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In utero transplantation

Joseph W Jackson, Trevor J Hancock, Pranay Dogra, Ravi Patel, Ravit Arav-Boger, Angela D Williams, Stephen J Kennel, Jonathan S Wall, Tim E Sparer
Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that can cause severe disease following in utero exposure, during primary infection, or latent virus reactivation in immunocompromised populations. These complications lead to a 1- to 2-billion-dollar economic burden, making vaccine development and/or alternative treatments a high priority. Current treatments for HCMV include nucleoside analogues such as ganciclovir (GCV), foscarnet, and cidofovir. Recently, letermovir, a terminase complex inhibitor, was approved for prophylaxis after stem cell transplantation...
February 13, 2019: MSphere
Adam L Vanarsdall, Andrea L Chin, Jing Liu, Theodore S Jardetzky, James O Mudd, Susan L Orloff, Daniel Streblow, Marisa M Mussi-Pinhata, Aparecida Y Yamamoto, Geraldo Duarte, William J Britt, David C Johnson
Human cytomegalovirus (HCMV) causes substantial disease in transplant patients and harms the development of the nervous system in babies infected in utero. Thus, there is a major focus on developing safe and effective HCMV vaccines. Evidence has been presented that a major target of neutralizing antibodies (NAbs) is the HCMV pentamer glycoprotein gH/gL/UL128-131. In some studies, most of the NAbs in animal or human sera were found to recognize the pentamer, which mediates HCMV entry into endothelial and epithelial cells...
February 7, 2019: Proceedings of the National Academy of Sciences of the United States of America
Angelika L Erwin, Robert J Desnick
Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by photosensitivity and by hematologic abnormalities in affected individuals. CEP is caused by mutations in the uroporphyrinogen synthase (UROS) gene. In three reported cases, CEP has been associated with a specific X-linked GATA1 mutation. Disease-causing mutations in either gene result in absent or markedly reduced UROS enzymatic activity. This in turn leads to the accumulation of the non-physiologic and photoreactive porphyrinogens, uroporphyrinogen I and coproporphyrinogen I, which damage erythrocytes and elicit a phototoxic reaction upon light exposure...
December 27, 2018: Molecular Genetics and Metabolism
Alessandra Magnani, Jean-Marie Jouannic, Jérémie Rosain, Aurélie Gabrion, Fabien Touzot, Cécile Roudaut, Sven Kracker, Nizar Mahlaoui, Antoine Toubert, Emmanuel Clave, Elisabeth A Macintyre, Isabelle Radford-Weiss, Marion Alcantara, Elisa Magrin, Brigitte Ternaux, Jennifer Nisoy, Laure Caccavelli, Anne-Marie Darras, Capucine Picard, Stéphane Blanche, Marina Cavazzana
No abstract text is available yet for this article.
February 12, 2019: Blood Advances
Shailesh Puntambekar, Seema Puntambekar, Milind Telang, Pankaj Kulkarni, Shardul Date, Mangesh Panse, Ravindra Sathe, Nikhil Agarkhedkar, Neeta Warty, Sandesh Kade, Manoj Manchekar, Mihir Chitale, Hirav Parekh, Kajal Parikh, Mehul Mehta, Bhushan Kinholkar, Joy Shankar Jana, Avinash Pare, Shailendra Kanade, Abhay Sadre, Shirish Hardikar, Advait Jathar, Tejashree Bakre, Meenakshi Chate, Raviraj Tiruke
STUDY OBJECTIVE: To evaluate 2 cases of uterine transplant surgery that used utero-ovarian veins as outflow channels, internal iliac arteries for perfusion, and the organ harvest surgery performed laparoscopically. DESIGN: Case study (Canadian Task Force Classification III). SETTING: An urban, private, tertiary care hospital. PATIENTS: Two patients, ages 30 and 24 years, diagnosed with absolute uterine factor infertility secondary to Mayer-Rokitansky-Küster-Hauser syndrome underwent related living donor uterine transplants; donors were their mothers with normal menses...
December 29, 2018: Journal of Minimally Invasive Gynecology
Nicholas J Ahn, John D Stratigis, Barbara E Coons, Alan W Flake, Hyun-Duck Nah-Cederquist, William H Peranteau
In utero transplantation (IUT) is a unique and versatile mode of therapy that can be used to introduce stem cells, viral vectors, or any other substances early in the gestation. The rationale behind IUT for therapeutic purposes is based on the small size of the fetus, the fetal immunologic immaturity, the accessibility and proliferative nature of the fetal stem or progenitor cells, and the potential to treat a disease or the onset of symptoms prior to birth. Taking advantage of these normal developmental properties of the fetus, the delivery of hematopoietic stem cells (HSC) via an IUT has the potential to treat congenital hematologic disorders such as sickle cell disease, without the required myeloablative or immunosuppressive conditioning required for postnatal HSC transplants...
October 9, 2018: Journal of Visualized Experiments: JoVE
Sara Farag, Pamela Frazzini Padilla, Katherine A Smith, Rebecca Flyckt, Michael L Sprague, Stephen E Zimberg
STUDY QUESTION: Is there perfusion to the fallopian tubes in ex-vivo and in-vivo uteri at the time of total laparoscopic hysterectomy (TLH), as observed using laser angiography with indocyanine green (ICG)? SUMMARY ANSWER: The fallopian tubes may have perfusion from the utero-ovarian vasculature alone. WHAT IS KNOWN ALREADY: The fallopian tubes are perfused by the uterine and utero-ovarian vessels. Perfusion can be measured using laser angiography with ICG...
December 1, 2018: Human Reproduction
Barbara B Warner
Bidirectional communication between the gut and brain is well recognized, with data now accruing for a specific role of the gut microbiota in that link, referred to as the microbiome-gut-brain axis. This review will discuss the emerging role of the gut microbiota in brain development and behavior. Animal studies have clearly demonstrated effects of the gut microbiota on gene expression and neurochemical metabolism impacting behavior and performance. Based on these changes, a modulating role of the gut microbiota has been demonstrated for a variety of neuropsychiatric disorders, including depression, anxiety, and movement including Parkinson's, and importantly for the pediatric population autism...
September 25, 2018: Pediatric Research
Yuka Nakamura, Motoshi Ichikawa, Hideaki Oda, Ieharu Yamazaki, Ko Sasaki, Kinuko Mitani
The RUNX1-EVI1 gene generated by the t(3;21) translocation encodes a chimeric transcription factor and is a causative gene in the development of de novo acute megakaryoblastic leukemia and leukemic transformation of hematopoietic stem cell tumors. Heterozygous RUNX1-EVI1 knock-in mice die in utero due to hemorrhage in the central nervous system and spinal cord and complete abolishment of definitive hematopoiesis in the fetal liver. On the other hand, the chimeric knock-in mouse develops acute megakaryoblastic leukemia...
November 2018: Leukemia Research
Peter P Roeleveld, David M Axelrod, Darren Klugman, Melissa B Jones, Nikhil K Chanani, Joseph W Rossano, John M Costello
The care of children with hypoplastic left heart syndrome is constantly evolving. Prenatal diagnosis of hypoplastic left heart syndrome will aid in counselling of parents, and selected fetuses may be candidates for in utero intervention. Following birth, palliation can be undertaken through staged operations: Norwood (or hybrid) in the 1st week of life, superior cavopulmonary connection at 4-6 months of life, and finally total cavopulmonary connection (Fontan) at 2-4 years of age. Children with hypoplastic left heart syndrome are at risk of circulatory failure their entire life, and selected patients may undergo heart transplantation...
November 2018: Cardiology in the Young
John S Riley, Lauren E McClain, John D Stratigis, Barbara E Coons, Haiying Li, Heather A Hartman, William H Peranteau
In utero hematopoietic cell transplantation (IUHCT) is a nonmyeloablative nonimmunosuppressive alternative to postnatal hematopoietic stem cell transplantation for the treatment of congenital hemoglobinopathies. Anti-HLA donor-specific Abs (DSA) are associated with a high incidence of graft rejection following postnatal hematopoietic stem cell transplantation. We determine if DSA present in the mother can similarly cause graft rejection in the fetus following IUHCT. Ten million C57BL/6 (B6, H2kb ) bone marrow cells were transplanted in utero into gestational day 14 BALB/c (H2kd ) fetuses...
September 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Maryam Borhani-Haghighi, Iraj Ragerdi Kashani, Yousef Mohamadi, Parichehr Pasbakhsh
OBJECTIVE: Prenatal brain injury results from undesirable circumstances during the embryonic development. Current endeavors for treating this complication are basically excluded to postnatal therapeutic approaches. Neural stem cell therapy has shown great promise for treating neurodevelopmental disorders. To our knowledge, this is the first study that investigates the therapeutic effect of in utero transplantation of neural stem cells (NSCs) in inflammation model of prenatal brain injury...
June 28, 2018: Journal of Chemical Neuroanatomy
Maria Isabel S Dinelli, Amélia M N Dos Santos, Lily Y Weckx, Maria Isabel de Moraes-Pinto
In utero exposure to immunosuppressive drugs might be a contraindication to rotavirus vaccine, but that may vary according to the immunosuppressive regimen. We evaluated 24 infants born to kidney transplanted mothers exposed to 3 immunosuppressants during pregnancy (prednisone, azathioprine, and tacrolimus or cyclosporine) and 31 control infants not exposed to these medications. No differences in adverse events were detected after rotavirus vaccination at 2 and 4 months.
June 11, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Jesse D Vrecenak, Erik G Pearson, Carlyn A Todorow, Haiying Li, Mark P Johnson, Alan W Flake
In utero hematopoietic cell transplantation (IUHCT) offers the potential to achieve allogeneic engraftment and associated donor-specific tolerance without the need for toxic conditioning, as we have previously demonstrated in the murine and canine models. This strategy holds great promise in the treatment of many hematopoietic disorders, including the hemoglobinopathies. Graft-versus-host disease (GVHD) represents the greatest theoretical risk of IUHCT and has never been characterized in the context of IUHCT...
May 23, 2018: Biology of Blood and Marrow Transplantation
Stefan P Tarnawsky, Wen-Mei Yu, Cheng-Kui Qu, Rebecca J Chan, Mervin C Yoder
Juvenile Myelomonocytic Leukemia (JMML) is a pediatric myeloproliferative neoplasm (MPN) that has a poor prognosis. Somatic mutations in Ptpn11 are the most frequent cause of JMML and they commonly occur in utero . Animal models of mutant Ptpn11 have probed the signaling pathways that contribute to JMML. However, existing models may inappropriately exacerbate MPN features by relying on non-hematopoietic-restricted Cre-loxP strains or transplantations into irradiated recipients. In this study we generate hematopoietic-restricted models of Ptpn11E76K-mediated disease using Csf1r-MCM and Flt3Cre...
April 24, 2018: Oncotarget
Francesca Macera, Lucia Occhi, Gabriella Masciocco, Marisa Varrenti, Maria Frigerio
BACKGROUND: Pregnancy after heart transplantation (HTx) may expose the recipient to hemodynamic and immunologic risks and the newborn to toxic effects of immunosuppressive therapy. Adequate preconception counseling is crucial to identify optimal timing and to modify immunosuppressive therapy to minimize risks for both the mother and the fetus. METHODS: We describe our experience with 12 pregnancies occurred in 11 women who had undergone HTx at our center. RESULTS: Pregnancies ran without severe complications or rejections, and none of the babies have shown major defects at birth...
September 2018: Transplantation
Milan Škorvaga, Matúš Durdík, Pavol Košík, Eva Marková, Marek Holop, Miroslav Kubeš, Judita Puškáčová, Alexandra Kolenová, Igor Belyaev
The first event in origination of many childhood leukemias is a specific preleukemic fusion gene (PFG) that arises, often in utero, in hematopoietic stem/progenitor cells (HSPC) from misrepaired DNA double strand break (DSB). An immanently elevated level of DSB and impaired apoptosis may contribute to origination and persistence of PFG and donor cell-derived leukemia in recipients of allogeneic transplantation of umbilical cord blood (UCB). We investigated DSB, apoptosis and PFG in the backtracked UCB cells of leukemic patients...
April 10, 2018: Oncotarget
Rachel Sagar, Lilian Walther-Jallow, Anna L David, Cecilia Götherström, Magnus Westgren
Purpose of Review: The aim of the study is to provide an overview on the possibility of treating congenital disorders prenatally with mesenchymal stromal cells (MSCs). Recent Findings: MSCs have multilineage potential and a low immunogenic profile and are immunomodulatory and more easy to expand in culture. Their ability to migrate, engraft and differentiate, or act via a paracrine effect on target tissues makes MSCs candidates for clinical therapies. Fetal and extra-fetal MSCs offer higher therapeutic potential compared to MSCs derived from adult sources...
2018: Current Stem Cell Reports
G Testa, G J McKenna, R T Gunby, T Anthony, E C Koon, A M Warren, J M Putman, L Zhang, G dePrisco, J M Mitchell, K Wallis, G B Klintmalm, M Olausson, L Johannesson
Uterus transplantation has proven to be a successful treatment for women with absolute uterine infertility, caused either by the absence of a uterus or the presence of a nonfunctioning uterus. We report the first birth of a healthy child following uterus transplantation in the United States, from a recipient of a uterus allograft procured from an altruistic living donor. Two major modifications from the previously reported live births characterized this uterus transplant. First, the transplanted uterus relied upon and sustained the pregnancy while having only the utero-ovarian vein as venous outflow...
May 2018: American Journal of Transplantation
Priyadarsini Kumar, Kewa Gao, Chuwang Wang, Christopher Pivetti, Lee Lankford, Diana Farmer, Aijun Wang
Hemophilia A (HA) is an X-linked recessive disorder caused by mutations in the factor VIII ( FVIII) gene leading to deficient blood coagulation. The current standard of care is frequent infusions of plasma-derived FVIII or recombinant B-domain-deleted FVIII (BDD-FVIII). While this treatment is effective, many patients eventually develop FVIII inhibitors that limit the effectiveness of the infused FVIII. As a monogenic disorder, HA is an ideal target for gene or cell-based therapy. Several studies have investigated allogeneic stem cell therapy targeting in utero or postnatal treatment of HA but have not been successful in completely correcting HA...
January 2018: Cell Transplantation
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