Approaches to Cell Delivery: Substrates and Scaffolds for Cell Therapy

Abstract

Retinal degeneration, associated with loss of photoreceptors, is the primary cause of permanent vision impairment, impacting millions of people worldwide. Age-related macular degeneration and retinitis pigmentosa are two common retinal diseases resulting in photoreceptor loss and vision impairment or blindness. Presently, available treatments can only delay the progress of retinal degeneration, and there are no treatments that can restore permanent vision loss. Research is underway to develop methods of regenerating the impaired retina by delivering photoreceptor precursor cells and retinal pigment epithelium to the subretinal space. Challenges to cell transplantation include limited survival upon implantation and the formation of abnormal cell architectures in vivo. Retinal tissue engineering shows immense promise and potential in treatment of retinal degeneration by employing scaffold-based delivery systems of retinal progenitor cells to the subretinal space. Scaffold delivery strategy has been shown to enhance the cell survival and direct cell differentiation in a variety of retinal degenerative models. In this chapter, we summarize the research findings on different scaffold- or substrate-based transplantation techniques used to deliver retinal progenitor/photoreceptor precursors and retinal pigment epithelial cells to the subretinal space.

White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies

“…A number of bioengineering approaches have been used for delivery for cardiac, retinal and corneal cell replacements (Cutts et al, 2015; Kundu et al, 2014; Ozcelik et al, 2014). The use of a natural or synthetic biodegradable matrix, usually as a membrane seeded with stem/progenitor cells, can provide the appropriate milieu for cell growth, and when placed directly on the target or diseased site of an organ (sometimes termed a ‘patch’ or ‘wrap’), resulting in efficient cell engraftment and homogenous cell distribution.…”

Stem cell based therapies for age-related macular degeneration: The promises and the challenges

“…Evidence has shown that using a polymer scaffold could offer better manipulation of the extracellular environment and afford the most appropriate degree of cell attachment, differentiation, and maintenance of apposite function (Tomita et al, 2005;Kador and Goldberg, 2012;Kundu et al, 2014). Current ongoing preclinical trials are applying various types of scaffolds for monolayer stem cells transplantation.…”

Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement

“…There are various techniques used to manufacture scaffolds for the subretinal space, such as particulate leaching, electrospinning and freeze drying, microfabrication, and solvent casting, the last 2 being the most used. 91 Regardless of their nature, scaffold size should range from 5 to 90 mm due to the limited subretinal compartment and be biocompatible, mechanically robust, flexible to be easily implantable, and porous to support formation of the polarized layer. Ideal scaffolds should (i) enable formation of a polarized RPE monolayer performing designated functions, (ii) have sufficient strength and flexibility to be transplanted at the back of the eye, (iii) support integration of RPE to Bruch's membrane, and lastly (iv) should be inert to the eye.…”