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The Host Response to Grafts and Transplantation Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Most of the grafts that are transplanted are allografts, or grafts between individuals of the same species. Such individuals are not genetically identical unless they are identical twins. Allografts can come from twins, parents, relatives, or unrelated individuals. Transplantation of grafts between identical siblings, or between mice of the same strain, are termed syngeneic. Not many humans needing grafts are lucky enough to have an identical twin to supply grafts. Such grafts, when available, are not recognized as foreign by the host because they are the same as self, i.e, not foreign. The term autograft means that the grafted tissue is from the same individual, such as skin transplanted from one part of the body to cover a part that has been damaged by a burn. Finally, the term xenograft refers to grafts between individuals of different species. Successful xenografting is a desirable goal since there are not enough human organs to be transplanted into all of the individuals that need an organ graft. Miniature pigs, because they are of a similar size with a similar circulation to that of humans, have been farmed to use as organ donors for humans. Recently, ethical review boards have blocked transplantation of organs between animals and humans because of the possibility of transmission of animal retro viruses to humans. An example of such a transfer is the human immunodeficiency virus that causes AIDS. AIDS is believed to have been transferred from chimpanzees, in whom it does not cause disease, to humans, in whom it does.
The Use of 4-HC in Autologous Purging
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
Scott D. Rowley, Janice M. Davis
A phase I dose-escalation trial in humans, primarily undergoing transplantation for the treatment of acute leukemia, determined 100 mg/ml to be the “maximum safe concentration” of 4-HC.10 For this trial, buffy coat cells separated from the grafts were incubated for 30 min at 37°C and frozen without washing. Although in vivo hematopoietic progenitor cell growth, using an agar-based assay, was virtually eliminated, all evaluable patients up to that 4-HC concentration engrafted. A dose response in engraftment kinetics was found. Patients treated at higher 4-HC concentrations experienced longer aplasias. Several patients receiving marrows treated with 120 μg/ml of 4-HC had no evidence of recovering hematopoiesis 21 d after transplantation, and were “rescued” with grafts treated at a lower concentration of 4-HC. Subsequently, we initiated 2 phase II trials in acute lymphoblastic leukemia (ALL),1 and acute nonlymphoblastic leukemia (ANLL),11 using the dose (100 μg/ml) and incubation techniques developed in the phase I trial. The relapse rate for patients treated for ALL exceeded 80%; however, the rate reported for patients with ANLL was about 45%, or approximately what would be expected in syngeneic transplantation (without tumor contamination of the graft, but also without graft-vs.-leukemia effect).
Retroviral Gene Transfer in Autologous Bone Marrow and Stem Cell Transplantation
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Rafat Abonour, Kenneth Cornetta
Introduction of the MDR-1 cDNA into transgenic mice or murine hematopoietic progenitor cells via retroviral gene transfer has lead to chemo-protection in vitro and in vivo (Galski et al. 1989; McLachlin et al. 1990s Choi et al. 1991; Sorrentino et al. 1992). In the setting of murine syngeneic transplantation, Licht et al. (1995) detected human MDR-1 DNA in up to 78% of peripheral blood cells following transplantation with vector-transduced marrow. Vector was detectable for up to 6 months after transplantation, but longterm vector expression was variable and short-lived in the absence of in vivo selection.
Applications of mesenchymal stem cells in ocular surface diseases: sources and routes of delivery
Published in Expert Opinion on Biological Therapy, 2023
Mohammad Soleimani, Ahmad Masoumi, Bita Momenaei, Kasra Cheraqpour, Raghuram Koganti, Arthur Y Chang, Mahmoud Ghassemi, Ali R Djalilian
Hypothetically, MSCs can be isolated from several tissues in the human body. However, there are practical limitations regarding the invasiveness and risk to the patient from obtaining the cells. The two main sources of MSCs are currently bone marrow and adipose tissue [50]. However, MSCs can also be procured from dental pulps, amniotic membrane, and the umbilical cord [51]. Nevertheless, the difficulty and potential adverse effects of the harvesting procedure should be considered before choosing where to obtain the cells. Treacy et al. found that the systemic administration of allogeneic and third party-derived BM-MSCs prolong the survival of corneal allografts in a rat model. This outcome was not observed with systemic injection of syngeneic cells. The authors hypothesized that treatment with allogeneic and third party MSCs suppresses the peripheral immune response and modulates the host’s immune reaction. This event may result in an immunoregulatory micro-environment in the corneal allograft [52].
Combining the past and present to advance immuno-radiotherapy of cancer
Published in International Reviews of Immunology, 2023
Ioannis M. Koukourakis, Michael I. Koukourakis
In the 70’s, several attempts had been made to enhance the immunogenicity of syngeneic cancer cell transplantation, including injection of subthreshold doses of undamaged living cancer cells or tumor cells pretreated with vibrio cholera neuraminidase [51]. It had been postulated that neuraminidase removes the sialic acid from the surface of tumor cells by breaking its 2-8-glucosidic linkages with mucopolysaccharides of the cell membrane, enhancing the presentation of cancer cell antigens to immune cells [52, 53]. The intra-lymphatic administration of cancer cells gained attention, as it was thought that direct injection of cancer cells into the nodes where lymphocytes reside waiting for their activation would be a better way to immunize hosts. In 1976, Juillard et al. reported a study on the intra-lymphatic infusion of irradiated with 10 Gy and preincubated with neuraminidase tumor cells from a poorly differentiated lymphocytic lymphoma growing on dogs [54]. The involved nodes showed a rapid decrease in their size that continued for about two months before starting re-growing, while a second wave of reduction was noted some weeks later.
Use of the PRECICE nail for distraction osteogenesis after tumor resection
Published in Expert Review of Medical Devices, 2022
Nelson Merchan, Raed I. Narvel, I. Leah Gitajn, Eric R. Henderson
Limb preservation surgery has largely replaced ablative options for extremity cancers. Reconstruction options have changed very little in the last 30+ years and generally deliver outcomes that are inferior to patients’ pre-disease state [26]. Furthermore, reconstruction options that require implantation of foreign material – metallic endoprosthesis or structural allograft – are prone to surgical failure via numerous modes [27,28]. It is our opinion that employing reconstruction strategies that allow a native, biological healing process to facilitate restoration of the structural and functional requirements of the limb is more advantageous for patients and should be employed whenever possible. At present, there is no means to re-grow a patient’s articular surface, but the technique of distraction osteogenesis (bone transport) does offer patients a pathway to a syngeneic biological reconstruction option.