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Live allograft bone cells

Federica Casiraghi, Norberto Perico, Giuseppe Remuzzi
The primary challenge in organ transplantation continues to be the need to suppress the host immune system long-term to ensure prolonged allograft survival. Long-term non-specific immunosuppression can, however, result in life-threatening complications. Thus, efforts have been pursued to explore novel strategies that would allow minimization of maintenance immunosuppression, eventually leading to transplant tolerance. In this scenario, bone marrow-derived mesenchymal stromal cells (MSC), given their unique immunomodulatory properties to skew the balance between regulatory and memory T cells, have emerged as potential candidates for cell-based therapy to promote immune tolerance...
December 27, 2017: Human Immunology
A-H Yang, C-C Loong, N-C Lin, C-Y Yang
BACKGROUND: Monoclonal gammopathy of renal significance denotes a spectrum of hematologic disorders that cause direct or indirect renal damage. CASE PRESENTATION: A 51-year-old man had received a living-donor kidney transplant from his wife in 2008. He had gradual increased proteinuria 4 years later. His renal biopsy results revealed cytoplasmic crystalloid inclusions in the podocytes. No crystalloid inclusion was found in other renal cells. Despite that immunofluorescent examination failed to show light-chain deposition, the serum immuno-electrophoresis revealed monoclonal immunoglobulin-Gκ...
December 2017: Transplantation Proceedings
C Krettek, J-D Clausen, C Neunaber
Cartilage defects in adult patients are so far incurable. Fresh osteochondral allograft (OCA) transplantation is based on the insertion of mature, living, mechanically sound hyaline cartilage into an osteochondral defect where it undergoes osseointegration. Intact hyaline cartilage of OCA does not cause immune reactions in the recipient. Many reports show that small OCA have good osseointegration and show good long-term results. These observations have been incorporated into the development of the fresh large (> 10 cm2 ) osteochondral shell allograft transplantation (FLOCSAT) concept, which is based on the following principles: 1) the thickness of the osseous layer should be kept as thin as possible (target < 6-8 mm) so that the transplant remains stable and fixable...
November 2017: Der Unfallchirurg
C Krettek, J-D Clausen, N Bruns, C Neunaber
Cartilage defects in adult patients do not heal well. Fresh osteochondral allograft (OCA) transplantation is based on mature, living, mechanically sound hyaline cartilage attached to a bone interface, which is brought into an osteochondral defect, where it becomes osseointegrated. According to current knowledge, intact hyaline cartilage tissue is immune privileged and does not, in contrast to bone, meniscus or ligaments, cause an immune reaction. The technique has the unique advantage of transplanting viable, mature and mechanically stable hyaline cartilage into the affected area...
November 2017: Der Unfallchirurg
Angus W Thomson, Abhinav Humar, Fadi G Lakkis, Diana M Metes
Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8+ memory T cell responses in the early post-transplant period...
October 31, 2017: Human Immunology
Rory McGoldrick, Arhana Chattopadhyay, Christopher Crowe, Grace Chiou, Kenneth Hui, Simon Farnebo, Christopher Davis, Anais Le Grand, Molly Jacobs, Hung Pham, James Chang
BACKGROUND: Suboptimal healing of the tendon-bone interface remains an unsolved problem. The authors hypothesized that (1) platelet-rich plasma and prolonged in vitro incubation will produce interface scaffolds with greater reseeding of viable adipose-derived stem cells; and (2) when implanted with extracellular matrix hydrogel, constructs will display superior in vivo strength repair and biocompatibility. METHODS: Achilles-calcaneal composite tendon-bone interface scaffold grafts were harvested from 30 Wistar rats...
December 2017: Plastic and Reconstructive Surgery
Zengfa Huang, Cheng Cheng, Jing Wang, Hui Wei, Xianzhe Liu, Xinxin Yan, Yan Zhou, Yunlu Liu, Shuhua Yang
BACKGROUND/AIMS: This experimental study aimed to evaluate the effect of low-concentration phosphoric acid on the surface structure of cortical allografts. METHODS: Allogenic cortical bones were obtained from femurs and tibias of New Zealand white rabbits. The bones were modified by treatment with various concentrations of phosphoric acid (10%, 20% or 30%) for 10, 30 or 60 minutes, then evaluated by the following methods: 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and LIVE/DEAD assay, alkaline phosphatase (ALP) assay, biomechanical properties testing, contact angle detection, quantitative real-time polymerase chain reaction (Q-PCR), western blotting and scanning electron microscopy (SEM)...
2017: Cellular Physiology and Biochemistry
Francesca Cardarelli, Vanesa Bijol, Anil Chandraker, Cindy Varga, Leonardo V Riella
The incidence of malignancy is greater in kidney transplant recipients compared to the general population, though the higher risk is not equally distributed to all types of cancers. In face of the increased longevity of renal transplant recipients, certain cancers, such as acute leukemias, are becoming more prevalent. Acute myeloid leukemia (AML) typically presents with cytopenias and infections, both common findings after kidney transplantation. Therefore, the diagnosis of AML may be initially overlooked in these patients...
December 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Bret H Clough, Eoin P McNeill, Daniel Palmer, Ulf Krause, Thomas J Bartosh, Christopher D Chaput, Carl A Gregory
BACKGROUND CONTEXT: Spine pain and the disability associated with it are epidemic in the United States. According to the National Center for Health Statistics, more than 650,000 spinal fusion surgeries are performed annually in the United States, and yet there is a failure rate of 15%-40% when standard methods employing current commercial bone substitutes are used. Autologous bone graft is the gold standard in terms of fusion success, but the morbidity associated with the procedure and the limitations in the availability of sufficient material have limited its use in the majority of cases...
March 2017: Spine Journal: Official Journal of the North American Spine Society
Yasuhiro Ishidou, Kanehiro Matsuyama, Eiji Matsuura, Takao Setoguchi, Satoshi Nagano, Hironori Kakoi, Masataka Hirotsu, Ichiro Kawamura, Takuya Yamamoto, Setsuro Komiya
Allograft bone is a widely used as a convenient tool for reconstructing massive bone defects in orthopedic surgery. However, allografts are associated with the risk of viral disease transmission. One of the viruses transmitted in this manner is human T-lymphotropic virus type 1 (HTLV-1), which is found worldwide but is unevenly distributed. The southwestern parts of Japan are a highly endemic for HTLV-1. We investigated the HTLV-1 seroprevalence in candidate allograft donors at the regional bone bank in Kagoshima, Japan during its first 5 years of service...
December 2016: Cell and Tissue Banking
M-O Timsit, J Branchereau, R Thuret, F Kleinclauss
OBJECTIVES: To report major findings that may build the future of kidney transplantation. MATERIAL AND METHODS: Relevant publications were identified through Medline ( and Embase ( database from 1960 to 2016 using the following keywords, in association, "bio-engineering; heterotransplantation; immunomodulation; kidney; regenerative medicine; xenotransplantation". Articles were selected according to methods, language of publication and relevance...
November 2016: Progrès en Urologie
Steffen Hartleif, Peter Lang, Rupert Handgretinger, Tobias Feuchtinger, Jörg Fuchs, Alfred Königsrainer, Silvio Nadalin, Ekkehard Sturm
Chronic IS is associated with significant morbidity in transplant recipients. Moreover, IS does not prevent chronic graft failure frequently. Allograft immune tolerance in LT can be induced by complete donor chimerism through allogenic HSCT combined with identical LDLT. This approach may exempt patients from chronic lifelong IS. However, it is unclear whether its benefits justify its risks. Here, we present three cases from our institution and analyze seven additional reports of children treated with HSCT/LDLT, all receiving HSCT due to hemato-oncological indications...
November 2016: Pediatric Transplantation
Giacomo Tommasi, Stefano Perni, Polina Prokopovich
Currently, the technique which provides the best chances for a successful bone graft, is the use of bone tissue from the same patient receiving it (autograft); the main limitations are the limited availability and the risks involved in removing living bone tissue, for example, explant site pain and morbidity. Allografts and xenografts may overcome these limitations; however, they increase the risk of rejection. For all these reasons the development of an artificial bone graft material is particularly important and hydrogels are a promising alternative for bone regeneration...
June 2016: Tissue Engineering. Part A
Michel Jourdan, Maïlys Cren, Peter Schafer, Nicolas Robert, Christophe Duperray, Laure Vincent, Patrice Ceballos, Guillaume Cartron, Jean-François Rossi, Jérôme Moreaux, Rajesh Chopra, Bernard Klein
Thalidomide, lenalidomide and pomalidomide have greatly improved the outcome of patients with multiple myeloma. However, their effects on plasma cells, the healthy counterpart of myeloma cells, are unknown. Here, we investigated lenalidomide effects on normal human plasma cell generation using an in vitro model. Lenalidomide inhibited the generation of pre-plasmablasts and early plasma cells, while it moderately affected plasmablast production. It also reduced the expression level of Ikaros, Aiolos, and IRF4 transcription factors, in plasmablasts and early plasma cells...
May 10, 2016: Oncotarget
Guang-Hui Pan, Zheng Chen, Lu Xu, Jing-Hui Zhu, Peng Xiang, Jun-Jie Ma, Yan-Wen Peng, Guang-Hui Li, Xiao-Yong Chen, Jia-Li Fang, Yu-He Guo, Lei Zhang, Long-Shan Liu
Calcineurin inhibitors, including tacrolimus, are largely responsible for advances in allotransplantation. However, the nephrotoxicity associated with these immunosuppressants impairs patients' long-term survival after renal allograft. Therefore, novel regimens that minimize or even eliminate calcineurin inhibitors could improve transplantation outcomes. In this pilot study, we investigated the use of low-dose tacrolimus in combination with mesenchymal stem cells (MSCs), which are immunosuppressive and prolong allograft survival in experimental organ transplant models...
March 15, 2016: Oncotarget
Curtis L Cetrulo, Tessa Drijkoningen, David H Sachs
PURPOSE OF REVIEW: The present review summarizes current data on the induction of immunologic tolerance through mixed hematopoietic chimerism relevant to applying this approach to vascularized composite allotransplantation. RECENT FINDINGS: Clinical allograft tolerance has been achieved recently for kidney transplants, using nonmyeloablative conditioning regimens and bone marrow transplantation from living donors. The mixed chimerism attained in these studies was either transient or durable, and both permitted tolerance of the renal allografts to be achieved across MHC-matched and MHC-mismatched barriers...
December 2015: Current Opinion in Organ Transplantation
Guillermo J Ruiz-Argüelles, Guillermo J Ruiz-Delgado, Oscar González-Llano, David Gómez-Almaguer
On the face of the lack of HLA-identical sibling stem cell donors for all individuals needing an allograft, the use of alternative donors is gaining popularity. Matched unrelated donors and cord bloods have become very expensive and unaffordable for most people living in developing countries. Grafting allogeneic haploidentical stem cells has become an option with a great future, mainly if the procedure is conducted in a way to cut down expenses, such as the use of reduced-intensity conditioning regimens, outpatient conduction of the procedures, and use of post-transplant cyclophosphamide...
December 2015: Current Oncology Reports
Zhanzhuo Li, Xin Xu, Ido D Weiss, Orit Jacobson, Philip M Murphy
Hematopoietic chimerism established by allogeneic bone marrow transplantation is known to promote donor-specific organ allograft tolerance; however, clinical application is limited by the need for toxic host conditioning and "megadoses" of donor bone marrow cells. A potential solution to this problem has been suggested by the observation that recipient bone marrow mobilization by the CXCR4 antagonist AMD3100 promotes chimerism in congenic bone marrow transplantation experiments in mice. Here we report that a single subcutaneous dose of 10 mg/kg AMD3100 in recipient C57BL/6 mice was able to enhance hematopoietic chimerism when complete MHC-mismatched BALB/c donor bone marrow cells were transplanted 1h after drug dosing...
October 2015: Transplant Immunology
Nahel Elias, A Benedict Cosimi, Tatsuo Kawai
PURPOSE OF REVIEW: This review summarizes the current state of clinical trials for tolerance induction of human leukocyte antigen-matched or mismatched renal allografts via peritransplant infusion of donor bone marrow-derived products. Recent efforts to apply infusion of expanded regulatory T-cell preparations to minimize immunosuppressive dosages are also reviewed. RECENT FINDINGS: Three centers in the United States have reported clinical trials for tolerance induction in recipients of living donor kidney transplants via donor hematopoietic stem cell transplantation...
August 2015: Current Opinion in Organ Transplantation
Sandra Geraghty, Jin-Qiang Kuang, Dana Yoo, Michelle LeRoux-Williams, C Thomas Vangsness, Alla Danilkovitch
BACKGROUND: Here, we describe the design and characterization of a novel, cryopreserved, viable osteochondral allograft (CVOCA), along with evidence that the CVOCA can improve outcomes of marrow stimulation for articular cartilage repair. METHODS: Histological staining was performed to evaluate the CVOCA tissue architecture. CVOCAs were tested for the presence of extracellular matrix (ECM) proteins and chondrogenic growth factors using ELISA. Cell viability and composition were examined via live/dead staining, fluorescence-activated cell sorting (FACS) analysis, and immunofluorescence staining...
2015: Journal of Orthopaedic Surgery and Research
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