Gene Therapy Progress and Prospects: In tissue engineering

Polak, Julia M.; Hench, Larry L.

doi:10.1038/sj.gt.3302651

Cited by 32 publications

(18 citation statements)

References 98 publications

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“…Current research on the 3D culture system is more vital and promising than ever. [44][45][46][47] The utility of 3D systems is underscored by their potential use in drug delivery, study of metastasis, and tissue engineering for therapeutic purposes. The advantage of the 3D cell culture system is its defined geometry that makes it possible to directly relate structure to function and that approximates an in vivo state more closely by allowing spatial resolution.…”

Section: Discussionmentioning

confidence: 99%

Engineering Retina from Human Retinal Progenitors (Cell Lines)

Dutt

Cao

2009

Tissue Engineering Part A

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Retinal degeneration resulting in the loss of photoreceptors is the leading cause of blindness. Several therapeutic protocols are under consideration for treatment of this disease. Tissue replacement is one such strategy currently being explored. However, availability of tissues for transplant poses a major obstacle. Another strategy with great potential is the use of adult stem cells, which could be expanded in culture and then utilized to engineer retinal tissue. In this study, we have explored a spontaneously immortalized human retinal progenitor cell line for its potential in retinal engineering using rotary cultures to generate three-dimensional (3D) structures. Retinal progenitors cultured alone or cocultured with retinal pigment epithelial cells form aggregates. The aggregate size increases between days 1 and 10. The cells grown as a 3D culture rotary system, which promotes cell-cell interaction, retain a spectrum of differentiation capability. Photoreceptor differentiation in these cultures is confirmed by significant upregulation of rhodopsin and AaNat, an enzyme implicated in melatonin synthesis (immunohistochemistry and Western blot analysis). Photoreceptor induction and differentiation is further attested to by the upregulation of rod transcription factor Nrl, Nr(2)e(3), expression of interstitial retinal binding protein, and rhodopsin kinase by reverse transcription-polymerase chain reaction. Differentiation toward other cell lineages is confirmed by the expression of tyrosine hydroxylase in amacrine cells, thy 1.1 expression in ganglion cells and calbindin, and GNB3 expression in cone cells. The capability of retinal progenitors to give rise to several retinal cell types when grown as aggregated cells in rotary culture offers hope that progenitor stem cells under appropriate culture conditions will be valuable to engineer retinal constructs, which could be further tested for their transplant potential. The fidelity with which this multipotential cell line retains its capacity to differentiate into multiple cell types holds great promise for the use of tissue-specific adult stem cells for therapy.

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Section: Discussionmentioning

confidence: 99%

Engineering Retina from Human Retinal Progenitors (Cell Lines)

Dutt

Cao

2009

Tissue Engineering Part A

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“…Wilson et al [10] reported that macrophages in which the NF-ĸB pathway was inhibited by transduction with dominant-negative IĸB developed anti-inflammatory properties and reduced glomerular injury in nephrotoxic serum nephritis. Despite genetic manipulation of macrophages being applied successfully in experimental models of renal disease, major obstacles to clinical application of this technology include the danger of viral vectors and difficulty of controlling levels of gene expression in vivo [11]. Macrophages modified ex vivo with IFN-γ into M1 and infused into leucopenic rats substantially augmented renal injury, an effect which could be blocked with glucocorticoids [12].…”

Section: Introductionmentioning

confidence: 99%

Transfused Macrophages Ameliorate Pancreatic and Renal Injury in Murine Diabetes Mellitus

Zheng

Wang

Cao

et al. 2011

Nephron Exp Nephrol

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Background: Alternatively activated macrophages (M2 macrophages) are able to reduce renal injury in murine adriamycin nephropathy. However, the effect of M2 macrophages in other renal diseases such as diabetic nephropathy remains unknown. Methods: Macrophages were separated from splenocytes and polarized with IL-4 and IL-13 into a protective phenotype. Mice underwent adoptive transfer with M2 macrophages, and then diabetes was induced by tail vein injection with streptozotocin (STZ). Blood glucose levels were monitored daily. Mice were sacrificed at week 10 after STZ. Renal function and histopathological injury were assessed quantitatively. Results: Transfused M2 macrophages accumulated progressively in kidneys for up to 10 weeks after STZ. Kidneys from diabetic mice transfused with M2 macrophages had less tubular atrophy, glomerular hypertrophy and interstitial expansion than did control diabetic mice. M2 macrophages suppressed the development of interstitial fibrosis. In addition, the degree of pancreatic islet injury, as assessed by insulin staining, haemoglobin A1c and blood glucose was reduced after transfusion of M2 macrophages. In vivo, activation of kidney endogenous macrophage cytokine expression was inhibited by M2 macrophages. Conclusion: Our findings show that M2 macrophages can protect against islet and renal injury in streptozotocin-induced diabetes, providing a potential therapeutic strategy for diabetes and diabetic nephropathy.

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“…Gene therapy has shown promising results in the field of tissue engineering [33,34]. It could potentially utilize biological principles to guide cellular behaviors into scaffolds.…”

Section: In Situ Transfection Of Multilayers On the Poly(lactic Acid)mentioning

confidence: 99%