The in vivo delivery of heterologous proteins by microencapsulated recombinant cells

Chang, Patricia L.; Raamsdonk, Jeremy M. Van; Hortelano, Gonzalo; Barsoum, Susan C; MacDonald, Nicole; Stockley, Tracy L.

doi:10.1016/s0167-7799(98)01250-5

Cited by 70 publications

(33 citation statements)

References 19 publications

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“…Although decreasing the solid stress induced by the surrounding gel may prolong the therapeutic functional period of cell-enclosing capsules as a result of cell growth within them, escape of cells into the surrounding environment is not optimal, from a safety point of view. In the case of transplanting a proliferative cell line in vivo, suppressing an excess proliferation of enclosed cells is vital for avoiding the risk of tumorigenesis (23).…”

Section: Discussionmentioning

confidence: 99%

Subsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy toward chemotherapeutic targeting to tumors

Sakai

Kono

Tanaka

et al. 2005

Molecular Cancer Therapeutics

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Localized activation of the prodrug ifosfamide in or close to tumors by implanting encapsulated ifosfamide-activating cells is an efficacious strategy for tumor therapy. The aim of this study was to evaluate the feasibility of subsieve-size agarose capsules for enclosing the cells in this application. Compared with many conventional microcapsules, subsieve-size agarose capsules are about onetenth the size and have both higher mechanical stability and allow better molecular exchangeability than other systems. Cells that have been genetically modified to express cytochrome P450 2B1 enzyme were encapsulated in subsieve-size agarose capsules of f90 Mm in diameter and implanted into preformed tumors in nude mice. Living cells were detected for >1 month after encapsulation in vitro and showed enzymatic activity (i.e., they were able to activate ifosfamide). More significant regression of preformed tumors was observed in the recipients implanted with cell-enclosing capsules compared with those implanted with empty capsules. These results suggest that the strategy of using subsievesize agarose capsules enclosing cytochrome P 450 2B1-expressing cells is feasible for tumor therapy by chemotherapeutic targeting in combination with ifosfamide administration. [Mol Cancer Ther 2005;4(11):1786 -90]

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Section: Discussionmentioning

confidence: 99%

Subsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy toward chemotherapeutic targeting to tumors

Sakai

Kono

Tanaka

et al. 2005

Molecular Cancer Therapeutics

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“…Enclosing these cells in imunoprotective devices would allow such nonautologous Time cells to be implanted into any host to deliver the desired gene product without triggering graft rejection. The advantages of this nonautologous method of gene delivery are: it does not require modification of the host's genome, thus providing additional measures of safety and cost saving; it provides ample material for quality assessment before implantation, a safety feature not available to most other forms of in vivo delivery (Chang et al, 1999;Tai and Sun, 1993). Read et al(2001) described a technique for the treatment of malignant brain tumors based on local delivery of endostatin from genetically engineered cells encapsulated in sodium alginate.…”

Section: Discussionmentioning

confidence: 99%

Preparation and in vitro studies of microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2

Jiang

Zhang

Peng

et al. 2005

J. Zhejiang Univ. Sci.

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Abstract:Objective: To prepare microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2 (TIMP-2), and investigate their biological characteristics in vitro. Methods: Chinese hamster ovary (CHO) cells were stably transfected with a human TIMP-2 expression vector, encapsulated in barium alginate microcapsules and cultured in vitro. Morphological appearance of the microcapsules was observed under a light microscope. Cell viability was assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Enzyme linked immunosorbent assay (ELISA) and reverse zymography were used to confirm the release of biologically active TIMP-2 from the microcapsules. Cryopreservation study of the microencapsulated cells was carried out using dimethyl sulfoxide (DMSO) as preservative agent. Results: The microcapsules appeared like a sphere with diameter of 300~600 µm. The surface of the capsule wall was clearly smooth. The microencapsulated cells survived well and kept proliferating over the 6 weeks observed. No significant difference in TIMP-2 secretion was found between encapsulated and unencapsulated cells. Reverse zymography confirmed the bioactivity of MMP (matrix metalloproteinase) inhibition of TIMP-2. The cryopreservation process did not damage the microcapsule morphology nor the viability of the cells inside. Conclusion: Microencapsulated engineered CHO cells survive at least 6 weeks after preparation in vitro, and secrete bioactive TIMP-2 freely from the microcapsules.

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“…[49] Drugs can be injected directly (bolus or infusion) via intrathecal catheters, by controlled release matrices 50 , microencapsulated chemicals 51 or recombinant cells 52 . The major problem with bolus injection is slower movement of compounds within the brain due to the limited diffusion coefficient.…”

Section: Intracerebral (Intraparenchymal) Drug Delivery To the Brainmentioning

confidence: 99%

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2011

IJPSR

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The blood-brain barrier (BBB) denies many therapeutic agents access to brain tumors and other diseases of the central nervous system (CNS). Despite remarkable advances in our understanding of the mechanisms involved in the development of the brain diseases and the actions of neuroactive agents, drug delivery to the brain remains a challenge. For more than 20 years, extensive efforts have been made to enhance delivery of therapeutic molecules across vascular barriers of the CNS. BBB allows a selective entry of nutrients and minerals across it and limits the entry of foreign substances like drugs as well as neuropharmaceutical agents. This makes the CNS treatment ineffective. The conventional drug delivery systems which release drug into general circulation fail to deliver drugs effectively to brain and is therefore not very useful in treating certain diseases that affect CNS including Alzheimer's disease, dementia, Parkinson's disease, mood disorder, AIDS, viral and bacterial meningitis. The current challenge is to develop drug delivery strategies that will allow the passage of drug molecules through the BBB in a safe and effective manner. The present review enlightens recent experimental and clinical findings in brain drug targeting that would give an insight to the researchers, academia and industrialists.

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The in vivo delivery of heterologous proteins by microencapsulated recombinant cells

Cited by 70 publications

References 19 publications

Subsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy toward chemotherapeutic targeting to tumors

Subsieve-size agarose capsules enclosing ifosfamide-activating cells: a strategy toward chemotherapeutic targeting to tumors

Preparation and in vitro studies of microencapsulated cells releasing human tissue inhibitor of metalloproteinase-2

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