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In utero transplantation

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https://www.readbyqxmd.com/read/30371676/intravenous-and-intra-amniotic-in-utero-transplantation-in-the-murine-model
#1
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
https://www.readbyqxmd.com/read/30304437/fallopian-tube-perfusion-in-ex-vivo-and-in-vivo-laparoscopic-hysterectomy-specimens-potential-application-for-uterine-transplantation
#2
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
https://www.readbyqxmd.com/read/30283047/the-contribution-of-the-gut-microbiome-to-neurodevelopment-and-neuropsychiatric-disorders
#3
REVIEW
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
https://www.readbyqxmd.com/read/30278283/runx1-evi1-induces-dysplastic-hematopoiesis-and-acute-leukemia-of-the-megakaryocytic-lineage-in-mice
#4
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...
September 26, 2018: Leukemia Research
https://www.readbyqxmd.com/read/30223915/hypoplastic-left-heart-syndrome-from-fetus-to-fontan
#5
REVIEW
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
https://www.readbyqxmd.com/read/30021770/pre-existing-maternal-antibodies-cause-rapid-prenatal-rejection-of-allotransplants-in-the-mouse-model-of-in-utero-hematopoietic-cell-transplantation
#6
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
https://www.readbyqxmd.com/read/29959975/embryonic-intraventricular-transplantation-of-neural-stem-cells-augments-inflammation-induced-prenatal-brain-injury
#7
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
https://www.readbyqxmd.com/read/29890028/safe-administration-of-rotavirus-vaccine-in-a-cohort-of-infants-exposed-to-immunosuppressive-drugs-during-gestation
#8
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
https://www.readbyqxmd.com/read/29802901/preclinical-canine-model-of-graft-versus-host-disease-after-in-utero-hematopoietic-cell-transplantation
#9
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
https://www.readbyqxmd.com/read/29774106/hematopoietic-restricted-ptpn11e76k-reveals-indolent-mpn-progression-in-mice
#10
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
https://www.readbyqxmd.com/read/29762460/a-new-life-motherhood-after-heart-transplantation-a-single-center-experience-and-review-of-literature
#11
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
https://www.readbyqxmd.com/read/29721197/backtracked-analysis-of-preleukemic-fusion-genes-and-dna-repair-foci-in-umbilical-cord-blood-of-children-with-acute-leukemia
#12
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
https://www.readbyqxmd.com/read/29600162/fetal-mesenchymal-stromal-cells-an-opportunity-for-prenatal-cellular-therapy
#13
REVIEW
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
https://www.readbyqxmd.com/read/29575738/first-live-birth-after-uterus-transplantation-in-the-united-states
#14
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
https://www.readbyqxmd.com/read/29562772/in-utero-transplantation-of-placenta-derived-mesenchymal-stromal-cells-for-potential-fetal-treatment-of-hemophilia-a
#15
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
https://www.readbyqxmd.com/read/29552016/-in-utero-exposure-to-exosomal-and-b-cell-alloantigens-lessens-alloreactivity-of-recipients-lymphocytes-rather-than-confers-allograft-tolerance
#16
Jeng-Chang Chen, Liang-Shiou Ou, Cheng-Chi Chan, Ming-Ling Kuo, Li-Yun Tseng, Hsueh-Ling Chang
According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29489501/prenatal-transplantation-of-human-amniotic-fluid-stem-cells-for-spinal-muscular-atrophy
#17
Shao-Yu Peng, Sheng-Wen S Shaw
PURPOSE OF REVIEW: To review the current medical and stem-cell therapy for spinal muscular atrophy (SMA) and prenatal transplantation of amniotic fluid stem cells in the future. RECENT FINDINGS: SMA is an autosomal recessive inheritance of neurodegenerative disease, which is caused of the mutation in survival motor neuron. The severe-type SMA patients usually die from the respiratory failure within 2 years after birth. Recently, researchers had found that 3-methyladenine could inhibit the autophagy and had the capacity to reduce death of the neurons...
April 2018: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29482456/long-term-hematopoietic-engraftment-of-congenic-amniotic-fluid-stem-cells-after-in-utero-intraperitoneal-transplantation-to-immune-competent-mice
#18
Panicos Shangaris, Stavros P Loukogeorgakis, Michael P Blundell, Eleni Petra, Steven W Shaw, Durrgah L Ramachandra, Panagiotis Maghsoudlou, Luca Urbani, Adrian J Thrasher, Paolo De Coppi, Anna L David
Clinical success of in utero transplantation (IUT) using allogeneic hematopoietic stem cells (HSCs) has been limited to fetuses that lack an immune response to allogeneic cells due to severe immunological defects, and where transplanted genetically normal cells have a proliferative or survival advantage. Amniotic fluid (AF) is an autologous source of stem cells with hematopoietic potential that could be used to treat congenital blood disorders. We compared the ability of congenic and allogeneic mouse AF stem cells (AFSC) to engraft the hematopoietic system of time-mated C57BL/6J mice (E13...
April 15, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29469650/prenatal-androgen-exposure-causes-hypertension-and-gut-microbiota-dysbiosis
#19
Shermel B Sherman, Nadeen Sarsour, Marziyeh Salehi, Allen Schroering, Blair Mell, Bina Joe, Jennifer W Hill
BACKGROUND: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant...
2018: Gut Microbes
https://www.readbyqxmd.com/read/29372042/intrauterine-xenotransplantation-of-human-wharton-jelly-derived-mesenchymal-stem-cells-into-the-liver-of-rabbit-fetuses-a-preliminary-study-for-in-vivo-expression-of-the-human-liver-genes
#20
Leila Rezaeian, Seyed Ebrahim Hosseini, Mehdi Dianatpour, Mohammad Amin Edalatmanesh, Nader Tanideh, Asghar Mogheiseh, Amin Tamadon
Objectives: End-stage hepatic failure is a potentially life-threatening condition for which orthotopic liver transplantation is the only effective treatment. However, a shortage of available donor organs for transplantation each year results in the death of many patients waiting for liver transplantation. Xenotransplantation, or the transplantation of cells, tissues, or organs between different species, was proposed as a possible solution to the worldwide shortage of human organs and tissues for transplantation...
January 2018: Iranian Journal of Basic Medical Sciences
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