scholarly journals Human primitive mesenchymal stem cell-derived retinal progenitor cells promoted neuroprotection and neurogenesis in rd12 mice

2021 ◽  
Author(s):  
Christina Brown ◽  
Patrina Agosta ◽  
Christina McKee ◽  
Keegan Walker ◽  
Matteo Mazzella ◽  
...  

Retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP) have no treatment. Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. We investigated a novel approach in which human retinal progenitor cells (RPCs) derived from primitive mesenchymal stem cells (pMSCs) were examined to treat retinal degeneration in an rd12 mouse model of RP. Intravitreally transplanted cells improved retinal function and significantly increased retinal thickness. Transplanted cells homed, survived, and integrated to various retinal layers. They also induced anti-inflammatory and neuroprotective responses and upregulated neurogenesis genes. We found that RPCs were more efficacious than pMSCs in improving the retinal structure and function. RNA analyses suggest that RPCs promote neuroprotection and neuronal differentiation by activating JAK/STAT and MAPK, and inhibiting BMP signaling pathways. These promising results provide the basis for clinical studies to treat RDD using RPCs derived from pMSCs.

2006 ◽  
Vol 23 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Brenda L. K. Coles ◽  
D. Jonathan Horsford ◽  
Roderick R. McInnes ◽  
Derek Kooy

2021 ◽  
Author(s):  
Xi Chen ◽  
Shanshan Li ◽  
Xiaoli Liu ◽  
Jingjie Zhao ◽  
Xiufen Yang ◽  
...  

Abstract Background c-Kit/CD117, expressed in a series of tissue-specific progenitor cells, plays an important role in tissue regeneration and tissue homeostasis. We previously demonstrated that organoid-derived c-Kit+ retinal progenitor cells can facilitate the restoration of degenerated retina. Meanwhile, we have identified a population of endogenous c-Kit+ cells in retinas of adult mouse. However, the exact role of these cells in retinal degeneration remains unclear. Methods Retinal degeneration was induced by intravitreal injection of N-methyl-D-aspartate (NMDA). Two days post NMDA challenge, intravitreal injection of stem cell factor (SCF) was performed. Distribution and abundance of c-Kit+ cells and other retinal cells were evaluated by immunochemistry. Retinal function of treated mice was tested via flash electroretinogram (fERG) and the light/dark transition test. Possible regulatory pathways were evaluated by RNA sequencing. Results NMDA challenge increased the total number of c-Kit+ cells in the retinal ganglion cell layer (GCL), while slightly deregulated the protein level of SCF, which is mainly expressed in Müller cells. Both fERG and light/dark transition tests showed that intravitreal injection of SCF effectively improve the visual function of NMDA-treated mice. Consistently, the activation of microglia in injured retina has also been inhibited after SCF treatment. Mechanistically, SCF administration not only prevent the loss of retinal ganglion cells (RGCs), but also maintained the function of RGCs as quantified by fERG. Further, we performed transcriptome sequencing analysis of the retinal cells isolated from SCF-treated mice and the parallel control. Gene Ontology analysis showed that SCF-induced transcriptome changes were closely correlated with eye development-related pathways. Crystallins and several protective factors such as Pitx3 were significantly upregulated by SCF treatment. Conclusions Our results revealed the role of c-Kit+ cells in the protection of RGCs in NMDA-treated mice, via inhibiting the loss of RGCs. Administration of SCF can act as a potent strategy for treating retinal degeneration-related diseases.


2003 ◽  
Vol 341 (3) ◽  
pp. 213-216 ◽  
Author(s):  
Tadamichi Akagi ◽  
Masatoshi Haruta ◽  
Joe Akita ◽  
Akihiro Nishida ◽  
Yoshihito Honda ◽  
...  

2021 ◽  
Vol 62 (3) ◽  
pp. 31
Author(s):  
Lorena Teixeira Frasson ◽  
Barbara Dalmaso ◽  
Priscilla Sayami Akamine ◽  
Edna Teruko Kimura ◽  
Dânia Emi Hamassaki ◽  
...  

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