Transplantation Modules

Scaffolds, Transplantation Modules, Tissue Homing Devices and Stem Cells... 

To fabricate extracellular matrix equivalents with soft sugar (polysaccharide) hydrogels interpenetrated with networks of native extracellular matrix fragments and the synthesis of transplantation modules for higher resolution targeting is now a reality. 

Green, D.W., Ben-Nissan, B., 2010. Biomimetic applications in regenerative medicine scaffolds, transplantation modules, tissue homing device and stem cells. Chapter 21. In Tochilin, V., Amiji, M. (Eds.), Handbook of Materials for Nanomedicine. Pan Stanford Publishing Pte Ltd, Singapore, pp. 821-850. ISBN 978-981-4267-55-7. 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

The culture module greatly facilitated homogeneous distribution of seeded cells and cultivation of a large number of cells under identical conditions. In addition, the module required a smaller volume of medium than standard cell culture systems. Importantly, this modular system provides the great advantages of scalability and safety because cell processing can be performed in a closed system. Thus, the modules facilitate the production of cells that are safe for use in cell transplantation therapies. 

GC regulate a wide variety of immune cell functions. GC modulate cytokine expression, adhesion molecule expression and immune cell trafficking, immune cell maturation and differentiation, expression of chemoattractants and cell migration, and production of inflammatory mediators and other inflammatory molecules [35], At pharmacological concentrations, GC are routinely used as immunosuppressive therapeutic agents in many acute and chronic inflammatory and autoimmune diseases, in transplant patients and in the treatment of leukemias and lymphomas [reviewed in 29].. 

Awareness of immunotoxicology was stimulated by a comprehensive review by Vos in 1977, in which he provided evidence that a broad spectrum of xenobiotics alter immune responses in laboratory animals and subsequently may affect the health of exposed individuals. Several additional reviews, as well as national and international scientific meetings, have reinforced these early observations. In several studies, alteration of immune function was accompanied by increased susceptibility to challenge with infectious agents or transplantable tumor cells, indicating the resulting immune dysfunction in altered host resistance. Clinical studies in humans exposed to xenobiotics have confirmed the parallelism with immune dysfunction observed in rodents. The latter sections in this volume describe studies with xenobiotics that resulted in immune modulation in rodents and man. 

Transplant and allergy also intersect in indirect ways. Acute chest syndrome is a frequent complication in patients with sickle cell disease and has been recently reported to be exacerbated or precipitated by asthma and respiratory allergies. Since SCT can halt this pulmonary destruction process, ongoing investigation at our and other institutions is focused on determining genetic and cytokine pathways and modulators for asthma in sickle cell disease. 

Figure 2 Examples of coiled-coils used as engineering materials—transplantable oligomerization module (a) [24,25,27], epitope-displaying scaffold (b) [26], biorecognition element (c) [28], allosteric switch (d) [29], and self-replicating peptide (e) [30]. 

Modules Multicelled seed trays—also known as module trays—are available in plastic and polystyrene. The plastic ones are easier to remove plants from, and thus use again. Each seedling grows in its own individual "mini-pot," so its root system is not disturbed on transplanting. 

Until the role of echinacea in immune modulation is better defined, this agent should be avoided in patients with immune deficiency disorders (eg, AIDS, cancer), autoimmune disorders (eg, multiple sclerosis, rheumatoid arthritis), and patients with tuberculosis. While there are no reported drug interactions for echinacea, some preparations have a high alcohol content and should not be used with medications known to cause a disulfiram-like reaction. In theory, echinacea should also be avoided in persons taking immunosuppressant medications (eg, organ transplant recipients). 

Boockvar, J.A., Schouten, J., Royo, N., Millard, M., Spangler, Z., Castelbuono, D., Snyder, E., O Rourke, D., McIntosh, T. (2005). Experimental traumatic brain injury modulates the survival, migration, and terminal phenotype of transplanted epidermal growth factor receptor-activated neural stem cells. Neurosurgery, 56,163-71. 

In this study, the authors examined the immunomodulary functions of human MSCs by coculturing them with purified subpopulations of immune cells, and report that hMSCs alter the cytokine secretion profile of the host immune cells to induce a more antiinflammatory phenotype. The authors discuss and propose mechanisms underlying the immunomodulaiy functions of hMSCs in allogeneic transplantation. A shift from a proinflammatory environment toward an anti-inflammatory or tolerant cell environment would result in inflammation modulation, tolerance induction and reduction of allogeneic transplantation complications. 

The complement system is a humoral effector of inflammation which is activated by a cascade mechanism through the classical and/or alternative pathway [62]. Activation of the system is normally beneficial for the host. However, excessive activation may evoke pathological reaction in a variety of immunological and degenerative diseases and hyperacute rejection in transplantation. Therefore, the modulation of complement activity should be useful in the therapy of inflammatory diseases. 

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