Cell delivery

Yang J, Yamato M, Nishida K, Ohki T, Kanzaki M, Sekine H, Shimizu T, Okano T (2006) Cell delivery in regenerative medicine the cell sheet engineering approach. J Control Release 116 193-203. 

Colin M, Maurice M, Trugnan G, et al. Cell delivery, intracellular trafficking and expression of an integrin-mediated gene transfer vector in tracheal epithelial cells. Gene Ther 2000 7(2) 139-152. 

Barth H, Blocker D, Aktories K. The uptake machinery of clostridial actin ADP-ribosylating toxins—a cell delivery system for fusion proteins and polypeptide drugs. Naunyn Schmiedebergs Arch Pharmacol 2002 366(6) 501-512. 

The major drawback to using an intravenous route of cell delivery would be the possibility that the therapeutic cells would become trapped in the microvasculature of the lungs, liver, and lymphoid tissues. This theoretical limitation of systemic transvenous delivery of stem cells has been confirmed experimentally. In a study by Toma et al. [97], human MSCs were injected into the left ventricular cavity of experimental mice 4 days later, an estimated 0.44% of the injected cells remained in the myocardium, and the rest had localized to the spleen, liver, and lungs. Other studies using the systemic delivery approach have produced similar results, with very low local cell retention rates of less than 5% [98, 99]. Thus, the transvenous delivery route appears unlikely to achieve the local cell concentration needed to produce a significant therapeutic benefit. 

Fig. 7.9 Intraeoronary stem cell delivery. The technique is similar to that for coronary angioplasty, which involves over-the-wire positioning of an angioplasty balloon in a coronary artery. Coronary blood flow is transiently stopped for 2-4 min while stem cells are infused under pressure,...

Few studies have compared the different modes of cell delivery. Hou et al. [132] have described the fate of peripheral blood mononuclear cells (PBMNCs) 1 h after direct surgical injection,... 

Together, these data suggest that none of these three delivery strategies are more than modestly efficient at delivering cells to targeted regions. This is of special concern in the case of intracoronary delivery, which is the stem cell delivery method most widely used after AML This has several important clinical implications for the... 

Mooney DJ, Mazzoni CL, Organ GM, Puelacher WC, Vacanti JP, Langer R (1994) in Mikos AG, Murphy RM, Bernstein H, Peppas NA (Ed) Biomaterials for Drug and Cell Delivery, MRS Symposinm Proceedings, Vol 331, Materials Research Society, Pittsburgh, Pennsylvania, pp 47-52... 

As a part of our program to develop new adjuvants for the into-cell delivery of phosphorylated nucleotide-type antiviral agents (see Section 3 of this chapter), we became interested in developing a sapphyrin-based approach to phosphate anion chelation. As proved true for halide anion recognition, important initial support for the idea that sapphyrins could function as phosphate anion receptors came from single crystal X-ray diffraction studies. In fact, to date, five X-ray structures of sapphyrin-phosphate complexes have been obtained. ... 

Keywords Cationic lipids Cell delivery Dendrimers Gene therapy... 

Grosse S, Aron Y, Honore I, Thevenot G, Danel C, Roche A-C, Monsigny M, Fajac I (2004) Lactosylated polyethylenimine for gene transfer into airway epithelial cells role of the sugar moiety in cell delivery and intracellular trafficking of the complexes. J Gene Med 2004 (6) 345-356... 

Patel ZS, Mikos AG. Angiogenesis with biomaterial-based drug- and cell-delivery systems. Journal of Biomaterials Science. Polymer Edition 2004, 15, 701-726. 

Another novel cardiovascular therapy that has recently come into play is the use of stem cell delivery. These approaches have thus far involved the use of gene delivery mechanisms to essentially force embryonic stem cells into cardiomyocyte differentiation with the goal of producing a cardiac pace-making cell (Arruda et al., 2004). Researchers are also developing methods for utilizing seeded adult mesenchymal stem cells as an implanted base to act as a depot for the delivery of localized gene therapies (Arruda et al., 2004). 

One major drawback with surgical cell delivery is the invasiveness of the delivery process. The need for thoracotomy or sternotomy limits the potential patient population—in that patients with greatly reduced LV function will not easily tolerate this procedure. 

A serious deleterious outcome associated to date primarily with myoblasts (and with thawed BM in chemotherapy patients) (50) is the incidence of cardiac electrical instability for a presumed transient period after cell delivery. These early reports of electrical instability in patients after the receipt of autologous skeletal myoblasts have led to doubts about the safety of these cells as a treatment in the injured heart. Patients who received myoblasts in the earliest clinical studies (33,38) were extremely ill patients with an expected high potential for negative electrical events. In fact, many of the patients who were included in the early trials met the Multicenter Automatic Defibrillator Implantation Trial MADIT-II criteria, which were presented after those trials began, and suggested that all patients who met those criteria be treated with AlCDs. As a result, in more recent clinical studies, many investigators have only enrolled patients who receive AlCDs... 

In contrast to that of myoblasts and mesenchymal cells, BM mononuclear or EPC delivery is primarily intracoronary (9), Presumably owing to the much smaller size of these angiogenic cells, their delivery has not been associated with significant adverse ischemic events, However, BM cell delivery has been associated with the theoretical potential for angiogenesis at unwanted sites, such as in occult tumors or retina, This unanticipated and potentially serious consequence illustrates our need to learn from our previous gene therapy colleagues and to expect the unexpected in this field,... 

One of the goals of preclinical evaluation is to improve efficacy and safety by optimizing both the method of cell delivery and the site of cell delivery... 

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