Immunoisolation of transplants by entrapment in<sup>19</sup>F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity

Hillgärtner, Markus; Zimmermann, Heiko; Mimietz, S.; Jork, Anette; Thürmer, F.; Schneider, H; Nöth, Ulrich; Hasse, C.; Haase, Axel; Fuhr, G.; Rothmund, M.; Zimmermann, U.

doi:10.1002/(sici)1521-4052(199912)30:12<783::aid-mawe783>3.0.co;2-#

Cited by 19 publications

(11 citation statements)

References 42 publications

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“…Other factors such as stagnant water may be of equal importance. In the case of encapsulated cells (such as chondrocytes or C3H10T1/2-BMP fibroblasts, see above) it is even more difficult to predict "bound water" effects on For further details, see Hillgärtner et al 30 Note that only a part of the swelling curves is shown. Serum-alginate capsules were stable for about two years.…”

Section: Performance Of Biocompatible Ba 2+ -Alginate Microcapsules Fmentioning

confidence: 99%

“…6). 4,15,30 Proteins shift the water dispersion to about 110 MHz (FIG. 7), that is, to a frequency range where part of the water is mobile.…”

Section: Performance Of Biocompatible Ba 2+ -Alginate Microcapsules Fmentioning

confidence: 99%

“…Upon formation of the capsules, the divalent, reactive cations are released from the "cage" by UVirradiation. 30 This results in a uniform crosslinking throughout the bead that is The scan range is 6 × 6 µm 2 ; the height scale is 0-600 nm. Note that, in contrast to (A), the surface appears less smooth caused by fibrils.…”

Section: Performance Of Biocompatible Ba 2+ -Alginate Microcapsules Fmentioning

confidence: 99%

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A Novel Class of Amitogenic Alginate Microcapsules for Long‐Term Immunoisolated Transplantation

Zimmermann

Thürmer

Jork

et al. 2001

Annals of the New York Academy of Sciences

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In the light of results of clinical trials with immunoisolated human parathyroid tissue Ba2+‐alginate capsules were developed that meet the requirements for long‐term immunoisolated transplantation of (allogeneic and xenogeneic) cells and tissue fragments. Biocompatibility of the capsules was achieved by subjecting high‐M alginate extracted from freshly collected brown algae to a simple purification protocol that removes quantitatively mitogenic and cytotoxic impurities without degradation of the alginate polymers. The final ultra‐high‐viscosity, clinical‐grade (UHV/CG) product did not evoke any (significant) foreign body reaction in BB rats or in baboons. Similarly, the very sensitive pERK assay did not reveal any mitogenic impurities. Encapsulated cells also exhibited excellent secretory properties under in vitro conditions. Despite biocompatible material, pericapsular fibrosis is also induced by imperfect capsule surfaces that can favor cell attachment and migration under the release of material traces. This material can interact with free end monomers of the alginate polymers under formation of mitogenic advanced glycation products. Smooth surfaces, and thus topographical biocompatibility of the capsules (visualized by atomic force microscopy), can be generated by appropriate crosslinking of the UHV/CG‐alginate with Ba2+ and simultaneous suppression of capsule swelling by incorporation of proteins and/or perfluorocarbons (i.e., medically approved compounds with high oxygen capacity). Perfluorocarbon‐loaded alginate capsules allow long‐term non‐invasive monitoring of the location and the oxygen supply of the transplants by using 19F‐MRI. Transplantation studies in rats demonstrated that these capsules were functional over a period of more than two years.

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Section: Performance Of Biocompatible Ba 2+ -Alginate Microcapsules Fmentioning

confidence: 99%

“…6). 4,15,30 Proteins shift the water dispersion to about 110 MHz (FIG. 7), that is, to a frequency range where part of the water is mobile.…”

Section: Performance Of Biocompatible Ba 2+ -Alginate Microcapsules Fmentioning

confidence: 99%

Section: Performance Of Biocompatible Ba 2+ -Alginate Microcapsules Fmentioning

confidence: 99%

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A Novel Class of Amitogenic Alginate Microcapsules for Long‐Term Immunoisolated Transplantation

Zimmermann

Thürmer

Jork

et al. 2001

Annals of the New York Academy of Sciences

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“…It is because of this toxicity that most investigators used Ca 2+ as the cross-linking agent in the past. However, toxicity effects can be completely avoided if excess Ba 2+ ions after gelation are eliminated by precipitation with sulfate (35). Organic buffer molecules used frequently in the formation of Ba 2+ alginate beads (17,20,85) are also cytotoxic when released from the capsule during transplantation and must be replaced by biomolecules such as histidine (35,39).…”

Section: Fabrication Of Microcapsulesmentioning

confidence: 99%

Hydrogel-Based Non-Autologous Cell and Tissue Therapy

et al. 2000

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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.

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“…Inhomogeneous capsules can be prepared by removing the sodium ions or by adding an osmolyte, such as mannitol, to the gelling bath (Skjak-Braek et al, 1989). Alternatively, serum proteins or medically approved per uorocarbons can be incorporated into the gel network (Hillgärtner et al, 1999).…”

Section: Alginatementioning

confidence: 99%

Cell encapsulation technology as a therapeutic strategy for CNS malignancies

Visted¹

2001

Neuro-Oncology

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Neuro-Oncology n J U LY 2 0 0 1 201 Gene therapy using viral vectors has to date failed to reveal its de nitive clinical usefulness. Cell encapsulation technology represents an alternative, nonviral approach for the delivery of biologically active compounds to tumors. This strategy involves the use of genetically engineered producer cells that secrete a protein with therapeutic potential. The cells are encapsulated in an immunoisolating material that makes them suitable for transplantation. The capsules, or bioreactors, permit the release of recombinant proteins that may assert their effects in the tumor microenvironment. During the last decades, there has been signi cant progress in the development of encapsulation technologies that comprise devices for both macro-and microencapsulation. The polysaccharide alginate is the most commonly used material for cell encapsulation and is well tolerated by various tissues. A wide spectrum of cells and tissues has been encapsulated and implanted, both in animals and humans, indicating the general applicability of this approach for both research and medical purposes, including CNS malignancies. Gliomas most frequently recur at the resection site. To provide local and sustained drug delivery, the bioreactors can be implanted in the brain parenchyma or in the ventricular system. The development of comprehensive analyses of geno-and phenotypic pro les of a tumor (genomics and proteomics) may provide new and important guidelines for choosing the optimal combination of bioreactors and recombinant proteins for therapeutic use. Neuro-Oncology 3, 201-210, 2001 (Posted to Neuro-Oncology [serial online], Doc. 00-064,

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Immunoisolation of transplants by entrapment in¹⁹F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity

Cited by 19 publications

References 42 publications

A Novel Class of Amitogenic Alginate Microcapsules for Long‐Term Immunoisolated Transplantation

A Novel Class of Amitogenic Alginate Microcapsules for Long‐Term Immunoisolated Transplantation

Hydrogel-Based Non-Autologous Cell and Tissue Therapy

Cell encapsulation technology as a therapeutic strategy for CNS malignancies

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Immunoisolation of transplants by entrapment in19F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity

Cited by 19 publications

References 42 publications

A Novel Class of Amitogenic Alginate Microcapsules for Long‐Term Immunoisolated Transplantation

A Novel Class of Amitogenic Alginate Microcapsules for Long‐Term Immunoisolated Transplantation

Hydrogel-Based Non-Autologous Cell and Tissue Therapy

Cell encapsulation technology as a therapeutic strategy for CNS malignancies

Contact Info

Product

Resources

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Immunoisolation of transplants by entrapment in¹⁹F‐labelled alginate gels: production, biocompatibility, stability, and long‐term monitoring of functional integrity