Tissue Eng Regen Med.  2017 Feb;14(1):39-47. 10.1007/s13770-016-0021-2.

Generation of Retinal Progenitor Cells from Human Induced Pluripotent Stem Cell-Derived Spherical Neural Mass

Affiliations
  • 1Department of Ophthalmology, Korea University, College of Medicine, 126-1 Anam-dong 5-ga, Sungbuk-gu, Seoul 136-705, Korea. ojr4991@korea.ac.kr
  • 2Department of Biomedical Sciences, Korea University, College of Medicine, Seoul, Korea.

Abstract

Spherical neural mass (SNM) is a mass of neural precursors that have been used to generate neuronal cells with advantages of long-term passaging capability with high yield, easy storage, and thawing. In this study, we differentiated neural retinal progenitor cells (RPCs) from human induced pluripotent stem cells (hiPSC)-derived SNMs. RPCs were differentiated from SNMs with a noggin/fibroblast growth factor-basic/Dickkopf-1/Insulin-like growth factor-1/fibroblast growth factor-9 protocol for three weeks. Human RPCs expressed eye field markers (Paired box 6) and early neural retinal markers (Ceh-10 homeodomain containing homolog), but did not photoreceptor marker (Opsin 1 short-wave-sensitive). Reverse transcription polymerase chain reaction revealed that early neural retinal markers (Mammalian achaete-scute complex homolog 1, mouse atonal homolog 5, neurogenic differentiation 1) and retinal fate markers (brain-specific homeobox/POU domain transcription factor 3B and recoverin) were upregulated, while the marker of retinal pigment epithelium (microphthalmia-associated transcription factor) only showed slight upregulation. Human RPCs were transplanted into mouse (adult 8 weeks old C57BL/6) retina. Cells transplanted into the mouse retina matured and expressed markers of mature retinal cells (Opsin 1 short-wave-sensitive) and human nuclei on immunohistochemistry three months after transplantation. Development of RPCs using SNMs may offer a fast and useful method for neural retinal cell differentiation.

Keyword

Human induced pluripotent stem cells; Retinal photoreceptor; Retinal progenitor cell; Spherical neural mass

MeSH Terms

Animals
Cell Differentiation
Humans*
Immunohistochemistry
Induced Pluripotent Stem Cells
Methods
Mice
Neurons
Photoreceptor Cells, Vertebrate
Polymerase Chain Reaction
Retina
Retinal Pigment Epithelium
Retinaldehyde*
Reverse Transcription
Stem Cells*
Transcription Factors
Up-Regulation
Retinaldehyde
Transcription Factors
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