Hydrogel-Based Non-Autologous Cell and Tissue Therapy

Abstract

Many diseases are closely tied to deficient or subnormal metabolic and secretory cell functions. Milder forms of these diseases can be managed by a variety of treatments. However, it is often extremely difficult or even impossible to imitate the moment-to-moment fine regulation and the complex roles of the hormone, factor or enzyme that is not sufficiently produced by the body. Immunoisolated transplantation is one of the most promising approaches to overcome the limitations of current treatments. Non-autologous (transformed) cell lines and allogeneic and xenogeneic cells/tissues that release the therapeutic substances are enclosed in immunoprotective microcapsules. The microcapsules avoid a lifetime of immunosuppressive therapy while excluding an immune response in the host. Research in this direction has shown the feasibility of microcapsules based on hydrogels (particularly of alginate) for transplantation of non-autologous cells and tissue fragments. Numerous technical accomplishments of the immunoisolation method have recently made possible the first successful long-term clinical applications. However, realizing the potential of immunoisolated therapy requires the use of several factors that have received limited attention in the past but are important for the formulation of hydrogel-based immunoisolation systems that are highly versatile, potentially economical and can gain medical approval.

Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I)

“…The alginate system 16,17 was selected because of its well-characterized ability to maintain the differentiated phenotype of chondrocytes, 18,19 the comparability of its negative charge density to that of native cartilage matrix, 20 its stability over short time periods 16 and its potential to allow allogeneic cell transplantation. 21 Alginate has been successfully used to deliver bone marrow-derived cells 22 and chondrocytes 23 to osteochondral articular cartilage defects in a rabbit model. In addition, alginate has been shown not to influence osteoarticular defect healing in the rabbit knee 24 and may protect transplanted allogeneic cells from immune rejection.…”

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

“…[194][195][196][197] Besides these biological factors, another approach taken to mimic the ECM properties is to directly conjugate ECM molecules to the scaffolds during fabrication or to use decellularized tissues as ECM scaffolds. [198][199][200][201] The ECM can be obtained from decellularized tissues and organs, for example, nerve, liver, and respiratory tract.…”

Long-Term Graft Function of Adult Rat and Human Islets Encapsulated in Novel Alginate-Based Microcapsules After Transplantation in Immunocompetent Diabetic Mice

“…The severe shortage of available human islets is another drawback of this promising therapeutic approach. A bioartificial pancreas consisting of islets immunoprotected by an alginate microcapsule provides an alternative approach to overcoming the rejection problem (2)(3)(4). Such immunoprotection is also appealing because it provides improved prospects of obtaining an abundant supply of human islets from ductal tissue (5) and the possibility of using xenogenic islets (e.g., porcine islets) (6).…”

“…Most importantly, graft survival is random and generally too limited for therapeutic application of these microcapsules (8 -10). The reasons for this are presumably the cytotoxicity of the polyamino acid and the mechanical instability of the microcapsules (2,11,12). Microcapsules made of alginate cross-linked with Ba 2ϩ do not share these disadvantages (13).…”