Intraspinal grafting of fibroblasts genetically modified by recombinant adenoviruses

Liu, Yi; Himes, B. Timothy; Tryon, B.; Moul, J.; Chow, S. Y.; Jin, Hao; Murray, Marion; Tessler, Alan; Fischer, Itzhak

doi:10.1097/00001756-199804200-00021

Cited by 33 publications

(24 citation statements)

References 4 publications

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“…Fibroblasts rapidly proliferate in culture, are extremely hardy and thus are very frequently used for ex vivo gene therapy and cell transplantation work. [22][23][24][25] Fibroblasts are already approved for human implantation. A tissue-engineered, Food and Drug Administration-approved, artificial skin containing fibroblast allografts harvested from neonatal skin samples has been available for treatment of nonhealing ulcers and other cutaneous defects.…”

Section: Discussionmentioning

confidence: 99%

Endovascular Treatment of Experimental Aneurysms by Use of Fibroblast-Coated Platinum Coils

Dai

Ding

Danielson

et al. 2007

Stroke

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Background and Purpose-The purpose of this study was to determine whether implanting exogenous fibroblasts on platinum coils could enhance intra-aneurysmal fibrosis. Hypotheses included: (1) fibroblast-coated (FBC) platinum coils can improve angiographic results after embolization; and (2) FBC platinum coils can accelerate histological healing of embolized aneurysms. Methods-Experimental aneurysms in rabbits were embolized with control platinum coils (nϭ18) or FBC coils (nϭ18).Subjects were euthanized at 14 days, 1 month, 3 months and 6 months after implantation. Digital subtraction angiography was used to evaluate stability after embolization. Histological samples were examined with a grading system (range, 0 to 12) based on neck and dome healing. Results-Histology total scores and fibrosis ratio at 14 days were significantly greater in the FBC coil group compared with controls (6.6Ϯ1.9 versus 2.5Ϯ1.1, 1.2Ϯ0.6% versus 0.2Ϯ0.3%, respectively; Pϭ0.0090). Cavities embolized with FBC coils showed cellular proliferation and thrombus organization, with an endothelialized membrane bridging the neck. There were no differences between groups in the later timepoints. The FBC coil group showed radiographic stability in 11 (61%) cases, coil compaction in 2 (11%) cases, and progressive occlusion in 5 (28%) cases. No progressive occlusion was seen in controls; 3 (17%) of 18 control cases exhibited coil compaction (Pϭ0.0546). Conclusions-FBC

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Section: Discussionmentioning

confidence: 99%

Endovascular Treatment of Experimental Aneurysms by Use of Fibroblast-Coated Platinum Coils

Dai

Ding

Danielson

et al. 2007

Stroke

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“…After grafting into the injured adult rat spinal cord without immune suppression nonencapsulated modified fibroblasts survive poorly and the survivors show decreased transgene expression (Liu et al, 1998;B.T. Himes et al, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

“…While rats in this study received one bolus dose of methylprednisolone to minimize the inflammatory response due to the injury, none of the animals were subjected to chronic immune suppression. Unencapsulated fibroblasts are rejected in the absence of immune suppression (Liu et al, 1998). Capsules containing FB/BDNF were transplanted into the lesion site of a partially hemisected cervical spinal cord of adult Sprague Dawley rats and harvested 2 weeks or 4 weeks after grafting.…”

Section: In Vitro Analysis Of Fb/bdnf Capsules Harvested From a Transmentioning

confidence: 99%

Grafting of Encapsulated BDNF-Producing Fibroblasts into the Injured Spinal Cord Without Immune Suppression in Adult Rats

Tobias

Dhoot

Wheatley

et al. 2001

Journal of Neurotrauma

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Grafting of genetically modified cells that express therapeutic products is a promising strategy in spinal cord repair. We have previously grafted BDNF-producing fibroblasts (FB/BDNF) into injured spinal cord of adult rats, but survival of these cells requires a strict protocol of immune suppression with cyclosporin A (CsA). To develop a transplantation strategy without the detrimental effects of CsA, we studied the properties of FB/BDNF that were encapsulated in alginate-poly-L-ornithine, which possesses a semipermeable membrane that allows production and diffusion of a therapeutic product while protecting the cells from the host immune system. Our results show that encapsulated FB/BDNF, placed in culture, can survive, secrete bioactive BDNF and continue to grow for at least one month. Furthermore, encapsulated cells that have been stored in liquid nitrogen retain the ability to grow and express the transgene. Encapsulated FB/BDNF survive for at least one month after grafting into an adult rat cervical spinal cord injury site in the absence of immune suppression. Transgene expression decreased within two weeks after grafting but resumed when the cells were harvested and re-cultured, suggesting that soluble factors originating from the host immune response may contribute to the downregulation. In the presence of capsules that contained FB/BDNF, but not cell-free control capsules, there were many axons and dendrites at the grafting site. We conclude that alginate encapsulation of genetically modified cells may be an effective strategy for delivery of therapeutic products to the injured spinal cord and may provide a permissive environment for host axon growth in the absence of immune suppression.

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“…After infection, approximately 50% of the cells expressed GFP. The cells were cultured as described previously, 27 using DMEM (Gibco, Invitrogen) with 10% fetal bovine serum (HyClone Laboratories, Inc.) and 1% Antibiotic-Antimycotic (Anti-Anti) Solution (Cellgro, Mediatech, Inc.) containing 10,000 IU/ml penicillin and 10,000 μg/ml streptomycin. The cells were thawed 12 days prior to surgery, and 1.2 × 10 6 viable cells were plated (p3) on 3 sterile petri dishes.…”

Section: Methodsmentioning

confidence: 99%

A pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N-isopropylacrylamide)-g-methylcellulose branched copolymers as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord

Conova

Vernengo

Jin

et al. 2011

SPI

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Object The authors investigated the feasibility of using injectable hydrogels, based on poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with polyethylene glycol (PEG) or methylcellulose (MC), to serve as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord. The primary aims of this work were to assess the biocompatibility of the scaffolds by evaluating graft cell survival and the host tissue immune response. The scaffolds were also evaluated for their ability to promote axonal growth through the action of released brain-derived neurotrophic factor (BDNF). Methods The in vivo performance of PNIPAAm-g-PEG and PNIPAAm-g-MC was evaluated using a rodent model of spinal cord injury (SCI). The hydrogels were injected as viscous liquids into the injury site and formed space-filling hydrogels. The host immune response and biocompatibility of the scaffolds were evaluated at 2 weeks by histological and fluorescent immunohistochemical analysis. Commercially available matrices were used as a control and examined for comparison. Results Experiments showed that the scaffolds did not contribute to an injury-related inflammatory response. PNIPAAm-g-PEG was also shown to be an effective vehicle for delivery of cellular transplants and supported graft survival. Additionally, PNIPAAm-g-PEG and PNIPAAm-g-MC are permissive to axonal growth and can serve as injectable scaffolds for local delivery of BDNF. Conclusions Based on the results, the authors suggest that these copolymers are feasible injectable scaffolds for cell grafting into the injured spinal cord and for delivery of therapeutic factors.

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Intraspinal grafting of fibroblasts genetically modified by recombinant adenoviruses

Cited by 33 publications

References 4 publications

Endovascular Treatment of Experimental Aneurysms by Use of Fibroblast-Coated Platinum Coils

Endovascular Treatment of Experimental Aneurysms by Use of Fibroblast-Coated Platinum Coils

Grafting of Encapsulated BDNF-Producing Fibroblasts into the Injured Spinal Cord Without Immune Suppression in Adult Rats

A pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N-isopropylacrylamide)-g-methylcellulose branched copolymers as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord

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