Pigmented epithelium induces complete retinal reconstitution from dispersed embryonic chick retinae in reaggregation culture

Rothermel, Andrée; Willbold, Elmar; DeGrip, Willem J.; Layer, Paul G.

doi:10.1098/rspb.1997.0179

Cited by 58 publications

(53 citation statements)

References 39 publications

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“…On the other hand, the presence of organized photoreceptors in the transplant appeared to support the maintenance and maturation of the cotransplanted RPE sheet. Other studies have shown that the RPE is necessary for normal retinal morphogenesis in vivo (Raymond and Jackson, 1995) and in¯uences the lamination of neural retina in vitro by acting on early Mu È ller glial cells via diffusible factors (Rothermel et al, 1997).…”

Section: Donor Tissuementioning

confidence: 99%

Transplanted Sheets of Human Retina and Retinal Pigment Epithelium Develop Normally in Nude Rats

Aramant

Seiler

2002

Experimental Eye Research

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This study investigated whether transplanted sheets of human fetal retina together with its retinal pigment epithelium (RPE) could develop and maintain their cytoarchitecture after long survival times. Transplant recipients were nine albino athymic nu/nu rats with a normal retina. The donor tissue was dissected from fetuses of 12±17 weeks gestational age. Transplants were analyzed at 5±12 months after surgery by light and electron microscopy, and immunohistochemistry with various antibodies speci®c for rhodopsin, S-antigen, transducin, neuro®lament and synaptophysin. In 4 of 11 transplants, the RPE stayed as a monolayer sheet and supported the development of the retinal sheet with a normal lamination, including photoreceptor inner and outer segments. Cones and rods in the organized transplants were labeled with different photoreceptor markers. Inner and outer plexiform layers, containing cone pedicles and rods spherules, were immunoreactive for synaptophysin. As the recipients had a normal retina, transplant/host integration was not expected. However, at the transplant/host interface, there were sometimes areas without glial barriers, and neuro®lament-containing processes could be observed crossing between transplant and host. In other, more disorganized transplants, the RPE cells were partially dispersed or clumped together in clusters. Such transplants developed photoreceptors in rosettes, often with inner and outer segments.In conclusion, sheets of human fetal retina transplanted together with its RPE to the subretinal space of nude rats can develop and maintain perfectly laminated transplants after long survival times, indicating the potential of applying cotransplantation to human patients with retinal diseases.# 2002 Elsevier Science Ltd.

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Section: Donor Tissuementioning

confidence: 99%

Transplanted Sheets of Human Retina and Retinal Pigment Epithelium Develop Normally in Nude Rats

Aramant

Seiler

2002

Experimental Eye Research

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“…This indicates that during the early stages of neurogenesis, neighbouring tissues -at least in the case of the retina and cerebellum -secrete diffusible factors which are involved in the determination of the future inside-out polarity. With respect to the retina, pigmented epithelium-derived factors are the most potent inducers of a correct polarity in vitro (100%) [Rothermel et al, 1997], whereas Müller cell-derived [Willbold et al, 2000] and cerebellar glia cellderived factors are less inductive (80 and 50%, respectively). However, Müller cells (or their immature precursors) seem to be the primary candidates and the cellular substrate both for the targeted distribution of these factors and for the maintenance of the polarity.…”

Section: Is Induction Of Cell Column Polarity Under the Control Of Ramentioning

confidence: 99%

“…The general structure of rosetted spheroids is accomplished by additional 'nonorganized areas' which interconnect the laminated areas. Interestingly, the inverse polarity of rosetted spheroids can be completely corrected, provided the spheroids are cultured in conditioned media derived from monolayers of pigmented epithelial cells or Müller cells [Rothermel et al, 1997;Willbold et al, 2000]. Instead of forming a multicentric and inverse lamination pattern, all of the spheroid's cells undergo a complete reorientation.…”

Section: Introductionmentioning

confidence: 99%

“…Instead of forming a multicentric and inverse lamination pattern, all of the spheroid's cells undergo a complete reorientation. As a result, a correctly stratified and completely new spheroid type develops, the so-called stratified spheroids [Rothermel et al, 1997]. Because direct cell-to-cell contacts could be excluded, diffusible factors are responsible for the stratified spheroid-inducing effect.…”

Section: Introductionmentioning

confidence: 99%

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Cerebellar Glia Cells Induce a Correct Laminar Organization in Chicken Retinal Reaggregates

Willbold¹,

Rothermel²,

Huhn³

et al. 2001

Cells Tissues Organs

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We investigated the functional role of glia cells during retinogenesis using the rotation culture system. Reaggregating cells from the embryonic chick retina have the unique capacity to reassemble into laminated cellular spheres. These spheres are composed of several compartments holding the constituents of many retinal layers in a topologically correct, yet inverse orientation. However, when these spheres are cultured in the presence of conditioned media derived from monolayers of cerebellar glia cells, the reassembling retinal cells behave totally differently. The anlage of the originally reversed lamina polarity is progressively transformed within a week into a sphere with a compound and correctly laminated orientation. Conditioned media from fibroblasts, other glia cells (except Müller cells) or a set of already characterized retinogenetic factors are not able to produce this dramatic transformation. Additionally, we were able to show that only retinal cells are able to respond with a reorganization process. Reaggregating cells from the chick cerebellum also form spheroids; however, neither in the presence of cerebellar glia cell-derived conditioned medium nor their control counterparts are they able to reassemble histotypically. This indicates that cerebellar glia cells produce diffusible factors to which retinal cells can respond and that these factors can act as important determinants for the correct establishment of the retinal polarity. Since all types of laminar disorganization are of great clinical significance, the knowledge of factors which determine and sustain the normal retinal architecture are biomedically highly relevant.

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“…A plethora of experiments in chick embryos has documented that retina have a remarkable capacity to reconstitute different types of spheres with almost complete arrangement of retinal layers [46,47], and, as in other organoid approaches, this laid the groundwork for the development of PSC-derived retinal organoids.…”

Section: Retinal Organoidsmentioning

confidence: 99%

Organoid Models and Applications in Biomedical Research

Xinaris

Brizi

Remuzzi

2015

Nephron

2,386

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Recent technical advances in the stem cell field have enabled the in vitro generation of complex structures resembling whole organs termed organoids. Most of these approaches employ three-dimensional (3D) culture systems that allow stem cell-derived or tissue progenitor cells to self-organize into 3D structures. These systems evolved, methodologically and conceptually, from classical reaggregation experiments, showing that dissociated cells from embryonic organs can reaggregate and re-create the original organ architecture. Since organoids can be grown from human stem cells and from patient-derived induced pluripotent stem cells, they create significant prospects for modelling development and diseases, for toxicology and drug discovery studies, and in the field of regenerative medicine. Here, we outline historical advances in the field and describe some of the major recent developments in 3D human organoid formation. Finally, we underline current limitations and highlight examples of how organoid technology can be applied in biomedical research.

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Pigmented epithelium induces complete retinal reconstitution from dispersed embryonic chick retinae in reaggregation culture

Cited by 58 publications

References 39 publications

Transplanted Sheets of Human Retina and Retinal Pigment Epithelium Develop Normally in Nude Rats

Transplanted Sheets of Human Retina and Retinal Pigment Epithelium Develop Normally in Nude Rats

Cerebellar Glia Cells Induce a Correct Laminar Organization in Chicken Retinal Reaggregates

Organoid Models and Applications in Biomedical Research

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