in vivo (Figure 50.3). Easy surgical manipulation, perhaps using specialized instrumentation, is of equal importance.28 An elegant facilitation of surgical delivery was recently proposed using magnetite nanoparticles ingested by RPE cells prior to transplantation.29 The RPE is a polarized epithelial cell and the prosthesis should therefore either readily facilitate nutrient flow or biodegrade rapidly, so that physiologic processes such as vitamin A, glucose, and fatty acid transport can be restored.

Taken together, while aspects of material science, culture techniques, instrumentation, and surgical delivery have been studied, a clinically applicable method of delivering cells on a prosthestic BM to restore RPE defects has not been developed thus far.3 Given that BM is frequently affected during RPE disease, the development of prosthetic BM materials is of great significance. Besides the obvious use as a carrier for RPE transplanation, upcoming stem cell-based therapies or stimulation of RPE wound healing may equally make use of such “instrument.”

STEM CELLS

Reports are accumulating about cells derived from mammalian stem cells, which acquire RPE-like phenotypes. These are very exciting new horizons for cellular replacement strategies of the RPE in the light of

immunologic challenges for homologous grafts and aging changes for autologous RPE. Prosthetic replacements of BM will likely be required for their delivery or long-term function in the subretinal space. Five different sources (embryonic stem cells, ciliary margin stem cells, adipose mesenchymal stromal cells, neural stem cells, and bone mar- row-derived cells) have been reported to date, of which two are briefly reviewed below.

Embryonic stem cells

Embryonic stem cells are derived from the inner cell mass of very-early- stage embryos. These cells have the potential to give rise to all cell types in the body. In vitro-generated RPE-like cells derived from monkey and human embryonic stem cells express RPE markers closely resembling cultured and in situ fetal RPE.30,31 Transplantation of these cells into RCS rats provides long-term rescue under immunosuppression without loss of RPE phenotype or signs of tumor formation.

Application in patients may, besides ethical concerns, be complicated by their expression of MHC molecules and thus cause immune rejection. Here, homologous recombination methods may reduce immunogenicity prior to differentiation or alternatively somatic cell nuclear transfer (SCNT) can create syngeneic transplants. The challenge of the SCNT field remains the efficacy of the cloned embryos to reach the blastocyst stage (when embryonic stem cells can be harvested from the