scholarly journals Cell Therapy Replacement for Retinal and Optic Nerve Diseases: Cell Sources, Clinical Trials and Challenges

2021 ◽  
Author(s):  
Rosa M. Coco-Martin ◽  
Salvador Pastor-Idoate ◽  
Jose C. Pastor Jimeno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Optic Nerve ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Limbal Stem Cells ◽  
Term Survival ◽  
Cell Therapies ◽  
Optic Nerve Diseases ◽  
Cell Sources

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

scholarly journals Cell Replacement Therapy for Retinal and Optic Nerve Diseases: Cell Sources, Clinical Trials and Challenges

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 865
Author(s):  
Rosa M. Coco-Martin ◽  
Salvador Pastor-Idoate ◽  
Jose Carlos Pastor
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Optic Nerve ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Limbal Stem Cells ◽  
Term Survival ◽  
Cell Therapies ◽  
Optic Nerve Diseases ◽  
Cell Sources

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce a localized retinal detachment to perform the subretinal placement of the transplanted cell; (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

scholarly journals Integrated Colony Imaging, Analysis, and Selection Device for Regenerative Medicine

2016 ◽  
Vol 22 (2) ◽  
pp. 217-223 ◽  
Author(s):  
Edward Kwee ◽  
Edward E. Herderick ◽  
Thomas Adams ◽  
James Dunn ◽  
Robert Germanowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Cell Types ◽  
Automated Image Analysis ◽  
Adherent Cell ◽  
Imaging Analysis ◽  
Cell Therapies ◽  
Stem And Progenitor Cells ◽  
Cell Sources ◽  
Selection Of

Stem and progenitor cells derived from human tissues are being developed as cell sources for cell-based assays and therapies. However, tissue-derived stem and progenitor cells are heterogeneous. Differences in observed clones of stem cells likely reflect important aspects of the underlying state of the source cells, as well as future potency for cell therapies. This paper describes a colony analysis and picking device that provides quantitative analysis of heterogeneous cell populations and precise tools for cell picking for research or biomanufacturing applications. We describe an integrated robotic system that enables image acquisition and automated image analysis to be coupled with rapid automated selection of individual colonies in adherent cell cultures. Other automated systems have demonstrated feasibility with picking from semisolid media or off feeder layers. We demonstrate the capability to pick adherent bone-derived stem cells from tissue culture plastic. Cells are efficiently picked from a target site and transferred to a recipient well plate. Cells demonstrate viability and adherence and maintain biologic potential for surface markers CD73 and CD90 based on phase contrast and fluorescence imaging 6 days after transfer. Methods developed here can be applied to the study of other stem cell types and automated culture of cells.

Efficient Derivation of Basal Progenitor Cells from Human Pluripotent Stem Cells for Modeling Esophageal Development

2018 ◽  
Author(s):  
Yongchun Zhang ◽  
Ying Yang ◽  
Ming Jiang ◽  
Sarah Xuelian Huang ◽  
Munemasa Mori ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Basal Progenitor

An Overview on Promising Somatic Cell Sources Utilized for the Efficient Generation of Induced Pluripotent Stem Cells

2021 ◽  
Author(s):  
Arnab Ray ◽  
Jahnavy Madhukar Joshi ◽  
Pradeep Kumar Sundaravadivelu ◽  
Khyati Raina ◽  
Nibedita Lenka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Somatic Cell ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Efficient Generation ◽  
Cell Sources ◽  
Induced Pluripotent

scholarly journals A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takamasa Hirai ◽  
Ken Kono ◽  
Rumi Sawada ◽  
Takuya Kuroda ◽  
Satoshi Yasuda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Sensitive Detection ◽  
Quality And Safety

AbstractHighly sensitive detection of residual undifferentiated pluripotent stem cells is essential for the quality and safety of cell-processed therapeutic products derived from human induced pluripotent stem cells (hiPSCs). We previously reported the generation of an adenovirus (Ad) vector and adeno-associated virus vectors that possess a suicide gene, inducible Caspase 9 (iCasp9), which makes it possible to sensitively detect undifferentiated hiPSCs in cultures of hiPSC-derived cardiomyocytes. In this study, we investigated whether these vectors also allow for detection of undifferentiated hiPSCs in preparations of hiPSC-derived neural progenitor cells (hiPSC-NPCs), which have been expected to treat neurological disorders. To detect undifferentiated hiPSCs, the expression of pluripotent stem cell markers was determined by immunostaining and flow cytometry. Using immortalized NPCs as a model, the Ad vector was identified to be the most efficient among the vectors tested in detecting undifferentiated hiPSCs. Moreover, we found that the Ad vector killed most hiPSC-NPCs in an iCasp9-dependent manner, enabling flow cytometry to detect undifferentiated hiPSCs intermingled at a lower concentration (0.002%) than reported previously (0.1%). These data indicate that the Ad vector selectively eliminates hiPSC-NPCs, thus allowing for sensitive detection of hiPSCs. This cytotoxic viral vector could contribute to ensuring the quality and safety of hiPSCs-NPCs for therapeutic use.

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