scholarly journals Sox2, Tlx, Gli3, and Her9 converge on Rx2 to define retinal stem cells in vivo

2015 ◽  
Vol 34 (11) ◽  
pp. 1572-1588 ◽  
Author(s):  
Robert Reinhardt ◽  
Lázaro Centanin ◽  
Tinatini Tavhelidse ◽  
Daigo Inoue ◽  
Beate Wittbrodt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinal Stem Cells

scholarly journals Activation of adult mammalian retinal stem cells in vivo via antagonism of BMP and sFRP2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kenneth N. Grisé ◽  
Brenda L. K. Coles ◽  
Nelson X. Bautista ◽  
Derek van der Kooy
Keyword(s):  
Stem Cells ◽  
Retinal Degeneration ◽  
Vision Loss ◽  
Lineage Tracing ◽  
Retinal Cell ◽  
Ciliary Epithelium ◽  
Genetic Lineage ◽  
Quiescent State ◽  
Retinal Stem Cells

Abstract Background The adult mammalian retina does not have the capacity to regenerate cells lost due to damage or disease. Therefore, retinal injuries and blinding diseases result in irreversible vision loss. However, retinal stem cells (RSCs), which participate in retinogenesis during development, persist in a quiescent state in the ciliary epithelium (CE) of the adult mammalian eye. Moreover, RSCs retain the ability to generate all retinal cell types when cultured in vitro, including photoreceptors. Therefore, it may be possible to activate endogenous RSCs to induce retinal neurogenesis in vivo and restore vision in the adult mammalian eye. Methods To investigate if endogenous RSCs can be activated, we performed combinatorial intravitreal injections of antagonists to BMP and sFRP2 proteins (two proposed mediators of RSC quiescence in vivo), with or without growth factors FGF and Insulin. We also investigated the effects of chemically-induced N-methyl-N-Nitrosourea (MNU) retinal degeneration on RSC activation, both alone and in combination withthe injected factors. Further, we employed inducible Msx1-CreERT2 genetic lineage labeling of the CE followed by stimulation paradigms to determine if activated endogenous RSCs could migrate into the retina and differentiate into retinal neurons. Results We found that in vivo antagonism of BMP and sFRP2 proteins induced CE cells in the RSC niche to proliferate and expanded the RSC population. BMP and sFRP2 antagonism also enhanced CE cell proliferation in response to exogenous growth factor stimulation and MNU-induced retinal degeneration. Furthermore, Msx1-CreERT2 genetic lineage tracing revealed that CE cells migrated into the retina following stimulation and/or injury, where they expressed markers of mature photoreceptors and retinal ganglion cells. Conclusions Together, these results indicate that endogenous adult mammalian RSCs may have latent regenerative potential that can be activated by modulating the RSC niche and hold promise as a means for endogenous retinal cell therapy to repair the retina and improve vision.

scholarly journals Bipotent progenitors as embryonic origin of retinal stem cells

2017 ◽  
Vol 216 (6) ◽  
pp. 1833-1847 ◽  
Author(s):  
Xia Tang ◽  
Jianan Gao ◽  
Xinling Jia ◽  
Wencao Zhao ◽  
Yijie Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Types ◽  
Tissue Growth ◽  
Retinal Cell ◽  
Lower Vertebrates ◽  
Embryonic Origin ◽  
Optic Vesicles ◽  
Lineage Analysis ◽  
Retinal Stem Cells

In lower vertebrates, retinal stem cells (RSCs) capable of producing all retinal cell types are a resource for retinal tissue growth throughout life. However, the embryonic origin of RSCs remains largely elusive. Using a Zebrabow-based clonal analysis, we characterized the RSC niche in the ciliary marginal zone of zebrafish retina and illustrate that blood vessels associated with RSCs are required for the maintenance of actively proliferating RSCs. Full lineage analysis of RSC progenitors reveals lineage patterns of RSC production. Moreover, in vivo lineage analysis demonstrates that these RSC progenitors are the direct descendants of a set of bipotent progenitors in the medial epithelial layer of developing optic vesicles, suggesting the involvement of the mixed-lineage states in the RSC lineage specification.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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