Immunoisolation

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Immunoisolation

• Beth Zielinski-Habershaw, Ph.D.

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Why organ replacement?

• Irreversible organ/tissue damage
• Metabolic insufficiencies
• Molecular dysfunction
• Solution
• Donor transplantation
• Artificial repair and replacement

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Need?
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Donor transplantation

• Pros
• Replicates tissues natural function
• Cons
• Supply constraints
• Immune rejection

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Artificial repair and replacement

• Pros
• No immune suppression required
• No supply constraints
• Cons
• Full replacement of function?
• Biocompatibility

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The alternative

• Immunoisolation

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Immunoisolation

• Sequestration of cells within a semi-permeable
  membrane
• Delivery of therapeutic agents to host by
  encapsulated cells
• Separation between host immune components and
  encapsulated cells

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Bioartificial organs

• History
• 1970
• Chick et al
• Bioartificial pancreas
• 1980
• Lim and Sun
• Alginate-encapsulated allogeneic islets
• 1980-present
• Immunoisolatory therapy for treatments of
  diabetes, chronic pain, neurodegenerative
  diseases, cancer

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Theory
Macroencapsulation
Microencapsulation
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Issues

• Membrane characteristics
• Pore size
• Thickness
• Tortuosity
• Polymer/device characteristics
• Thermomechanical stability
• Geometry
• Biodegradability
• Retrievability
• Scale-up

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Issues

• Cells/Cell sourcing
• Allogeneic or xenogeneic?
• Primary post-mitotic cells?
• Mitotically active cells?
• Genetically engineered cell lines?

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Capsule format

• Microcapsules
• Interfacial coacervation
• Cells entrapped during manufacturing of
  microcapsule device
• Macrocapsules
• Co-extruded phase inversion
• Simultaneous fiber formation and loading
• Phase inversion and filling
• Cells encapsulated following formation of stock
  fiber

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Matrices

• Adherent and non-adherent cell types?
• Growth or protein production enhancement?
• Viability?
• Preloading of desired matrix?
• Simultaneous loading of matrix and cells?
• Simultaneous formation of capsules with matrix
  and cells included?

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Microencapsulation techniques
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Macroencapsulation techniques

• Co-extrusion
• Cells extruded into fiber along with polymer
• Exposure to organic solvents
• Post-extruded filling
• Loading of preformed capsules
• Sealing of capsule ends

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Host immune responses

• Cellular
• Macrophage
• Giant cells/FBR
• Neutrophils
• Antibody
• IgM
• IgG
• IgA?
• Complement
• Alone or in conjunction with cellular or antibody
  responses

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Host immune responses
Antibody response
Macrophage/neutrophil activation Complement
activation
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Current Applications

• Chronic Pain
• Diabetes
• Cancer
• ALS
• Neurotrophic release

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Current applications

• Neurotech USA
• RenaMed Therapeutics

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Future directions

• Microvascularization
• Biodegradable microspheres
• Photopolymerized conformal coatings
• Programmable death