment histological response, out of which 3 patients had also SVR. Cytopenia was the most common adverse event: anemia (57.1%), leucopenia/neutropenia (71.4%), thrombocytopenia (42.8%). Combination of pegylated interferon and ribavirin can be safely and successfully used in liver transplant recipients.

Association Between GLCCI1 Promoter Polymorphism (Rs37972 and Post-Transplant Hypertension in Renal Transplant Recipients

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Aki Mafune Hamada

2017-12-01

Full Text Available Background/Aims: Post-transplant hypertension is highly prevalent in renal transplant recipients and is a risk factor for graft loss, cardiovascular disease and death. Glucocorticoid is used to prevent rejection, but simultaneously increases the risk of post-transplant hypertension. The glucocorticoid-induced transcript 1 (GLCCI1 promoter polymorphism (rs37972 has been reported to be associated with response to glucocorticoid therapy in asthma. We therefore examined the association between GLCCI1 promoter polymorphism and post-transplant hypertension in renal transplant recipients. Methods: We conducted a retrospective cohort study of renal transplantation at a single university hospital from October 2003 to January 2014. Fifty consecutive adult recipients were analyzed, with clinical data retrieved from a prospectively collected database. Genotyping was carried out using genomic DNA derived from recipient’s blood. GLCCI1 immunoreactivity in vascular endothelial cells was quantitatively analyzed by immunohistochemical staining of recipients’ native kidney biopsy-specimens. The primary outcome measure was post-transplant hypertension. Results: Post-transplant hypertension was observed in 14/17 (82% of recipients with CC, 18/20 (90% with CT, and 2/13 (15% with TT genotype. CC/CT genotype was significantly associated with post-transplant hypertension, even after adjustment for covariates (odds ratio, 10.6; 95% confidence intervals, 1.32 to 85.8; P = 0.026. In addition, we observed that GLCCI1 immunoreactivity in arteriolar endothelial cells was higher in kidney specimens obtained from recipients with a CC/CT genotype than a TT genotype (P = 0.021. Conclusion: GLCCI1 promoter polymorphism rs37972 may be associated with post-transplant hypertension.

Renal transplant scintigraphy (Part 1)

International Nuclear Information System (INIS)

Chew, Ghee

2005-01-01

Renal transplantation is the most effective mode of renal replacement therapy for correction of renal failure. Renal donors can either be: a. a deceased person - the kidneys being removed when brain death or absence of cerebral cortical function / perfusion is confirmed - the cadaveric kidney is packed in ice and nutrient solution and transplanted within 24 hours of removal ('cold ischemia') ob. a living donor - the donor may or may not be related to the recipient. Due to the limited length of the renal vessels and ureter of the donor kidney, it is implanted close to the bladder of the recipient. The donor vessels are anastomosed to the iliac artery and vein of the recipient. Transplant variants: a. 2 kidneys maybe transplanted because: - an old donor with less kidney reserve from atrophy due to age or disease (e.g. hypertension) - an infant donor when both kidneys are removed en bloc, b. Donor kidneys with more than 1 artery, vein or ureter. c. Donor horse shoe kidney d. Combined renal and pancreas transplant for type I diabetics -a short segment of duodenum transplanted with the pancreas maybe implanted into the bladder. Copyright (2005) The Australian and New Zealand Society of Nuclear Medicine

Desensitization strategies in adult heart transplantation-Will persistence pay off?

Science.gov (United States)

Chih, Sharon; Patel, Jignesh

2016-08-01

Strategies are needed to enable successful heart transplantation in highly sensitized patients. Immunologic challenges from sensitization to human leukocyte antigen (HLA) reduce access to compatible donors, extend waiting times to transplant, and increase the risks of antibody-mediated rejection and cardiac allograft vasculopathy after transplant. The prime goal of desensitization is to increase access to transplantation through expansion of the donor organ pool. Existing therapies are directed at key components of the humoral immune response with newer biologically based regimens able to target plasma cells as the source of antibody production, as well as complement activation that has a central role in antibody-mediated injury. Despite the emergence of early promising results for these agents, a significant knowledge gap remains with the current data for desensitization, extrapolated mostly from non-heart solid-organ transplants and small observational studies. Notably, no approach has demonstrated significant and sustainable reductions in HLA antibody pre-transplant, and the ideal desensitization strategy remains elusive. In addition, clinical tools to evaluate the humoral response and efficacy of therapy are limited, focusing almost exclusively on HLA antibody detection. Importantly, desensitization is associated with significant costs and potential risks, and overall long-term outcomes and cost-effectiveness have not been sufficiently evaluated. Investigation is ongoing into the development of a clinically effective desensitization strategy in heart transplantation. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Protothecal bursitis after simultaneous kidney/liver transplantation: a case report and review.

Science.gov (United States)

Ramírez, I; Nieto-Ríos, J F; Ocampo-Kohn, C; Aristizábal-Alzate, A; Zuluaga-Valencia, G; Muñoz Maya, O; Pérez, J C

2016-04-01

Solid organ transplantation is an accepted therapy for end-stage diseases of the kidneys, liver, heart, and lungs. Unfortunately, transplantation is associated with infectious complications. Here, we present a case report of Prototheca wickerhamii olecranon bursitis and review all of the cases in solid organ transplant (SOT) recipients published in the literature to date. In our patient, the infection resolved with surgical therapy and limited antifungal therapy, and no symptoms have recurred over 24 months of follow-up. A review of the literature suggests that 50% of SOT recipients with Prototheca infection present with disseminated infection, and the overall mortality is 75%. More studies are required to determine the optimal management of protothecosis in this population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

No major neurologic complications with sirolimus use in heart transplant recipients

NARCIS (Netherlands)

van de Beek, Diederik; Kremers, Walter K.; Kushwaha, Sudhir S.; McGregor, Christopher G. A.; Wijdicks, Eelco F. M.

2009-01-01

OBJECTIVE: To determine whether sirolimus therapy is associated with neurologic complications, including stroke, among heart transplant recipients. PATIENTS AND METHODS: We retrospectively studied patients who underwent heart transplant at Mayo Clinic's site in Rochester, MN, from January 1, 1988,

Influenza in solid organ transplant recipients.

Science.gov (United States)

Martin, Spencer T; Torabi, Mina J; Gabardi, Steven

2012-02-01

To review available data describing the epidemiology, outcomes, prevention, and treatment of influenza virus in the solid organ transplant population and to evaluate the strengths and limitations of the current literature, with a focus on literature reviewing annual influenza strains and the recent pandemic novel influenza A/H1N1 strain. A systematic literature search (July 1980-June 2011) was performed via PubMed using the following key words: influenza, human; influenza; novel influenza A H1/N1; transplantation; solid organ transplantation; kidney transplant; renal transplant; lung transplant; heart transplant; and liver transplant. Papers were excluded if they were not written in English or were animal studies or in vitro studies. Data from fully published studies and recent reports from international conferences were included. The influenza virus presents a constant challenge to immunocompromised patients and their health care providers. The annual influenza strain introduces a highly infectious and pathogenic risk to solid organ transplant recipients. In 2009, the World Health Organization declared a pandemic as a result of a novel influenza A/H1N1 strain. The pandemic introduced an additional viral threat to solid organ transplant patients at increased risk for infectious complications. The mainstay for prevention of influenza infection in all at-risk populations is appropriate vaccination. Antiviral therapies against influenza for chemoprophylaxis and treatment of infection are available; however, dosing strategies in the solid organ transplant population are not well defined. The solid organ transplant population is at an increased risk of severe complications from influenza infection. Identifying risks, preventing illness, and appropriately treating active infection is essential in this patient population.

[Kidney transplantation epidemiology in France].

Science.gov (United States)

Hiesse, Christian

2013-11-01

Kidney transplantation activity in France is among the most important worldwide: in 2011, 2976 transplants have been performed (47.5 per million population), and the number of patients living with a functional graft is estimated around 30,000, representing 44.7% of all patients (n = 67,270) treated for end-stage renal failure. However, the rate of preemptive kidney transplants remains very low, only 3.3% of incident patients starting renal replacement therapy. The analysis of demand showed a progressive increase in recent years, as demonstrated by the registration rate on the kidney transplantation waiting list, increasing by 5% yearly between 2006 and 2010, but with huge differences according to age categories and regional registration areas, reflecting discrepant appreciations in indications for kidney transplantation. The median waiting time between registration and transplantation increased progressively in recent years, reaching 22.3 months with considerable variations according to regional areas and transplantation teams. Kidney transplantation activity, while increasing continuously, is far to cover the rising demand, and inexorably patients accumulate on the waiting list (around 9000 patients were registered by January 2012). This situation is the consequence of insufficient organ procurement activity. The deceased organ procurement rate remained high: 1572 harvested donors in 2011 (24.1 per million population), but the proportion of older donors rose in recent years, to reach the rate of 26% of donors older than 65 years in 2011. The procurement activity of donors after cardiac arrest was reintroduced in 2006, but increased slowly: 65 transplants were performed in 2011 using kidney procured in non heart-beating donors. The living donor kidney transplantation activity has markedly increased recently: 302 living donor transplantations were performed in 2011, representing 10.1% of the kidney transplantations. Facing the predictable increase in the number of

Aplasia medular após transplante hepático em pediatria Aplastic anemia after pediatric liver transplantation

Directory of Open Access Journals (Sweden)

Marlene P. Garanito

2009-01-01

Full Text Available A aplasia de medula é uma das mais raras (Aplastic anemia (AA is one of the rarest (<1% and most serious complications of liver transplantation for fulminant non-A, non-B and non-C hepatitis. It was first described in 1987 by Stock; the mechanism involved is an immunologically mediated condition secondary to an unknown viral infection. The disease is associated with a dismal prognosis. Spontaneous recovery from acquired AA is very rare however some patients (50-70% recover after immunosuppressive therapy, such as Cyclosporin A (CsA and Antithymocyte globulin (ATG, even after liver transplantation. Another treatment option is bone marrow transplantation. We report on a child who developed AA following liver transplantation for fulminant viral hepatitis that was treated with intensive immunosuppression including CsA and ATG and achieved complete recovery.

Function of external respiration in patients after kidney transplantation under conditions of immunosuppressive therapy.

Directory of Open Access Journals (Sweden)

O. V. Kuryata

2018-04-01

Full Text Available The aim of our study was to evaluate the changes in the parameters of the function of external respiration in patients after kidney transplantation due to chronic kidney disease and to assess the relationship between the level of cyclosporin A and tacrolimus in the blood with FVD indices. The study included 37 patients after kidney transplantation. The first group included 27 patients who received cyclosporine at an average dose of 225 [175-350] mg/day under the immunosuppressive therapy regimen, the second group included 10 patients who received tacrolimus at an average dose of 8.25 [5.0-9.0] mg/day. A significant difference (p˂0.05 between the indicators of the VCmax (78 [71-90]% and 76.5 [72-78]%, FVC (93 [85-99]% and 95 [91-98]%, PEF (82 [64-94]% and 80 [69-84]%, MEF25-75 (75 [66-112]% and 82.5 [67-90]% was found in patients of the first and second groups relative to the FVD of the comparison group: VCmax (102.5 [98-113]%, FVC (107.5 [105.5-124]%, PEF (99.5 [95-102.5]%, MEF25-75 (98.5 [97.5-101.5]%. In both groups, a statistically significant negative correlation between the indicators of the VCmax, FVC and the level of cyclosporin A (R=-0.69, p<0.0001 and R=-0.4, p<0.037 in the blood in the first group and FVC and tacrolimus (R=-0.72, p<0.018 in the second group was found. A moderate decrease in the VCmax values in patients after kidney transplantation requires monitoring of the function of external respiration and managing such patients by nephrologists together with specialists in the pulmonological profile.

Beta-Cell Replacement: Pancreas and Islet Cell Transplantation.

Science.gov (United States)

Niclauss, Nadja; Meier, Raphael; Bédat, Benoît; Berishvili, Ekaterine; Berney, Thierry

2016-01-01

Pancreas and islet transplantation are 2 types of beta-cell replacement therapies for type 1 diabetes mellitus. Since 1966, when pancreas transplantation was first performed, it has evolved to become a highly efficient procedure with high success rates, thanks to advances in surgical technique and immunosuppression. Pancreas transplantation is mostly performed as simultaneous pancreas-kidney transplantation in patients with end-stage nephropathy secondary to diabetes. In spite of its efficiency, pancreas transplantation is still a major surgical procedure burdened by high morbidity, which called for the development of less invasive and hazardous ways of replacing beta-cell function in the past. Islet transplantation was developed in the 1970s as a minimally invasive procedure with initially poor outcomes. However, since the report of the 'Edmonton protocol' in 2000, the functional results of islet transplantation have substantially and constantly improved and are about to match those of whole pancreas transplantation. Islet transplantation is primarily performed alone in nonuremic patients with severe hypoglycemia. Both pancreas transplantation and islet transplantation are able to abolish hypoglycemia and to prevent or slow down the development of secondary complications of diabetes. Pancreas transplantation and islet transplantation should be seen as two complementary, rather than competing, therapeutic approaches for beta-cell replacement that are able to optimize organ donor use and patient care. © 2016 S. Karger AG, Basel.

Advances in Cell Transplantation Therapy for Diseased Myocardium

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Outi M. Villet

2011-01-01

Full Text Available The overall objective of cell transplantation is to repopulate postinfarction scar with contractile cells, thus improving systolic function, and to prevent or to regress the remodeling process. Direct implantation of isolated myoblasts, cardiomyocytes, and bone-marrow-derived cells has shown prospect for improved cardiac performance in several animal models and patients suffering from heart failure. However, direct implantation of cultured cells can lead to major cell loss by leakage and cell death, inappropriate integration and proliferation, and cardiac arrhythmia. To resolve these problems an approach using 3-dimensional tissue-engineered cell constructs has been investigated. Cell engineering technology has enabled scaffold-free sheet development including generation of communication between cell graft and host tissue, creation of organized microvascular network, and relatively long-term survival after in vivo transplantation.

Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

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Bryant, Jane; Hlavaty, Kelan A; Zhang, Xiaomin; Yap, Woon-Teck; Zhang, Lei; Shea, Lonnie D; Luo, Xunrong

2014-10-01

Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation

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Yoshinobu Takahashi

2018-05-01

Full Text Available Summary: Clinical transplantation of tissue fragments, including islets, faces a critical challenge because of a lack of effective strategies that ensure efficient engraftment through the timely integration of vascular networks. We recently developed a complex organoid engineering method by “self-condensation” culture based on mesenchymal cell-dependent contraction, thereby enabling dissociated heterotypic lineages including endothelial cells to self-organize in a spatiotemporal manner. Here, we report the successful adaptation of this method for generating complex tissues from diverse tissue fragments derived from various organs, including pancreatic islets. The self-condensation of human and mouse islets with endothelial cells not only promoted functionalization in culture but also massively improved post-transplant engraftment. Therapeutically, fulminant diabetic mice were more efficiently treated by a vascularized islet transplant compared with the conventional approach. Given the general limitations of post-transplant vascularization associated with 3D tissue-based therapy, our approach offers a promising means of enhancing efficacy in the context of therapeutic tissue transplantation. : Takahashi et al. report on generating vascularized islet tissue from humans and mice. After transplantation, vascularized islets significantly improve survival of diabetic mice, demonstrating the quick normalization of blood glucose compared with conventional islet transplantation. Keywords: tissue engineering, tissue-based therapy, vascularization, islet transplantation, organoid

Cytomegalovirus infection in the bone marrow transplant patient.

Science.gov (United States)

Bhat, Vivek; Joshi, Amit; Sarode, Rahul; Chavan, Preeti

2015-12-24

Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear.

Current issues in allogeneic islet transplantation.

Science.gov (United States)

Chang, Charles A; Lawrence, Michael C; Naziruddin, Bashoo

2017-10-01

Transplantation of allogenic pancreatic islets is a minimally invasive treatment option to control severe hypoglycemia and dependence on exogenous insulin among type 1 diabetes (T1D) patients. This overview summarizes the current issues and progress in islet transplantation outcomes and research. Several clinical trials from North America and other countries have documented the safety and efficacy of clinical islet transplantation for T1D patients with impaired hypoglycemia awareness. A recently completed phase 3 clinical trial allows centres in the United States to apply for a Food and Drug Administration Biologics License for the procedure. Introduction of anti-inflammatory drugs along with T-cell depleting induction therapy has significantly improved long-term function of transplanted islets. Research into islet biomarkers, immunosuppression, extrahepatic transplant sites and potential alternative beta cell sources is driving further progress. Allogeneic islet transplantation has vastly improved over the past two decades. Success in restoration of glycemic control and hypoglycemic awareness after islet transplantation has been further highlighted by clinical trials. However, lack of effective strategies to maintain long-term islet function and insufficient sources of donor tissue still impose limitations to the widespread use of islet transplantation. In the United States, wide adoption of this technology still awaits regulatory approval and, importantly, a financial mechanism to support the use of this technology.

Management of Portal Hypertension After Liver Transplantation.

Science.gov (United States)

Korda, D; Deák, P Á; Kiss, G; Gerlei, Z; Kóbori, L; Görög, D; Fehérvári, I; Piros, L; Máthé, Z; Doros, A

2017-09-01

Post-transplantation portal hypertension has severe complications, such as esophageal varix bleeding, therapy refractory ascites, extreme splenomegaly, and graft dysfunction. The aim of our study was to analyze the effectiveness of the therapeutic strategies and how to visualize the procedure. A retrospective study involving liver transplantation patients from the Semmelweis University Department of Transplantation and Surgery was performed between 2005 and 2015. The prevalence, etiology, and leading complications of the condition were determined. The applied interventions' effects on the patients' ascites volume, splenic volume, and the occurrence of variceal bleeding were determined. Mean portal blood flow velocity and congestion index values were calculated using Doppler ultrasonography. The prevalence of post-transplantation portal hypertension requiring intervention was 2.8%. The most common etiology of the disease was portal anastomotic stenosis. The most common complications were esophageal varix bleeding and therapy refractory ascites. The patients' ascites volume decreased significantly (2923.3 ± 1893.2 mL vs. 423.3 ± 634.3 mL; P portal hypertension. After the interventions, these parameters shifted towards the physiologic ranges. The interventions performed in our clinic were effective in most cases. The patients' ascites volume, splenic volume, and the prevalence of variceal bleeding decreased after the treatment. Doppler ultrasonography has proved to be a valuable imaging modality in the diagnosis and the follow-up of post-transplantation portal hypertension. Copyright © 2017 Elsevier Inc. All rights reserved.

[An artificial heart: bridge to transplantation or permanent?].

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de Mol, Bas A J M; Lahpor, Jaap

2013-01-01

An artificial heart is a continuous-flow pump device with a constant output, which usually supports the left ventricle. Over the past five years, survival rates with an artificial heart have increased dramatically, but with an annual mortality of 10% per year compared with 6% for heart transplantation the artificial heart is mainly a 'bridge to transplantation' or an alternative for those patients who are not suitable for heart transplant, 'destination therapy'. It is anticipated that the number and severity of complications will decrease as a result of technological progress. The artificial heart could then become a long-term treatment option providing a good quality of life and thus become equivalent to a heart transplant.

Female qualities in males: vitellogenin synthesis induced by ovary transplants into the male silkworm, Bombyx mori.

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Yang, Congwen; Lin, Ying; Shen, Guanwang; Chen, Enxiang; Wang, Yanxia; Luo, Juan; Zhang, Haiyan; Xing, Runmiao; Xia, Qingyou

2014-10-10

Female qualities in males are common in vertebrates but have not been extensively reported in insects. Vitellogenin (Vg) is highly expressed in the female fat body and is generally required for the formation of yolk proteins in the insect egg. Vg upregulation is generally regarded as a female quality in female oviparous animals. In this study, we found that Bombyx mori Vg (BmVg) is especially highly expressed in the female pupa. Downregulation of the BmVg gene in the female pupa by RNA interference (RNAi) interfered with egg formation and embryonic development, showing the importance of BmVg in these processes. So, we used BmVg as a biomarker for female qualities in the silkworm. Hematoxylin-eosin staining and immunofluorescence histochemistry showed that ovary transplants induced BmVg synthesis in the male pupa fat body. Ovaries transplanted into male silkworms produced only a few eggs with deformed yolk granules. These results suggested that the amount of BmVg in the male silkworm was insufficient for eggs to undergo complete embryonic development. After 17-beta-estradiol was used to treat male pupae and male pupal fat bodies, BmVg was upregulated in vivo and in vitro. These findings indicated that the male silkworm has innate female qualities that were induced by a transplanted ovary and 17β-estradiol. However, in silkworms, female qualities in males are not as complete as in females. Copyright © 2014 Elsevier Inc. All rights reserved.

Synthetic niches for differentiation of human embryonic stem cells bypassing embryoid body formation.

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Liu, Yarong; Fox, Victoria; Lei, Yuning; Hu, Biliang; Joo, Kye-Il; Wang, Pin

2014-07-01

The unique self-renewal and pluripotency features of human embryonic stem cells (hESCs) offer the potential for unlimited development of novel cell therapies. Currently, hESCs are cultured and differentiated using methods, such as monolayer culture and embryoid body (EB) formation. As such, achieving efficient differentiation into higher order structures remains a challenge, as well as maintaining cell viability during differentiation into homogeneous cell populations. Here, we describe the application of highly porous polymer scaffolds as synthetic stem cell niches. Bypassing the EB formation step, these scaffolds are capable of three-dimensional culture of undifferentiated hESCs and subsequent directed differentiation into three primary germ layers. H9 hESCs were successfully maintained and proliferated in biodegradable polymer scaffolds based on poly (lactic-co-glycolic acid) (PLGA). The results showed that cells within PLGA scaffolds retained characteristics of undifferentiated pluripotent stem cells. Moreover, the scaffolds allowed differentiation towards the lineage of interest by the addition of growth factors to the culture system. The in vivo transplantation study revealed that the scaffolds could provide a microenvironment that enabled hESCs to interact with their surroundings, thereby promoting cell differentiation. Therefore, this approach, which provides a unique culture/differentiation system for hESCs, will find its utility in various stem cell-based tissue-engineering applications. © 2013 Wiley Periodicals, Inc.

Impact of long term left ventricular assist device therapy on donor allocation in cardiac transplantation.

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Uriel, Nir; Jorde, Ulrich P; Woo Pak, Sang; Jiang, Jeff; Clerkin, Kevin; Takayama, Hiroo; Naka, Yoshifumi; Schulze, P Christian; Mancini, Donna M

2013-02-01

Left Ventricular Assist Devices (LVAD) are increasingly used as a bridge to transplant (BTT) for patients with advanced congestive heart failure (CHF) and are assigned United Network for Organ Sharing (UNOS) high priority status (1B or 1A). The purpose of our study was asses the effect of organ allocation in the era of continuous flow pumps. A retrospective chart review was performed of all patients transplanted between 1/2001-1/2011 at Columbia University Medical Center. Seven hundred twenty six adult heart transplantations were performed. Two hundred seventy four BTT patients were implanted with LVAD; of which 227 patients were transplanted. Sixty three patients were transplanted as UNOS-1B, while 164 were transplanted as UNOS-1A (72%). Of these 164 patients, 65 were transplanted during their 30-day 1A period (43%) and 96 after upgrading to UNOS-1A for device complication (56%). For 452 non-device patients 139 (31%) were transplanted as UNOS-1A, 233 as UNOS-1B (52%), and 80 as UNOS-2 (17%). The percentage of patients bridged with LVAD increased from 19% in 2001 to 64% in 2010 while the number transplanted during their 30 day 1A grace period declined from 57% in 2005 to 16% in 2011; i.e. 84% of BTT patients in 2011 needed more than 30 days 1A time to be transplanted. Most LVAD patients are now transplanted while suffering device complication. There was no difference in post transplant survival between LVAD patients transplanted as UNOS 1B, 1A grace period or for a device complication As wait time for cardiac transplantation increased the percentage of patients being bridged to transplant with an LVAD has increased with the majority of them transplanted in the setting of device complication. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Cadaveric domino liver transplantation: the first case in Japan.

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Wakayama, Kenji; Jin, Maeng Bong; Furukawa, Hiroyuki; Todo, Satoru; Shimamura, Tsuyoshi; Suzuki, Tomomi; Hattori, Masahiro; Yokoyama, Ryouji; Iwasaki, Sari; Sato, Masanori; Nakagawa, Takahito; Kurauchi, Noriaki; Kamachi, Hirohumi; Kamiyama, Toshiya; Matsushita, Michiaki

2004-01-01

The first case of domino liver transplantation from a brain-dead donor in Japan is described. A 49-year-old man with familial amyloidotic polyneuropathy received a cadaver liver, and his native liver was transplanted into a 53-year-old man with polycystic liver and kidney disease. The cadaveric liver allograft was transplanted by the conventional technique. The graft taken from the first recipient had four outflow orifices (the left, middle, and right hepatic veins, and upper vena cava), for which a single orifice was created at the back table. This graft was transplanted in piggy-back fashion. The first recipient developed acute rejection on day 13 and hepatic artery stenosis on day 36. These were treated by steroid recycle therapy and percutaneous transarterial angioplasty. He was discharged on day 57 with normal liver function. The second recipient underwent re-operation for bleeding from the right adrenal gland and left thoracic cavity. He was diagnosed with acute rejection on day 7, which was treated by steroid pulse therapy. He was discharged uneventfully on day 39 with normal liver function.

Management Strategies for Posttransplant Diabetes Mellitus after Heart Transplantation: A Review

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Matthew G. Cehic

2018-01-01

Full Text Available Posttransplant diabetes mellitus (PTDM is a well-recognized complication of heart transplantation and is associated with increased morbidity and mortality. Previous studies have yielded wide ranging estimates in the incidence of PTDM due in part to variable definitions applied. In addition, there is a limited published data on the management of PTDM after heart transplantation and a paucity of studies examining the effects of newer classes of hypoglycaemic drug therapies. In this review, we discuss the role of established glucose-lowering therapies and the rationale and emerging clinical evidence that supports the role of incretin-based therapies (glucagon like peptide- (GLP- 1 agonists and dipeptidyl peptidase- (DPP- 4 inhibitors and sodium-glucose cotransporter 2 (SGLT2 inhibitors in the management of PTDM after heart transplantation. Recently published Consensus Guidelines for the diagnosis of PTDM will hopefully lead to more consistent approaches to the diagnosis of PTDM and provide a platform for the larger-scale multicentre trials that will be needed to determine the role of these newer therapies in the management of PTDM.

Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors

International Nuclear Information System (INIS)

Odagiri, Kazumasa; Omura, Motoko; Hata, Masaharu; Aida, Noriko; Niwa, Tetsu; Goto, Hiroaki; Ito, Susumu; Adachi, Masanori; Yoshida, Haruyasu; Yuki, Hiroko; Inoue, Tomio

2014-01-01

Standard treatment strategies for embryonal central nervous system (CNS) tumors have not yet been established. We treated these tumors using an original chemoradiation therapy protocol; the clinical outcomes and toxicities were retrospectively evaluated. Twenty-four patients were enrolled including sixteen with medulloblastoma, four with supratentorial primitive neuroectodermal tumor (sPNET), three with atypical teratoid/rhabdoid tumor, and one with pineoblastoma. Immediately after diagnosis, all patients underwent surgery initially. They were then categorized as high- or average-risk groups independent of tumor type/pathogenesis. The average-risk group included patients who were aged ≥3 years at diagnosis, had non-metastatic disease at diagnosis (M0), and had undergone gross total resection. Other patients were categorized as the high-risk group; this group received more intensive treatment than the average-risk group, including high-dose chemotherapy with autologous stem-cell transplantation. All patients received craniospinal irradiation (CSI). The CSI dose was 23.4 Gy for M0 patients aged ≥5 years, 18 Gy for M0 patients aged <5 years, and 30–36 Gy for all patients with M + disease. The total dose to the primary tumor bed was 54 Gy. The median follow-up time was 73.5 (range, 19–118) months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 71.1 and 88.9%, respectively in the average-risk group (n = 9) and 66.7 and 71.1%, respectively in the high-risk group (n = 15). The PFS and OS rates were not significantly different between the average- and high-risk groups. In patients with medulloblastoma only, these rates were also not significantly different between the average- and high-risk groups. Three of four patients with sPNET were disease free. The height standard deviation score (SDS) was significantly decreased at the last assessment relative to that at diagnosis (P < 0.0001). The latest median height SDS was -1.6 (range, 0

Pancreas Islet Transplantation for Patients With Type 1 Diabetes Mellitus: A Clinical Evidence Review.

Science.gov (United States)

2015-01-01

intensive insulin therapy. For patients without kidney disease, islet transplantation improves glycemic control and diabetic complications for patients with type 1 diabetes when compared with intensive insulin therapy. However, results for health-related quality of life outcomes were mixed, and adverse events were increased compared with intensive insulin therapy. For patients with type 1 diabetes with kidney disease, islet-after-kidney transplantation or simultaneous islet-kidney transplantation also improved glycemic control and secondary diabetic complications, although the evidence was more limited for this patient group. Compared with intensive insulin therapy, adverse events for islet-after-kidney transplantation or simultaneous islet-kidney transplantation were increased, but were in general less severe than with whole pancreas transplantation. For patients with type 1 diabetes with difficult-to-control blood glucose levels, islet transplantation may be a beneficial β-cell replacement therapy to improve glycemic control and secondary complications of diabetes. However, there is uncertainty in the estimates of effectiveness because of the generally low to very low quality of evidence for all outcomes of interest.

Combination of heterologous fibrin sealant and bioengineered human embryonic stem cells to improve regeneration following autogenous sciatic nerve grafting repair.

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Mozafari, Roghayeh; Kyrylenko, Sergiy; Castro, Mateus Vidigal; Ferreira, Rui Seabra; Barraviera, Benedito; Oliveira, Alexandre Leite Rodrigues

2018-01-01

Peripheral nerve injury is a worldwide clinical problem, and the preferred surgical method for treating it is the end-to-end neurorrhaphy. When it is not possible due to a large nerve gap, autologous nerve grafting is used. However, these surgical techniques result in nerve regeneration at highly variable degrees. It is thus very important to seek complementary techniques to improve motor and sensory recovery. One promising approach could be cell therapy. Transplantation therapy with human embryonic stem cells (hESCs) is appealing because these cells are pluripotent and can differentiate into specialized cell types and have self-renewal ability. Therefore, the main objective of this study was to find conditions under which functional recovery is improved after sciatic nerve neurorrhaphy. We assumed that hESC, either alone or in combination with heterologous fibrin sealant scaffold, could be used to support regeneration in a mouse model of sciatic nerve injury and repair via autografting with end-to-end neurorrhaphy. Five millimeters of the sciatic nerve of C57BL/6 J mice were transected off and rotated 180 degrees to simulate an injury, and then stumps were sutured. Next, we applied heterologous fibrin sealant and/or human embryonic stem cells genetically altered to overexpress fibroblast growth factor 2 (FGF2) at the site of the injury. The study was designed to include six experimental groups comprising neurorrhaphy (N), neurorrhaphy + heterologous fibrin sealant (N + F), neurorrhaphy + heterologous fibrin sealant + doxycycline (N + F + D), neurorrhaphy + heterologous fibrin sealant + wild-type hESC (N + F + W), neurorrhaphy + heterologous fibrin sealant + hESC off (N + F + T), and neurorrhaphy + heterologous fibrin sealant + hESC on via doxycycline (N + F + D + T). We evaluated the recovery rate using Catwalk and von Frey functional recovery tests, as well as immunohistochemistry analysis. The experiments indicated that

nduced pluripotent stem cells and cell therapy

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Banu İskender

2013-12-01

Full Text Available Human embryonic stem cells are derived from the inner cell mass of a blastocyst-stage embryo. They hold a huge promise for cell therapy with their self-renewing ability and pluripotency, which is known as the potential to differentiate into all cell types originating from three embryonic germ layers. However, their unique pluripotent feature could not be utilised for therapeutic purposes due to the ethical and legal problems during derivation. Recently, it was shown that the cells from adult tissues could be reverted into embryonic state, thereby restoring their pluripotent feature. This has strenghtened the possiblity of directed differentition of the reprogrammed somatic cells into the desired cell types in vitro and their use in regenerative medicine. Although these cells were termed as induced pluripotent cells, the mechanism of pluripotency has yet to be understood. Still, induced pluripotent stem cell technology is considered to be significant by proposing novel approaches in disease modelling, drug screening and cell therapy. Besides their self-renewing ability and their potential to differentiate into all cell types in a human body, they arouse a great interest in scientific world by being far from the ethical concerns regarding their embryonic counterparts and their unique feature of being patient-specific in prospective cell therapies. In this review, induced pluripotent stem cell technology and its role in cell-based therapies from past to present will be discussed. J Clin Exp Invest 2013; 4 (4: 550-561

Diagnosis and treatment of spinal tuberculosis after liver transplantation

Institute of Scientific and Technical Information of China (English)

Peng-Cheng Gu; Rong-Huan Wu; Xiang-Jin Lin

2009-01-01

BACKGROUND: Spinal tuberculosis is a common disease in orthopedic clinical practice; however, it is seldom reported after organ transplantation. The aim of this study was to investigate the diagnosis and treatment of spinal tuberculosis after organ transplantation. METHOD: Two cases were diagnosed as spinal tuberculosis after liver transplantation and were treated with socarboxazide, rifampicin, streptomycin and ethambutol for more than one year. RESULTS: After treatment with anti-tuberculosis drugs for several months, the symptoms of both patients clearly improved. Back pain disappeared, and erythrocyte sedimentation and body temperature returned to normal. CONCLUSIONS: We should highly suspect spinal tuberculosis if notalgia and night sweats are present after organ transplantation. Anti-tuberculosis therapy is an effective treatment for spinal tuberculosis after organ transplantation.

Advanced pulmonary arterial hypertension: mechanical support and lung transplantation

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Sonja Bartolome

2017-12-01

Full Text Available The development of targeted therapies has transformed the outlook for patients with pulmonary arterial hypertension (PAH; however, some patients fail to achieve an adequate clinical response despite receiving maximal treatment. For these patients, lung transplantation remains an important therapeutic option, and recommendations for transplantation are included in the current European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension. Although lung transplantation is not without risk, overall long-term survival rates are good and substantial improvements in quality of life have been reported for lung transplant recipients. In this review, we describe the important considerations prior to, during and after transplantation, including the role of mechanical support, in patients with advanced PAH.

Combination antifungal therapy and surgery for the treatment of invasive pulmonary aspergillosis after hematopoietic stem cell transplantation

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Tiziana Toffolutti

2011-06-01

Full Text Available An 8-year old boy, affected by severe aplastic anemia, developed a probable pulmonary invasive aspergillosis (IA early after a second unrelated allogeneic hematopoietic stem cell transplant (HSCT. He was treated promptly with the combination of liposomal amphotericin B and caspofungin. Despite the initial stabilization, the patient deteriorated and the antifungal therapy was switched to voriconazole and caspofungin. The patient gradually improved and was discharged home on day +29 post-HSCT on oral voriconazole. On day +119, a sudden episode of hemoptysis occurred and a right superior lobectomy was decided to remove the residual aspergilloma. The patient is now alive and well more than 24 months from HSCT. This case demonstrated that antifungal combination therapy and surgery are valid options to cure pulmonary IA even in patients at high-risk and severely immunosuppressed.

[Heart transplant in "Nuevo Leon": the first 33 cases].

Science.gov (United States)

Herrera Garza, Eduardo; Molina Gamboa, Julio; Decanini Arcaute, Horacio; Ibarra Flores, Marcos; Torres García, Myrella; Macías Hidalgo, Carlos; González Oviedo, Roberto; de la Fuente Magallanes, Felipe de Jesús; Elizondo Sifuentes, Lius Angel; Villarreal Arredondo, Miguel Angel; Ortega Durán, Oscar; Martínez Bermúdez, Pedro; García Castillo, Armando; Becerra García, Oralia; Martínez Rodríguez, Diana; Contreras Lara, Carmen; Olivares de la Cerda, María de Consuelo; Treviño Treviño, Alfonso

2006-01-01

Heart failure is one of the most important causes of death worldwide. Heart transplant is the last effective alternative when the medical and surgical treatments have failed in patients with end stage heart failure, giving them an 80% one year survival rate. Unfortunately, during the outcome, the heart transplant patients can develop complications such as graft rejection and opportunistic infections because of the use of immunosuppressive therapy. In the present article we report the experience with 33 heart transplant patients. Our program not only has successfully transplanted patients with advanced age but, for the first time in Latin America we have transplanted patients assisted with the ambulatory Thoratec TLC II system. Even with limited resources, we have managed the same complications than other heart transplant programs, our 82% one year survival rate is similar than reports in medical literature.

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation.

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Thomson, Angus W; Zahorchak, Alan F; Ezzelarab, Mohamed B; Butterfield, Lisa H; Lakkis, Fadi G; Metes, Diana M

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

Treatment of advanced rectal cancer after renal transplantation

Institute of Scientific and Technical Information of China (English)

Hai-Yi Liu; Xiao-Bo Liang; Yao-Ping Li; Yi Feng; Dong-Bo Liu; Wen-Da Wang

2011-01-01

Renal transplantation is a standard procedure for end-stage renal disease today. Due to immunosuppressive drugs and increasing survival time after renal trans-plantation, patients with transplanted kidneys carry an increased risk of developing malignant tumors. In this case report, 3 patients with advanced rectal can-cer after renal transplantation for renal failure were treated with anterior resection or abdominoperineal resection plus total mesorectal excision, followed by adjuvant chemotherapy. One patient eventually died of metastasized cancer 31 mo after therapy, although his organ grafts functioned well until his death. The other 2 patients were well during the 8 and 21 mo follow-up periods after rectal resection. We therefore strongly argue that patients with advanced rectal cancer should receive standard oncology treatment, including opera-tion and adjuvant treatment after renal transplantation. Colorectal cancer screening in such patients appears justified.

Kidney transplantation and hyperparathyroidism

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O. N. Vetchinnikova

2017-01-01

Full Text Available Successful kidney transplantation eliminates endocrine and metabolic disorders that predispose to the development of hyperparathyroidism, the complication typical for the chronic kidney disease; but the process of recovery from mineral and bone disorders is slowed down. The highest incidence of post-transplant hyperparathyroidism is recorded in the first postoperative year. The risk factors for its development or persistence include the high blood levels of parathyroid hormone, calcium, phosphorus, and/or alkaline phosphatase, a prolonged dialysis therapy, severe hyperparathyroidism in the preoperative period, vitamin D deficiency, a suboptimal transplanted kidney function, and also the recipient's previous history of subtotal or incomplete parathyroidectomy. The characteristic clinical and laboratory signs of posttransplant hyperparathyroidism are bone lesions, kidney graft abnormalities, hypercalcemia, and hypophosphatemia. The diagnostic algorithm includes monitoring the markers of mineral and bone metabolism, determining the bone mineral density, and imaging of thyroid glands. Correction of post-transplant hyperparathyroidism is performed surgically or pharmacologically. The article specifies the indications to, the extent and timing of parathyroidectomy, discusses the use of native vitamin D formulations, its analogues, and calcimimetics.

Effects of nonpharmacological interventions on reducing fatigue after hematopoietic stem cell transplantation

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Hedayat Jafari

2017-01-01

Full Text Available Fatigue is one of the main complaints of patients undergoing allogeneic and autologous hematopoietic stem cell transplantation (HSCT. Since nonpharmacological interventions are cost-effective and causes fewer complications, this study aimed to review the studies performed on the effects of nonpharmacological interventions on fatigue in patients undergoing HSCT during September 2016. MEDLINE, CINAHL, Scientific Information Database, IranMedex, PubMed, ScienceDirect, Scopus, Magiran, and IRANDOC databases were searched using Persian and English keywords. A total of 1217 articles were retrieved, 21 of which were used in this study. Exercise is known as an effective intervention in alleviating physical and mental problems of patients undergoing stem cell transplant. This review-based study showed that nonpharmacological methods such as exercise might be effective in decreasing fatigue in patients undergoing stem cell transplant. There is a multitude of studies on some of the complementary and alternative therapy methods, such as music therapy, yoga, relaxation, and therapeutic massage. These studies demonstrated the positive effects of the aforementioned therapies on reduction of fatigue in patients undergoing stem cell transplantation. All the investigated methods in this study were nonaggressive, safe, and cost-effective and could be used along with common treatments or even as an alternative for pharmacological treatments for the reduction, or elimination of fatigue in patients undergoing stem cell transplantation. Given the advantages of complementary and alternative medicine, conducting further studies on this issue is recommended to reduce fatigue in patients after stem cell transplantation.

Reactivation of Cutaneous Leishmaniasis after Renal Transplantation: A Case Report

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Hossein Mortazavi

2014-01-01

Full Text Available A 45-year-old man with reactivation of previously existing and subsiding cutaneous leishmaniasis on his wrist and lower leg (shin after renal transplantation was admitted to our dermatology service on March 2008. He presented to us with two huge tumoral and cauliflower-like lesions. Skin smear and histopathology of skin showed leishman bodies and confirmed the diagnosis. After renal transplantation, he received cyclosporine plus prednisolone to induce immunosuppression and reduce the probability of transplant rejection. After immunosuppressive therapy, reactivation of cutaneous leishmaniasis with the above presentation took place. The patient responded to 800 mg/day intravenous sodium stibogluconate for 3 weeks plus local cryotherapy. Systemic plus local therapy along with reducing the doses of immunosuppressive drugs led to improvement of lesions. Reactivation of leishmaniasis after immunosuppression has been rarely reported.

Pre-Liver Transplant: Tips Versus Distal Splenorenal Shunt

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Thomas W. Faust

1997-01-01

Full Text Available Recurrent variceal bleeding in liver transplant candidates with end-stage liver disease can complicate or even prohibit a subsequent transplant procedure (OLT. Endoscopic sclero-therapy and medical therapy are considered as first-line management with surgical shunts reserved for refractory situations. Surgical shunts can be associated with a high mortality in this population and may complicate subsequent OLT. The transjugular intrahepatic portosystemic shunt (TIPS has been recommended in these patients as a bridge to OLT. This is a new modality that has not been compared with previously established therapies such as the distal splenorenal shunt (DSRS. In this study we report our experience with 35 liver transplant recipients who had a previous TIPS (18 patients or DSRS (17 patients for variceal bleeding. The TIPS group had a significantly larger proportion of critically ill and Child-Pugh C patients. Mean operating time was more prolonged in the DSRS group (P=0.014 but transfusion requirements were similar. Intraoperative portal vein blood flow measurements averaged 2132±725 ml/min in the TIPS group compared with 1120±351ml/min in the DSRS group (P<0.001. Arterial flows were similar. Mean ICU and hospital stays were similar. There were 3 hospital mortalities in the DSRS group and none in the TIPS group (P=0.1. We conclude that TIPS is a valuable tool in the management of recurrent variceal bleeding prior to liver transplantation. Intra0Perative hemodynamic measurements suggest a theoretical advantage with TIPS. In a group of patients with advanced liver disease we report an outcome that is similar to patients treated with DSRS prior to liver transplantation. The role of TIPS in the treatment of nontransplant candidates remains to be clarified.

Overview of marrow transplantation

International Nuclear Information System (INIS)

Thomas, E.D.

1985-01-01

Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references

Succesful therapy of viral leukemia by transplantation of histocompatibly unmatched marrow

International Nuclear Information System (INIS)

Meredith, R.F.; OKunewick, J.P.; Kuhnert, P.M.; Brozovich, B.J.; Weaver, E.V.

1978-01-01

The therapeutic effectiveness on murine viral-leukemia of allogeneic or hybrid hematopoietic cells transplanted from leukemia-virus resistant donors was evaluated and compared with that of syngeneic cells. Transplantation of syngeneic cells gave no protection to the viral-leukemic mice. Transplantation of spleen cells from allogeneic donors resulted in early deaths of both leukemic and non-leukemic recipients. Transplantation of hybrid spleen cells resulted in no long-term survival of the leukemic mice. However, there were a number of long-term survivors among the leukemic recipients of allogeneic or hybrid marrow cells. Engraftment of allogeneic marrow resulted in a large number of survivors. Hybrid marrow recipients showed an even better survival, but some leukemia relapses. Tests of the longterm survivors revealed that even though they gave no evidence of leukemia they still harbored the active virus. This suggests that the mechanism of protection may be related to some inherent characteristic of the donor cells rendering them refractory to viral transformation. A difference in graft-versus-host (GvH) response between the leukemic and control mice was also found after transplantation of allogeneic cells. While all of the controls died of GvH reaction, none of the leukemic recipients showed severe GvH response, suggesting a possible effect of the leukemia on histocompatibility. No GvH reaction was found with hybrid marrow engraftment, although some of the leukemic recipients reconstituted with F 1 cells did die of leukemic relapse. (author)

[Rare diagnostics of infective endocarditis after kidney transplantation].

Science.gov (United States)

Dedinská, Ivana; Skalová, Petra; Mokáň, Michal; Martiaková, Katarína; Osinová, Denisa; Pindura, Miroslav; Palkoci, Blažej; Vojtko, Marián; Hubová, Janka; Kadlecová, Denisa; Lendová, Ivona; Zacharovský, Radovan; Pekar, Filip; Kaliská, Lucia

2016-01-01

Infective endocarditis in a patient after kidney transplantation is a serious infective complication which increases the risk of loss of the graft and also the mortality of patients. The most important predisposing factor is the immunosuppressive therapy - mainly induction immunosuppression.Material and case description: 250 patients underwent kidney transplantation throughout the period of 12 years in the Transplant Center Martin. This set of patients included 5 patients (2 %) after heart valve replacement. We present the case of a patient after kidney transplantation with development of endocarditis of the bioprosthesis of the aortic valve one month after successful kidney transplantation. Diagnostics of endocarditis by standard procedures (examination by transthoracic echocardiogram, transesophageal echocardiography, hemocultures) was unsuccessful. We rarely diagnosed endocarditis only by PET-CT examination with a consequent change of the antibiotic treatment and successful managing of this post-transplant complication. Endocarditis after kidney transplantation is a serious complication which significantly worsens the mortality of patients. The risk of development of infective endocarditis after transplantation is also increased by induction, mainly by antithymocyte globulin. Diagnostics only by PET-CT examination is rare; however, in this case it fundamentally changed the approach to the patient and led to a successful treatment.

Progression of hepatic aspergillosis following second renal transplantation in a patient with recurrent glomerulonephritis

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Krishan L Gupta

2012-01-01

Full Text Available Invasive aspergillosis is a serious complication in renal transplant recipients. Hepatic involvement, although seen in liver transplant recipients, has not been reported following renal transplantation. We describe here an interesting occurrence of hepatic Aspergillus infection in a renal transplant recipient. The infection responded to anti-fungal therapy, but there was re-activation following a second renal transplant. In addition, the patient had recurrence of the underlying membrano-proliferative glomerulonephritis following both transplants. The relevant existing literature relating to these problems has been reviewed.

The regulatory roles of B cell subsets in transplantation.

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Chu, Zhulang; Zou, Weilong; Xu, Yanan; Sun, Qiquan; Zhao, Yong

2018-02-01

B cells mediate allograft rejection through antigen presentation, and production of cytokines and antibodies. More and more immunosuppressive agents specifically targeting B cells and plasma cells have been applied in clinical transplantation. However, recent studies have indicated the regulatory roles of B cells. Therefore, it is vital to clarify the different effects of B cell subsets in organ transplantation so that we can completely understand the diverse functions of B cells in transplantation. Areas covered: This review focuses on the regulatory roles of B cells in transplantation. B cell subsets with immune modulation and factors mediating immunosuppressive functions of regulatory B (Breg) cells were analyzed. Therapies targeting B cells and the application of B cells for transplant tolerance induction were discussed. Expert commentary: Besides involving rejection, B cells could also play regulatory roles in transplantation. Breg cells and the related markers may be used to predict the immune tolerant state in transplant recipients. New therapeutic strategies targeting B cells should be explored to promote tolerance induction with less impact on the host's protective immunity in organ transplanted patients.

Effects of Healing Touch and Relaxation Therapy on Adult Patients Undergoing Hematopoietic Stem Cell Transplant: A Feasibility Pilot Study.

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Lu, Der-Fa; Hart, Laura K; Lutgendorf, Susan K; Oh, Hyunkyoung; Silverman, Margarida

2016-01-01

Stem cell transplant (SCT), considered the current standard of care for adults with advanced cancers, can lead to substantial deconditioning and diminished well-being. Attending to life quality of SCT recipients is now viewed as essential. The objective of this study was to identify the feasibility and preliminary efficacy of healing touch (HT) and relaxation therapy (RT) with patients undergoing SCT. A randomized prospective design compared 13 SCT patients who received HT daily while hospitalized to 13 similar SCT patients who received daily RT. The clinical outcomes of the 2 groups were also compared with retrospective clinical data of 20 patients who received SCT during the same year. The mean age of participants was 57 years, with 54% receiving autologous and 46% receiving allogeneic transplants. All patients assigned to the HT group completed the protocol. Only 60% of the relaxation group completed the intervention. Both interventions produced improvement in psychosocial measures and a shorter hospital length of stay (LOS) than the historical group. Differential results for LOS were related to the type of transplant received. The LOS differences were not statistically significant but could be clinically significant. Healing touch was a better tolerated modality by this population. Future research is needed to validate the LOS advantage of the HT and RT interventions, explore the differences in effect found with different transplant types, and identify patients who can tolerate RT. The LOS reduction could result in decreased cost. Second, mood and function improvements support quality of life during SCT treatment.

Advances in pancreatic islet transplantation for the treatment of diabetes%胰岛移植治疗糖尿病的现状和进展

Institute of Scientific and Technical Information of China (English)

彭丹凤; 贾伟平

2012-01-01

胰岛移植是治疗糖尿病尤其是1型糖尿病的一种简单有效的方法,相较与胰腺移植,它较为简单和方便,但存在组织来源匮乏和免疫移植排斥等障碍.新的胰岛分离纯化方法提高了供移植的胰岛的纯度和活性.成体干细胞研究、异种移植研究,有望解决移植的供源问题.Edmonton方案在胰岛移植的临床应用中具有里程碑意义.新型的免疫抑制剂和免疫诱导剂的研究可以提高临床胰岛移植的成功率.%Objective Pancreatic islet transplantation is effective in treating diabetes, especially in type 1 diabetes. It can provide diabetes management with good glycemic control and insulin independence. Compared to pancreas transplantation, islet transplantation is technically much simplier and safer. However, currently its clinical use is highly restricted by a series of influence factors, including lack of sufficient donor organs and the side effects of immunosuppressive therapy. With recent advances in methods of islet isolation and purification, we can get better donor organs. Deriving islet cells from other sources such as pigs, human pancreatic duct cells, fetal pancreatic stem cells, and embryonic stem cells will overcome shortage of donor organs. The use of the Edmonton protocol has been proved to be the key procedure of clinical islet transplantation. And study of new immunosuppressive drugs and immunomodulators can provide higher rate of success for clinical islet transplantation.

Solid Organ Transplantation in Patients with Inflammatory Bowel Diseases (IBD: Analysis of Transplantation Outcome and IBD Activity in a Large Single Center Cohort.

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Fabian Schnitzler

Full Text Available Currently, limited data of the outcome of inflammatory bowel disease (IBD in patients after solid organ transplantation (SOT are available. We aimed to analyze effects of SOT on the IBD course in a large IBD patient cohort.Clinical data from 1537 IBD patients were analyzed for patients who underwent SOT (n = 31 between July 2002 and May 2014. Sub-analyses included SOT outcome parameters, IBD activity before and after SOT, and efficacy of IBD treatment.4.74% of patients with ulcerative colitis (UC and 0.84% of patients with Crohn's disease (CD underwent SOT (p = 2.69 x 10(-6, UC vs. CD. 77.4% of patients with SOT underwent liver transplantation (LTx with tacrolimus-based immunosuppressive therapy after SOT. All LTx were due to primary sclerosing cholangitis (PSC or PSC overlap syndromes. Six patients (19.4% required renal transplantation and one patient (3.2% heart transplantation. A survival rate of 83.9% after a median follow-up period of 103 months was observed. Before SOT, 65.0% of patients were in clinical remission and 5 patients received immunosuppressive therapy (16.1%. After SOT, 61.0% of patients were in remission (p = 1.00 vs. before SOT and 29.0% required IBD-specific immunosuppressive or anti-TNF therapy (p = 0.54 vs. before SOT. 42.9% of patients with worsening of IBD after SOT were at higher risk of needing steroid therapy for increased IBD activity (p = 0.03; relative risk (RR: 10.29; 95% CI 1.26-84.06. Four patients (13.0% needed anti-TNF therapy after SOT (response rate 75%.SOT was more common in UC patients due to the higher prevalence of PSC-related liver cirrhosis in UC. Despite mainly tacrolimus-based immunosuppressive regimens, outcome of SOT and IBD was excellent in this cohort. In this SOT cohort, concomitant immunosuppressive therapy due to IBD was well tolerated.

Palmoplantar peeling secondary to sirolimus therapy.

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Liu, L S; McNiff, J M; Colegio, O R

2014-01-01

Sirolimus (rapamycin) is an immunosuppressive agent commonly used in transplant recipients. Although sirolimus has less renal toxicity than calcineurin inhibitors, its use has been limited by its side effects. The most common cutaneous pathologies associated with sirolimus are inflammatory acneiform eruptions, lymphedema and aphthous ulcers. We present a novel cutaneous manifestation of sirolimus therapy that limited its use in at least one transplant recipient. Upon commencing sirolimus therapy, four solid organ transplant recipients developed tender, nonpruritic palmoplantar peeling within the first month of therapy. The peeling clinically resembled a mild form of hand-foot syndrome, yet none of the patients had been treated with chemotherapeutics. Desquamation presented on the palms and soles with dry vesicles and minor peeling extending to the dorsal aspects of the hands and feet. Histologically, the lesions were noninflammatory; the epidermis showed subtle separation between keratinocytes, suggesting either spongiosis or a defect in intercellular adhesion. One patient opted to discontinue treatment because of the tenderness associated with the palmoplantar peeling, which resulted in complete resolution within 2 weeks. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Features of transfusion therapy in patients undergoing hematopoietic stem cell transplantation. Review of the literature

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D. N. Balashov

2014-07-01

Full Text Available The indications for transfusion of blood components support after stem cell transplantation (SCT usually do not differ form other clinical situations, but the rules for such therapy have a number of features. One of them is the possibility of inconsistence of AB0 group between donor and recipient of hematopoietic stem cells, which is not only fraught with the development of various alloimmune complications, but also fundamentally changes the standards for the selection of blood components for transfusion. A major problem after HSCT is a secondary immunodeficiency, which is important to consider for ensuring prevention of transfusion-transmitted infections (eg, CMV, as well as to carry out activities aimed for the prevention of transfusion- associated graft-versus-host disease. HSCT is a medical technology today, the effectiveness of which is often dependent on the accuracy and integrity of its implementation. So, serious attitude to various supportive therapy, including transfusions of blood components is an important component which determines the success of the treatment.

Features of transfusion therapy in patients undergoing hematopoietic stem cell transplantation. Review of the literature

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D. N. Balashov

2013-01-01

Full Text Available The indications for transfusion of blood components support after stem cell transplantation (SCT usually do not differ form other clinical situations, but the rules for such therapy have a number of features. One of them is the possibility of inconsistence of AB0 group between donor and recipient of hematopoietic stem cells, which is not only fraught with the development of various alloimmune complications, but also fundamentally changes the standards for the selection of blood components for transfusion. A major problem after HSCT is a secondary immunodeficiency, which is important to consider for ensuring prevention of transfusion-transmitted infections (eg, CMV, as well as to carry out activities aimed for the prevention of transfusion- associated graft-versus-host disease. HSCT is a medical technology today, the effectiveness of which is often dependent on the accuracy and integrity of its implementation. So, serious attitude to various supportive therapy, including transfusions of blood components is an important component which determines the success of the treatment.

An economic assessment of contemporary kidney transplant practice.

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Axelrod, David A; Schnitzler, Mark A; Xiao, Huiling; Irish, William; Tuttle-Newhall, Elizabeth; Chang, Su-Hsin; Kasiske, Bertram L; Alhamad, Tarek; Lentine, Krista L

2018-05-01

Kidney transplantation is the optimal therapy for end-stage renal disease, prolonging survival and reducing spending. Prior economic analyses of kidney transplantation, using Markov models, have generally assumed compatible, low-risk donors. The economic implications of transplantation with high Kidney Donor Profile Index (KDPI) deceased donors, ABO incompatible living donors, and HLA incompatible living donors have not been assessed. The costs of transplantation and dialysis were compared with the use of discrete event simulation over a 10-year period, with data from the United States Renal Data System, University HealthSystem Consortium, and literature review. Graft failure rates and expenditures were adjusted for donor characteristics. All transplantation options were associated with improved survival compared with dialysis (transplantation: 5.20-6.34 quality-adjusted life-years [QALYs] vs dialysis: 4.03 QALYs). Living donor and low-KDPI deceased donor transplantations were cost-saving compared with dialysis, while transplantations using high-KDPI deceased donor, ABO-incompatible or HLA-incompatible living donors were cost-effective (<$100 000 per QALY). Predicted costs per QALY range from $39 939 for HLA-compatible living donor transplantation to $80 486 for HLA-incompatible donors compared with $72 476 for dialysis. In conclusion, kidney transplantation is cost-effective across all donor types despite higher costs for marginal organs and innovative living donor practices. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Autogenous transplantation of maxillary and mandibular molars.

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Reich, Peter P

2008-11-01

Autogenous tooth transplantation has been used as a predictable surgical approach to correct malocclusion and replace edentulous areas. This article focuses on the surgical approach and technique for molar transplantation. Thirty-two patients aged between 11 and 25 years underwent 44 autogenous molar transplantations. The procedure involved transplantation of impacted or newly erupted third molars into the extraction sockets of nonrestorable molars and surgical removal and replacement of horizontally impacted molars into their proper vertical alignment. Five basic procedural concepts were applied: 1) atraumatic extraction, avoiding disruption of the root sheath and root buds; 2) apical contouring of bone at the transplantation site and maxillary sinus lift via the Summers osteotome technique, when indicated, for maxillary molars; 3) preparation of a 4-wall bony socket; 4) avoidance of premature occlusal interferences; and 5) stabilization of the tooth with placement of a basket suture. All 32 patients successfully underwent the planned procedure. To date, 2 patients have had localized infection that resulted in loss of the transplant. The remaining 42 transplants remain asymptomatic and functioning, with a mean follow-up period of 19 months. No infection, ankylosis, loss of the transplant, or root resorption has been noted. In addition, endodontic therapy has not been necessary on any transplanted teeth. Autogenous tooth transplantation has been discussed and described in the literature previously, with a primary focus on cuspid and bicuspid transplantation. The molar transplant is infrequently discussed in today's literature, possibly because of the preponderance of titanium dental implants. Autogenous molar transplantation is a viable procedure with low morbidity and excellent functional and esthetic outcomes. This report shows the successful transplantation of 42 of 44 molars in 32 patients with a mean follow-up period of 19 months.

Four decades of kidney transplantation in Cuba.

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Alfonzo, Jorge P

2013-01-01

This article describes the background, beginnings, development, evolution and outcomes of kidney transplantation in Cuba. Nephrology as a medical specialty in Cuba began in 1962 and was formalized in 1966. Conditions were created to implement renal replacement therapy (including transplants), bring nephrology care to the entire country and train human resources who would assume this responsibility, making Cuba one of the first countries with a comprehensive program for renal patient care. After three unsuccessful cadaveric-donor kidney transplantations in 1968-69, the ensuing history of kidney transplantation can be summarized in the following three stages. 1970-1975: In January 1970, cadaveric-donor kidney transplantation began at the Nephrology Institute. That year, 17 kidney transplantations were performed; four of these patients lived with functional kidneys for 15-25 years; 10-year graft survival was 23.5% (Kaplan-Meier survival curve); HLA typing began in 1974. By December 1975, 170 grafts had been done in three hospitals. 1976-1985: Seven transplantation centers performed 893 grafts during this period. HLA-DR typing was introduced in 1976 and the National Histocompatibility Laboratory Network was founded in 1978. The first related living-donor kidney transplantation was done in 1979. 1986-2011: The National Kidney Transplantation Coordinating Center and the National Kidney Transplantation Program were created in 1986; the first combined kidney-pancreas transplantation was performed the same year. In 1990, cyclosporine and the Cuban monoclonal antibody IOR-T3 were introduced for immunosuppression to prevent rejection, as were other Cuban products (hepatitis B vaccine and recombinant human erythropoietin) for transplant patients. By December 2011, the cumulative number of transplants was 4636 (384 from related living donors). With over 40 years of experience, kidney transplantation is now well established in Cuba; it is free and universally accessible, on the

Lung transplantation in the most critically-III: forging ahead.

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Mulvihill, Michael S; Hartwig, Matthew G; Daneshmand, Mani A

2017-09-01

Lung transplantation is the gold standard therapy for patients with end-stage lung disease. The use of the lung allocation score (LAS) has permitted improved allocation of scarce pulmonary allografts. Recently, Crawford et al. examined the experience in the United States in lung transplantation in candidates with the highest LAS, demonstrating that outcomes for candidates with the highest LAS scores have improved significantly. This editorial places these data in the broader context of thoracic transplantation, and highlights the critical need for ongoing examination of this critically-ill patient population.

Exhaled nitric oxide concentration in patients after heart transplantation.

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Nadziakiewicz, P; Knapik, P; Zakliczyński, M; Zembala, M; Urbańska, E; Pacholewicz, J

2007-11-01

Nitric oxide (NO) is present in exhaled air in humans and its level may decrease in heart diseases. In the present study we prospectively investigated how heart transplantation treated with oral immunosuppresive drugs based on ciclosporine A influences the exhaled NO concentration (exNO). The study was performed in 17 patients after heart transplantation in various time after procedure and 15 nonsmoking healthy volunteers as a control group. Patients after heart transplantation were free of clinical signs of rejection. End-tidal concentration of exNO was measured by the use of a chemiluminescence method. We found no statistically significant differences in the exNO level between patients after heart transplantation and healthy controls (6.81+/-2.70 part per billion (ppb) in the transplant group vs. 6.01+/-3.43 ppb in the control group). We conclude that heart transplantation and immunosuppresive therapy do not influence the exhaled NO concentration.

Invasive Pulmonary Aspergillosis in a Sickle Cell Patient Transplant Recipient: A Successful Treatment

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Katia Paciaroni

2015-08-01

Full Text Available Sickle Cell Anaemia (SCA is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT is the only curative approach. Nevertheless the decision to perform a marrow transplant includes the risk of major complications  and mortality transplant related. The infections represent the main cause of mortality for SCA patients undergoing transplant. Invasive Pulmonary Aspergillosis (IPA is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report,  we describe a patient with SCA who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to the surgery, despite  mild chronic GVHD and with continuing immunosuppression therapy. This case shows that IPA occurring in bone marrow recipient with SCA can be successful treated

A drive through cellular therapy for CLL in 2015: allogeneic cell transplantation and CARs.

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Mato, Anthony; Porter, David L

2015-07-23

Over the past decade the development of safer reduced-intensity conditioning regimens, expanded donor pools, advances in supportive care, and prevention/management of graft-versus-host disease have expanded stem cell transplantation (SCT) availability for chronic lymphocytic leukemia (CLL) patients. However, there are now increasingly active treatment options available for CLL patients with favorable toxicity profiles and convenient administration schedules. This raises the critical issue of whether or not attainment of cure remains a necessary goal. It is now less clear that treatment with curative intention and with significant toxicity is required for long-term survival in CLL. In addition, the demonstrated safety and activity of genetically modified chimeric antigen receptor (CAR) T cells present the opportunity of harnessing the power of the immune system to kill CLL cells without the need for SCT. We attempt to define the role of SCT in the era of targeted therapies and discuss questions that remain to be answered. Furthermore, we highlight the potential for exciting new cellular therapy using genetically modified anti-CD19 CAR T cells and discuss its potential to alter treatment paradigms for CLL. © 2015 by The American Society of Hematology.

BONE MINERAL DENSITY AFTER LIVER TRANSPLANTATION

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V. P. Buzulina

2010-01-01

Full Text Available Bone mineral density (BMD was estimated twice in 18 recipents of ortotopic liver transplantation. There was decreased BMD in axial so as in peripheral skeleton in early time and in vertebral or hip Ward triangle in late time following transplantation being lower in primary biliary cirrosis then in cirrosis following chronic virus hepatitis despite tacrolimus immunosupression without prednisolon. Tacrolimus immunosupression with prednisolon in primary biliary cirrosis patients in late postoperative time was associated with hard BMD lowering which correlated with glucocorticoid therapy duration and prednisolon cumulative dosis. 

ACUTE APENDICITIS IN LIVER TRANSPLANT RECIPIENTS.

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Fonseca-Neto, Olival Cirilo Lucena da; Lima, Heloise Caroline de Souza; Melo, Paulo Sérgio Vieira de; Lemos, Roberto; Leitão, Laércio; Amorim, Américo Gusmão; Lacerda, Cláudio Moura

2016-03-01

Appendicitis is a common cause of emergency surgery that in the population undergoing organ transplantation presents a rare incidence due to late diagnosis and treatment. To report the occurrence of acute appendicitis in a cohort of liver transplant recipients. Retrospective analysis in a period of 12 years among 925 liver transplants, in witch five cases of acute appendicitis were encountered. Appendicitis occurred between three and 46 months after liver transplantation. The age ranged between 15 and 58 years. There were three men and two women. The clinical presentations varied, but not discordant from those found in non-transplanted patients. Pain was a symptom found in all patients, in two cases well located in the right iliac fossa (40%). Two patients had symptoms characteristic of peritoneal irritation (40%) and one patient had abdominal distention (20%). All patients were submitted to laparotomies. In 20% there were no complications. In 80% was performed appendectomy complicated by suppuration (40%) or perforation (40%). Superficial infection of the surgical site occurred in two patients, requiring clinical management. The hospital stay ranged from 48 h to 45 days. Acute appendicitis after liver transplantation is a rare event being associated with a high rate of drilling, due to delays in diagnosis and therapy, and an increase in hospital stay.

A highly efficient method for generation of therapeutic quality human pluripotent stem cells by using naive induced pluripotent stem cells nucleus for nuclear transfer

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Sanal, Madhusudana Girija

2014-01-01

Even after several years since the discovery of human embryonic stem cells and induced pluripotent stem cells (iPSC), we are still unable to make any significant therapeutic benefits out of them such as cell therapy or generation of organs for transplantation. Recent success in somatic cell nuclear transfer (SCNT) made it possible to generate diploid embryonic stem cells, which opens up the way to make high-quality pluripotent stem cells. However, the process is highly inefficient and hence e...

Concurrent validity of kidney transplant questionnaire in US renal transplant recipients

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Chisholm-Burns MA

2011-10-01

Full Text Available Marie A Chisholm-Burns1,2, Steven R Erickson3, Christina A Spivey1, Rainer WG Gruessner2, Bruce Kaplan4 1Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy, Tucson, AZ; 2Department of Surgery, University of Arizona College of Medicine, Tucson, AZ; 3Department of Clinical Sciences, University of Michigan College of Pharmacy, Ann Arbor, MI; 4Department of Medicine, The University of Arizona College of Medicine Tucson, AZ, USA Background: Valid instrumentation in the assessment of health-related quality of life (HQoL in renal transplant recipients is critical to identifying particular nuances and determinants of HQoL in this population. Therefore, the validity of disease-specific instruments to measure HQoL in renal transplant recipients, such as the Kidney Transplant Questionnaire (KTQ, needs further investigation. The objective of this study was to assess the concurrent validity of the KTQ in adult US renal transplant recipients using the well established SF-12 Health Survey version 2 (SF-12v2 as the comparison instrument. Methods: One hundred and fourteen renal transplant recipients met the following inclusion criteria for this study, ie, were at least 21 years of age, more than two years post-transplant, and receiving immunosuppressant therapy. Subjects were asked to complete a series of HQoL instruments, ie, the KTQ and the SF-12v2 (physical component summary [PCS-12] and mental component summary [MCS-12]. Descriptive statistics were calculated, and correlational analyses were conducted to examine the concurrent validity of the HQoL instruments. Results: Among 100 participants (87.7% response rate, the majority of participants were male (52%, had deceased donor transplants (63%, and received Medicare benefits (84%. PCS-12 was positively correlated with three of five KTQ subscales (P < 0.05, ie, KTQ-physical (r = 0.43, KTQ-fatigue (r = 0.42, and KTQ-uncertainty/fear (r = 0.2. MCS-12 was positively correlated

[Sirolimus associated pneumonitis in a hematopoietic stem cell transplant patient].

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García, Estefanía; Buenasmañanas, Diana; Martín, Carmen; Rojas, Rafael

2015-07-06

Sirolimus (SR) is a lipophilic macrocytic lactone with immunosuppressive properties (mTOR inhibitor) commonly used in solid organ transplantation and recently introduced in the prophylaxis and treatment of graft-versus-host disease. Its numerous side effects include: hyperlipidemia, arthralgias, noncardiac peripheral edema, thrombotic microangiopathy and interstitial pneumonitis. SR-associated pneumonitis is a rare but potentially serious complication due to its increasing utilization in transplant patients. We report the case of a patient undergoing hematopoietic stem cell transplantation with severe respiratory distress and SR therapy. Microbiological tests were all negative and other complications related to transplantation were discarded. The chest computed tomography of high-resolution showed pneumonitis. The SR therapy was interrupted and treatment was started with steroids with resolution of symptoms. SR associated pneumonitis is a potentially fatal side effect. In patients treated with SR and respiratory failure, we must suspect this complication because early recognition along with drug discontinuation and steroid treatment is essential to reverse this complication. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Recurrence of lymphangioleiomyomatosis: Nine years after a bilateral lung transplantation.

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Zaki, Khawaja S; Aryan, Zahra; Mehta, Atul C; Akindipe, Olufemi; Budev, Marie

2016-03-24

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive lethal lung disease primary afflicting young women. LAM is characterized by proliferation of abnormal smooth muscle cells that target the lungs, causing cystic destruction and eventual respiratory failure leading to death. Recent ten year mortality due to end stage LAM has been reported to be approximately 10%-20%, but may vary. The decline in lung function in LAM is gradual, occurring at a rate of about 3% to 15% per year but can vary from patient to patient. But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Lung transplantation is a viable option for patients who continue to have decline in lung function despite mTOR therapy. Unique issues that may occur post-transplant in a recipient with LAM include development of chylous effusion and a risk of recurrence. We describe a case of LAM recurrence in a bilateral lung transplant recipient who developed histological findings of LAM nine years after transplantation.

The Results of Fetal Chondrocytes Transplantation in Patients with Rheumatoid Arthritis

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Natalya Krivoruchko

2014-12-01

Full Text Available Introduction. Nowadays anti-inflammatory and immunosuppressive therapy has significantly improved the quality of life and prognosis of rheumatoid arthritis (RA. Nevertheless, there are still many patients with progressive rheumatoid inflammation, resulting in the destruction of joints. Cell therapy seems like a promising direction in rheumatology. The aim of our research was to evaluate the efficacy of fetal chondrocyte transplantation in patients with RA.Methods. We examined 60 patients with rheumatoid arthritis (I - III stages between 20 and 63 years of age. They were divided into 2 groups: the first group underwent the fetal chondrocytes transplantation (n = 40, and the second was a control group who got conservative therapy (n = 20. Donor cells were taken from the chondrogenic layer of the humerus or femur heads and hip condyles of human embryos in gestation for 17-20 weeks. A suspension of fetal chondrocytes injected into affected areas of the articular surfaces under X-ray control. Cell viability was determined before the injection. Efficacy of the therapy was assessed by clinical, instrumental, and laboratory tests. This clinical trial was allowed by The Ministry of Public Health and Ethics Committee. All of our patients gave informed consent for the fetal chondrocytes transplantation.Results. Evaluation of the clinical manifestations of RA in the first group of patients showed 3.7 times decrease in pain and 1.6 times relief of synovitis. Complete reduction of contracture was observed in 82% of patients in the first group. Morphometric changes in X-ray demonstrated inhibition of the destruction in articular cartilage and surfaces of bones after transplantation of fetal chondrocytes. The dynamics of morphological changes in synovium showed 2.5 times reduction of the inflammatory reaction. Transplantation of fetal chondrocytes led to a significant reduction in ESR, CRP, fibrinogen , γ-globulin after a period of 12 months (p < 0

New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

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Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

2015-08-01

A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

Transplanted Human Stem Cell-Derived Interneuron Precursors Mitigate Mouse Bladder Dysfunction and Central Neuropathic Pain after Spinal Cord Injury.

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Fandel, Thomas M; Trivedi, Alpa; Nicholas, Cory R; Zhang, Haoqian; Chen, Jiadong; Martinez, Aida F; Noble-Haeusslein, Linda J; Kriegstein, Arnold R

2016-10-06

Neuropathic pain and bladder dysfunction represent significant quality-of-life issues for many spinal cord injury patients. Loss of GABAergic tone in the injured spinal cord may contribute to the emergence of these symptoms. Previous studies have shown that transplantation of rodent inhibitory interneuron precursors from the medial ganglionic eminence (MGE) enhances GABAergic signaling in the brain and spinal cord. Here we look at whether transplanted MGE-like cells derived from human embryonic stem cells (hESC-MGEs) can mitigate the pathological effects of spinal cord injury. We find that 6 months after transplantation into injured mouse spinal cords, hESC-MGEs differentiate into GABAergic neuron subtypes and receive synaptic inputs, suggesting functional integration into host spinal cord. Moreover, the transplanted animals show improved bladder function and mitigation of pain-related symptoms. Our results therefore suggest that this approach may be a valuable strategy for ameliorating the adverse effects of spinal cord injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of post-transplantation lymphoproliferative disorders after kidney transplant with rituximab and conversion to m-TOR inhibitor.

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Nieto-Rios, John Fredy; Gómez de Los Ríos, Sandra Milena; Serna-Higuita, Lina María; Ocampo-Kohn, Catalina; Aristizabal-Alzate, Arbey; Gálvez-Cárdenas, Kenny Mauricio; Zuluaga-Valencia, Gustavo Adolfo

2016-12-30

Post-transplantation lymphoproliferative disorders are serious complications of organ transplantation which treatment is not yet standardized. To describe the clinical response, overall and graft survival of patients in our center with this complication after kidney transplantation, which received rituximab as part of their treatment as well as conversion to m-TOR. Retrospective study, which included patients, diagnosed with post-transplant lymphoproliferative disorders after kidney transplantation from January 2011 to July 2014. Eight cases were found with a wide spectrum of clinical presentations. Most had monomorphic histology, 85% were associated with Epstein-Barr virus, 25% of patients had tumor involvement of the renal graft, and 12.5% ​​had primary central nervous system lymphoma. All patients were managed with reduction of immunosuppression, conversion to m-TOR (except one who lost the graft at diagnosis) and rituximab-based therapy. The overall response rate was 87.5% (62.5% complete response, 25% partial response). Survival was 87.5% with a median follow-up of 34 months. An additional patient lost the graft, with chronic nephropathy already known. All the remaining patients had stable renal function. There are no standardized treatment regimens for lymphoproliferative disorders after kidney transplantation, but these patients can be managed successfully with reduction of immunosuppression, conversion to m-TOR and rituximab-based schemes.