Facile isolation and the characterization of human retinal stem cells

Coles, Brenda L.K.; Angénieux, Brigitte; Inoue, Tomoyuki; Rio‐Tsonis, Katia Del; Spence, Jason R.; McInnes, Roderick R.; Arsenijévic, Yvan; Kooy, Derek van der

doi:10.1073/pnas.0401596101

Cited by 359 publications

(368 citation statements)

References 22 publications

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“…When transplanted, RSCs incorporate into the neural retina and rescue vision in animal models (for more detail see Lamba et al [22] and Wallace [23]. As with RPCs, RSCs transplanted into the subretinal space of young mice survive, migrate, integrate, and differentiate into appropriate cell types, including photoreceptor cells [24]. In healthy adult recipients, however, transplanted RSCs preferentially express ganglion cell or glial markers rather than the photoreceptor cell type needed for replacement of the outer retina [25].…”

Section: Rscsmentioning

confidence: 99%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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Retinal degenerative disease has limited therapeutic options and the possibility of stem cell-mediated regenerative treatments is being actively explored for these blinding retinal conditions. The relative accessibility of this central nervous system tissue and the ability to visually monitor changes after transplantation make the retina and adjacent retinal pigment epithelium prime targets for pioneering stem cell therapeutics. Prior work conducted for several decades indicated the promise of cell transplantation for retinal disease, and new strategies that combine these established surgical approaches with stem cell-derived donor cells is ongoing. A variety of tissue-specific and pluripotent-derived donor cells are being advanced to replace lost or damaged retinal cells and/or to slow the disease processes by providing neuroprotective factors, with the ultimate aim of long-term improvement in visual function. Clinical trials are in the early stages, and data on safety and efficacy are widely anticipated. Positive outcomes from these stem cell-based clinical studies would radically change the way that blinding disorders are approached in the clinic.

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Section: Rscsmentioning

confidence: 99%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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“…[17][18][19]21 Three to 7 days after plating (AP), phase-bright tumor spheres resembling the classical neurospheres were detected in all of the cultures established from both differentiated and undifferentiated RBs. In the first 12 hr AP, disaggregated tumor cells remained in the single cell state in culture flasks (Fig.…”

Section: Selection and Expansion Of Rslcsmentioning

confidence: 99%

“…19,21 A detailed protocol is provided in online supplementary materials. Briefly, tissue fragments obtained from either human retinoblastoma (RB) tumors or xenograft tumors were washed, minced, digested with trypsin, dissociated and passed through a series of cell strainers.…”

Section: Tissue Collectionmentioning

confidence: 99%

“…Immunofluorescence was performed with protocols as described previousely. 21 In some cases, nuclei were counterstained with Hoechst 33342. Finally, staining was visualized by confocal microscope (LSM510, Carl Zeiss, Oberkochen, Germany).…”

Section: Immunocytochemistrymentioning

confidence: 99%

“…20 Recently, our research group successfully cultured stemlike cells from human RB lesions using the methods culturing BTSCs and RSCs. 19,21 Our previous data showed that these stemlike cells exhibited RSC properties in vitro including extensive proliferation, self-renewal and multipotency. 22 However, we did not know whether these retinal stem-like cells (RSLCs) were able to reproduce parental tumors in animal model.…”

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confidence: 99%

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Identification of tumorigenic retinal stem‐like cells in human solid retinoblastomas

Zhong

Peng

et al. 2007

Intl Journal of Cancer

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Retinoblastoma (RB) is the most common malignant tumor of the retina in human children. Although it has been hypothesized for a long time that RB derives from multipotent retinal stem cells (RSCs) or retinoblasts, the direct evidence that the presence of tumorigenic RSCs in RB tumors is still lacking. Some studies indicate that malignant tumors contain tumor stem cells similar to their normal tissue stem cell counterparts. With in vitro culture and differentiation method we demonstrate that tumorigenic retinal stem-like cells (RSLCs) indeed exist in RB lesions and that RB tumor-derived cultures encompass undifferentiated cells capable of extensive proliferation as clonal nonadherent neurospheres and can differentiate into different retinal cells in vitro. Interestingly, cultured cells expressed retinal development related genes including nestin, CD133, pax6, chx10 and Rx, and overexpressed Bmi-1, a gene required for self-renewal and proliferation of stem cells. Significantly, when these cultured cells were intraocularly transplanted into SCID mice, they gave rise to new tumors with histomorphological features and immunophenotypes similar to their parental primary RBs. The results show that RBs contain tumorigenic RSLCs that contribute to tumorigenesis. This study provides a new insight to investigate the histogenesis of RBs and establishes a model for other RB research. ' 2007 Wiley-Liss, Inc.Key words: retinoblastoma; tumor stem cell; retinal stem cell; tumorigenesis Retinoblastom (RB) is the most common malignant tumor of the retina in children and has become an excellent study model for cancer biology and molecular mechanism. [1][2][3][4][5][6] It is categorized into differentiated and undifferentiated types by the World Health Organization (WHO) classification according to the presence of rosettes and the degree of atypia. 2 Most of previous studies have been focusing on the cellular and molecular analysis of the bulk tumor mass to search cell origin of RB tumor and RB gene mutation. Although the origin of RB cells has been somewhat controversial, it has been generally agreed that RB cells originate from the multipotent primitive retinoblasts or retinal stem cells (RSCs). 3,[7][8][9][10][11][12][13][14][15][16] Up to date, there is no direct evidence to support that tumorigenic RSCs exist in RBs. In recent years, brain tumor stem cells (BTSCs) have been isolated from human brain malignant tumor samples and cultured then transplanted into experimental animals to form new tumors, providing strong evidence that these BTSCs are the origin of the brain tumor. [17][18][19] In 2005, Siegal et al. demonstrated that mouse and human RB cells contained a small subpopulation of cells exhibiting a cancer stem cell-like phenotype. 20 Recently, our research group successfully cultured stemlike cells from human RB lesions using the methods culturing BTSCs and RSCs. 19,21 Our previous data showed that these stemlike cells exhibited RSC properties in vitro including extensive proliferation, self-renewal and multipotency. 22 H...

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