scholarly journals Human embryonic stem cells-derived dopaminergic neurons transplanted in parkinsonian monkeys recover dopamine levels and motor behavior

2020 ◽  
Author(s):  
Adolfo López-Ornelas ◽  
Itzel Escobedo-Avila ◽  
Gabriel Ramírez-García ◽  
Rolando Lara-Rodarte ◽  
César Meléndez-Ramírez ◽  
...  

Human embryonic stem cells (hESCs) differentiate into specialized cells, including midbrain dopaminergic neurons (DAN). Non-human primates (NHPs) injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine develop some alterations observed in Parkinson’s disease (PD) patients. We obtained DAN from hESCs and confirmed that they express dopaminergic markers, generate action potentials, and release dopamine (DA) in vitro. DAN were transplanted bilaterally in the putamen of parkinsonian NHPs. After grafting, animals improved motor behavior, evaluated by the HALLWAY task, and in agreement with this recovery, DA release was detected by microdialysis. Imaging techniques revealed changes in fractional anisotropy and mean diffusivity in magnetic resonance imaging and higher 11C-DTBZ binding in positron-emission tomography scans, associated with grafts. Postmortem analysis showed that transplanted DAN survived over ten months in the putamen, without developing tumors, in the immunosuppressed NHPs. These results indicate that cell replacement therapy with hESCs-derived DAN causes long-term biochemical, anatomical, and physiological improvements in this model of PD.

2004 ◽  
Vol 359 (1-2) ◽  
pp. 99-103 ◽  
Author(s):  
Sepill Park ◽  
Keum Sil Lee ◽  
Young Jae Lee ◽  
Hyun Ah Shin ◽  
Hwang Yoon Cho ◽  
...  

Author(s):  
Eun-Young Shin ◽  
Seah Park ◽  
Won Yun Choi ◽  
Dong Ryul Lee

Abstract Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.


2013 ◽  
Vol 14 (12) ◽  
pp. 4207-4216 ◽  
Author(s):  
Matthew Leung ◽  
Ashleigh Cooper ◽  
Soumen Jana ◽  
Ching-Ting Tsao ◽  
Timothy A. Petrie ◽  
...  

2010 ◽  
Vol 6 (2) ◽  
pp. 237-247 ◽  
Author(s):  
Elaine Vo ◽  
Donny Hanjaya-Putra ◽  
Yuanting Zha ◽  
Sravanti Kusuma ◽  
Sharon Gerecht

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