Browsing by Subject "transplantation"

Now showing 1 - 10 of 10
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    Current Status of Cord Blood Banking and Transplantation in the United States and Europe
    (Elsevier, 2001-12-01) Ballen, Karen; Broxmeyer, Hal E.; McCullough, Jeffrey; Piaciabello, Wanda; Rebulla, Paolo; Verfaillie, Catherine M.; Wagner, John E.; Microbiology and Immunology, School of Medicine
    Cord blood (CB) transplantation has expanded the ability of the transplantation community to meet the growing needs of their patients. Clinical data over the last decade show promising results in CB transplantation using blood from related as well as unrelated donors. Basic science continues to look for ways to expand the quality and quantity of CB. CB banks are now established around the world, with major efforts to standardize banking to facilitate regulation, collection, processing, and distribution as a way of providing the highest-quality CB for patient use. This review article discusses the current status of CB transplantation and banking in the United States and Europe.
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    Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: A multicenter study
    (Wiley Online Library, 2016-04) Mueller, Jessica L.; King, Linsday Y.; Johnson, Kara B.; Gao, Tian; Nephew, Lauren D.; Kothari, Darshan; Simpson, Mary Ann; Zheng, Hui; Wei, Lan; Corey, Kathleen E.; Misdraji, Joseph; Lee, Joon Hyoek; Lin, M. Valerie; Gogela, Neliswa A.; Fuchs, Bryan C.; Tanabe, Kenneth K.; Gordon, Fredric D.; Curry, Michael P.; Chung, Raymond T.
    Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93–4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non-CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.
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    Mesenteric lymph nodes as alternative site for pancreatic islet transplantation in a diabetic rat model
    (BMC, 2019-04) Veroux, Massimiliano; Bottino, Rita; Santini, Roberta; Bertera, Suzanne; Corona, Daniela; Zerbo, Domenico; Volti, Giovanni Li; Ekser, Burcin; Puzzo, Lidia; Raffaele, Marco; Bianco, Salvatore Lo; Giaquinta, Alessia; Veroux, Pierfrancesco; Vanella, Luca; Surgery, School of Medicine
    Background Islet transplantation has progressively become a safe alternative to pancreas transplantation for the treatment of type 1 diabetes. However, the long-term results of islet transplantation could be significantly increased by improving the quality of the islet isolation technique even exploring alternative islet transplantation sites to reduce the number of islets required to mitigate hyperglycemia. The goal of the study was to test the lymph node as a suitable anatomical location for islet engraftment in a rodent model. Methods Forty Lewis rats, 6–8 weeks old, body weight 250–300 g, have been used as islet donors and recipients in syngeneic islet transplantation experiments. Ten rats were rendered diabetic by one injection of 65 mg/Kg of streptozotocin. After pancreas retrieval from non diabetic donors, islet were isolated and transplanted in the mesenteric lymph nodes of 7 diabetic rats. Rats were followed for 30 days after islet transplantation. Results A total of 7 islet transplantations in mesenteric lymph nodes have been performed. Two rats died 24 and 36 h after transplantation due to complications. No transplanted rat acquired normal glucose blood levels and insulin independence after the transplantation. However, the mean blood levels of glycemia were significantly lower in transplanted rats compared with diabetic rats (470.4 mg/dl vs 605 mg/dl, p 0.04). Interestingly, transplanted rats have a significant weight increase after transplantation compared to diabetic rats (mean value 295 g in transplanted rats vs 245 g in diabetic rats, p < 0.05), with an overall improvement of social activities and health. Immunohistochemical analysis of the 5 mesenteric lymph nodes of transplanted rats demonstrated the presence of living islets in one lymph node. Conclusions Although islet engraftment in lymph nodes is possible, islet transplantation in lymph nodes in rats resulted in few improvements of glucose parameters.
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    Prostaglandin E2 Enhances Aged Hematopoietic Stem Cell Function
    (Springer, 2021-10) Patterson, Andrea M.; Plett, P. Artur; Sampson, Carol H.; Simpson, Edward; Liu, Yunlong; Pelus, Louis M.; Orschell, Christie M.; Medicine, School of Medicine
    Aging of hematopoiesis is associated with increased frequency and clonality of hematopoietic stem cells (HSCs), along with functional compromise and myeloid bias, with donor age being a significant variable in survival after HSC transplantation. No clinical methods currently exist to enhance aged HSC function, and little is known regarding how aging affects molecular responses of HSCs to biological stimuli. Exposure of HSCs from young fish, mice, nonhuman primates, and humans to 16,16-dimethyl prostaglandin E2 (dmPGE2) enhances transplantation, but the effect of dmPGE2 on aged HSCs is unknown. Here we show that ex vivo pulse of bone marrow cells from young adult (3 mo) and aged (25 mo) mice with dmPGE2 prior to serial competitive transplantation significantly enhanced long-term repopulation from aged grafts in primary and secondary transplantation (27 % increase in chimerism) to a similar degree as young grafts (21 % increase in chimerism; both p < 0.05). RNA sequencing of phenotypically-isolated HSCs indicated that the molecular responses to dmPGE2 are similar in young and old, including CREB1 activation and increased cell survival and homeostasis. Common genes within these pathways identified likely key mediators of HSC enhancement by dmPGE2 and age-related signaling differences. HSC expression of the PGE2 receptor EP4, implicated in HSC function, increased with age in both mRNA and surface protein. This work suggests that aging does not alter the major dmPGE2 response pathways in HSCs which mediate enhancement of both young and old HSC function, with significant implications for expanding the therapeutic potential of elderly HSC transplantation.
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    Pulmonary Retention of Adipose Stromal Cells Following Intravenous Delivery Is Markedly Altered in the Presence of ARDS
    (2016) Lu, Hongyan; Cook, Todd; Poirier, Christophe; Merfeld-Clauss, Stephanie; Petrache, Irina; March, Keith L.; Bogatcheva, Natalia V.; Department of Medicine, IU School of Medicine
    Transplantation of mesenchymal stromal cells (MSCs) has been shown to effectively prevent lung injury in several preclinical models of acute respiratory distress syndrome (ARDS). Since MSC therapy is tested in clinical trials for ARDS, there is an increased need to define the dynamics of cell trafficking and organ-specific accumulation. We examined how the presence of ARDS changes retention and organ-specific distribution of intravenously delivered MSCs isolated from subcutaneous adipose tissue [adipose-derived stem cells (ADSCs)]. This type of cell therapy was previously shown to ameliorate ARDS pathology. ARDS was triggered by lipopolysaccharide (LPS) aspiration, 4 h after which 300,000 murine CRE+ ADSCs were delivered intravenously. The distribution of ADSCs in the lungs and other organs was assessed by real-time polymerase chain reaction (PCR) of genomic DNA. As anticipated, the majority of delivered ADSCs accumulated in the lungs of both control and LPS-challenged mice, with minor amounts distributed to the liver, kidney, spleen, heart, and brain. Interestingly, within 2 h following ADSC administration, LPS-challenged lungs retained significantly lower levels of ADSCs compared to control lungs (∼7% vs. 15% of the original dose, respectively), whereas the liver, kidney, spleen, and brain of ARDS-affected animals retained significantly higher numbers of ADSCs compared to control animals. In contrast, 48 h later, only LPS-challenged lungs continued to retain ADSCs (∼3% of the original dose), whereas the lungs of control animals and nonpulmonary organs in either control or ARDS mice had no detectable levels of ADSCs. Our data suggest that the pulmonary microenvironment during ARDS may lessen the pulmonary capillary occlusion by MSCs immediately following cell delivery while facilitating pulmonary retention of the cells.
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    Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
    (SAGE, 2020-07-14) Zhou, Zheng; Nath, Rajneesh; Cerny, Jan; Wang, Hai-Lin; Zhang, Mei-Jie; Abdel-Azim, Hisham; Agrawal, Vaibhav; Ahmed, Gulrayz; Al-Homsi, A. Samer; Aljurf, Mahmoud; Alkhateeb, Hassan B.; Assal, Amer; Bacher, Ulrike; Bajel, Ashish; Bashir, Qaiser; Battiwalla, Minocher; Bhatt, Vijaya Raj; Byrne, Michael; Cahn, Jean-Yves; Cairo, Mitchell; Choe, Hannah; Copelan, Edward; Cutler, Corey; Damlaj, Moussab B.; DeFilipp, Zachariah; De Lima, Marcos; Diaz, Miguel Angel; Farhadfar, Nosha; Foran, James; Freytes, César O.; Gerds, Aaron T.; Gergis, Usama; Grunwald, Michael R.; Gul, Zartash; Hamadani, Mehdi; Hashmi, Shahrukh; Hertzberg, Mark; Hildebrandt, Gerhard C.; Hossain, Nasheed; Inamoto, Yoshihiro; Isola, Luis; Jain, Tania; Kamble, Rammurti T.; Khan, Muhammad Waqas; Kharfan-Dabaja, Mohamed A.; Kebriaei, Partow; Kekre, Natasha; Khera, Nandita; Lazarus, Hillard M.; Liesveld, Jane L.; Litzow, Mark; Liu, Hongtao; Marks, David I.; Martino, Rodrigo; Mathews, Vikram; Mishra, Asmita; Murthy, Hemant S.; Nagler, Arnon; Nakamura, Ryotaro; Nathan, Sunita; Nishihori, Taiga; Olin, Rebecca; Olsson, Richard F.; Palmisiano, Neil; Patel, Sagar S.; Patnaik, Mrinal M.; Pawarode, Attaphol; Perales, Miguel-Angel; Politikos, Ioannis; Popat, Uday; Rizzieri, David; Sandmaier, Brenda M.; Savani, Bipin N.; Seo, Sachiko; Shah, Nirav N.; Uy, Geoffrey L.; Valcárcel, David; Verdonck, Leo F.; Waller, Edmund K.; Wang, Youjin; Weisdorf, Daniel; Wirk, Baldeep; Wong, Eric; Yared, Jean A.; Saber, Wael; Medicine, School of Medicine
    There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
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    Vascular and Cardiac Adult Stem Cell Therapy Center
    (Office of the Vice Chancellor for Research, 2010-04-09) March, Keith; Murphy, Michael; Petrache, Irina; Evans-Molina, Carmella; Farag, Sherif; Traktuev, Dmitry; Saadatzadeh, Reza; Johnstone, Brian; Schweitzer, Kelly; Rosen, Elliot; Chen, Peng-Sheng
    The mission of the Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST) is the discovery and clinical translation of therapies involving transplantation of adult stem cells into patients with debilitating diseases. To accomplish this, VC-CAST fosters multidisciplinary research collaborations that address both biology of adult stem cells that are readily available, and the translation of their study from the laboratory into clinical trials. The use of such cells is highly feasible, and not ethically controversial, as they are derived from readily-available tissues such as fat and bone marrow. Since its inception, VC-CAST projects have been multidisciplinary, involving multiple clinical as well as basic departments of the School of Medicine. VC-CAST projects are also collaborative, with most of the projects having one or more industrial partners. A key partnership has also been established by the creation of the Veterans Affairs Center for Regenerative Medicine (VACRM) at the Roudebush VA Medical Center in Indianapolis, which will provide a unique referral site focusing on research and implementation of first-in-human trials in the fields of poor circulation, arthritis, wound healing, diabetes, and emphysema. Given the focus of VC-CAST researchers on translation, the center is active in pursuit of intellectual property that is critical to building corporate engagement and thus the enablement of translation to clinical trials. Signature center funding has allowed IUPUI investigators to try high-risk, high-reward ideas, which could not otherwise be funded readily, via either NIH or venture-capital methods. Most of these experiments are still ongoing, but have already led to discoveries of potentially critical significance to patients. The novelty of some of these discoveries promises to attract new funding, as well as to provide bases for potential licensing revenues and startup opportunities. This poster will highlight several of these projects, representative of center activities in their collaborative, multidisciplinary and translational and potentially commercializable aspects. Some key projects are as follows: • Based on recent completion of the Phase I/II clinical trial, “Stem cell Angiogenesis to promote limb salVagE (SAVE), a new randomized Phase III clinical trial testing the use of one’s own bone marrow-derived stem cells to save legs from amputation has been initiated, with Dr. Murphy as the national PI. • Adipose Stem Cells for Peripheral Arterial Disease. • Endometrial Regenerative Cells for Peripheral Arterial Disease. • Adipose Stem Cells for treatment of Heart Attack and prevention of Heart Failure. • Adipose Stem Cells for Emphysema and other Lung Diseases • Adipose Stem Cells for Prevention and Treatment of Diabetes • Isolation and Characterization of Endothelial and Mesenchymal Stem Cells from Term Human Placenta. • Isolation and Characterization of Endothelial Colony Forming Cells (ECFCs) from Human Adult Blood Vessels
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    Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST)
    (Office of the Vice Chancellor for Research, 2011-04-08) March, Keith; Murphy, Michael; Petrache, Irina; Evans-Molina, Carmella; Traktuev, Dmitry; Johnstone, Brian; Clauss, Matthias; Hong, Soonjun; Gangaraju, Rajashekhar; Saadatzadeh, M. Reza; Schweitzer, Kelly; Rosen, Elliot; Farag, Sherif; Du, Yansheng; Chen, Peng-Sheng
    The mission of the Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST) is the discovery and clinical translation of therapies involving transplantation of adult stem cells into patients with debilitating diseases. VC-CAST fosters multidisciplinary research collaborations that address the biology of adult stem cells that are readily available, as well as the translation of their study from the laboratory into clinical trials. The use of such cells is highly feasible, and not ethically controversial, as they are derived from readily-available tissues such as fat and bone marrow. VC-CAST projects involve partners from multiple clinical and basic departments of the School of Medicine. VC-CAST projects are also collaborative externally, with most projects having one or more industrial or academic external partners. A key partnership has also been established at the Roudebush VA Medical Center in Indianapolis by creation of the Veterans Affairs Center for Regenerative Medicine (VACRM), which will provide a unique referral site focusing on research and implementation of first-in-human trials in the fields of poor circulation, stroke, arthritis, wound healing, diabetes, and emphysema. Given the focus on translation, the center is active in pursuit of intellectual property that is critical to building corporate engagement and thus the enablement of translation to clinical trials. Signature Center funding has allowed IUPUI investigators to try high-risk, high-reward ideas, which could not otherwise be funded readily, via either NIH or venture-capital methods. Most of these experiments have already led to discoveries of potentially critical significance to patients. The novelty of some of these discoveries has attracted new funding, as well as provided bases for potential licensing revenues and startup opportunities. This poster will highlight several such projects, representative of center activities in their multidisciplinary, translational, and potentially commercializable aspects. Several key projects are as follows: • Saving Legs from Amputation o Bone Marrow Stem Cells: Based on our completion of the Phase I/II clinical trial, “Stem cell Angiogenesis to promote limb salVagE (SAVE), we have initiated a randomized Phase III clinical trial testing one’s own bone marrow-derived stem cells to save legs from amputation, with Dr. Murphy as national PI. o Fat-derived (Adipose) Stem Cells– we are testing the hypothesis that these are more potent than Bone Marrow-derived stem cells with new funding from a corporate partner as well as the Department of Defense. o Endometrial Regenerative Cells– further extending above efforts, with new NIH funding to study this allogeneic (non-self, “off-the-shelf”) cell type. • Treatment of Heart Attack and prevention of Heart Failure. New data this year shows Adipose Stem Cells protect from heart damage when given systemically. • Treatment of Emphysema and other Lung Diseases. Adipose Stem Cells markedly protect from cigarette smoke-induced emphysema, a generally untreatable condition. • Prevention and Treatment of Diabetes– Adipose Stem Cells can ameliorate diabetes. This work has attracted new Veterans Affairs funding this past year. • Treatment of Parkinson’s Disease by rescue of dopaminergic neurons from death. New funding attracted in the past year by the Signature Center led to preclinical data that extended prior work in stroke models to models of Parkinson’s Disease. These data suggest that the conditioned medium from ASCs can be useful in this debilitating condition, and form the basis for a new NIH application. • Treatment of Diabetic Retinopathy by vascular stabilization using adipose stem cells. This is a new project in the past year, and has generated encouraging early data which is being used in seeking further (external) funding. • Human Placenta as a stem cell source: Isolation and Characterization of Endothelial and Mesenchymal Stem Cells from Term Placenta. • Human Saphenous Vein as a cell source: Isolation and Characterization of Endothelial Colony Forming Cells (ECFCs) from Human Saphenous Vein can form the basis for vascular network formation.
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    Voriconazole exposure and risk of cutaneous squamous cell carcinoma among lung or hematopoietic cell transplant patients: A systematic review and meta-analysis
    (Elsevier, 2019-02) Tang, Huilin; Shi, Weilong; Song, Yiqing; Han, Jiali; Epidemiology, School of Public Health
    Background Current evidence about the association between voriconazole and risk of cutaneous squamous cell carcinoma (SCC) remains inconsistent. Objective To assess the association between voriconazole use and risk of SCC. Methods We systematically searched PubMed and Embase and performed a random effects model meta-analysis to calculate the pooled relative risk (RR) with a 95% confidence interval (CI). Results Of the 8 studies involving a total of 3710 individuals with a lung transplant or hematopoietic cell transplant that were included in the qualitative analysis, 5 were included in the meta-analysis. Use of voriconazole was significantly associated with increased risk of SCC (RR, 1.86; 95% CI, 1.36-2.55). The increased risk did not differ according to type of transplantation or adjustment for sun exposure. Longer duration of voriconazole use was found to be positively associated with risk of SCC (RR, 1.72; 95% CI, 1.09-2.72). Voriconazole use was not associated with increased risk of basal cell carcinoma (RR, 0.84; 95% CI, 0.41-1.71). Limitations There were some heterogeneities in the retrospective observational studies. Conclusions Our findings support an increased risk of SCC associated with voriconazole in individuals with a lung transplant or hematopoietic cell transplant. Routine dermatologic surveillance should be performed, especially among individuals at high risk of developing SCC.
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    What Is Hot and New in Basic Science in Liver Transplantation in 2018? Report of the Basic Science Committee of the International Liver Transplantation Society
    (Wolters Kluwer, 2019-04) Martins, Paulo N.; Selzner, Markus; Dayangac, Murat; Ling, Qi; Ng, Kevin T.; Huang, Kuang-Tzu; Taner, Timucin; Mas, Valeria R.; Ekser, Burcin; Surgery, School of Medicine