Cell therapy is promising in treating psychiatric disorders, such as depression. -- A proof-of-principle study published in "Cell Stem Cell" by the laboratory of Dr. Chen, founder of UniXell Biotech, suggests this.

Wed, 20 Aug 2025 20:49:00 +0800

SHANGHAI, Aug. 20, 2025 /PRNewswire/ -- On August 11, 2025, the research team led by Professor Yuejun Chen, founder of UniXell Biotech, published an article titled "Human stem cell-derived A10 dopaminergic neurons specifically integrate into mouse circuits and improve depression-like behaviors" in Cell Stem Cell, featured as a cover story. This study marks the first establishment of a technique to efficiently and directionally differentiate human pluripotent stem cells (hPSCs) into A10 subtype dopamine neurons. This breakthrough lays a critical scientific foundation for cell therapy of psychiatric disorders such as depression.

In this study, the R&D team of UniXell Biotechnology played a crucial role in manuscript preparation/cell differentiation, transplantation, and immunohistochemistry analysis/cell line establishment, driving the entire process from proof-of-concept to publication and providing key support for the high-quality presentation of the research outcomes. 

Depression is one of the most common mental disorders in the 21^st century, projected to become one of the top three causes of global disease burden by 2030. Despite the widespread clinical use of existing antidepressant drugs, approximately one-third of patients suffer from treatment-resistant depression (TRD), showing poor response to current pharmacotherapies. The fundamental symptoms exhibited by depression patients, such as anhedonia and anxiety disorders, are closely associated with the regulatory network of A10 dopaminergic neuron subtypes.

The authors found that whether hPSC-derived A10 dopaminergic neurons were transplanted into the mouse VTA (orthotopic transplantation) or the nucleus accumbens (heterotopic transplantation), the grafted cells could accurately project to the target brain regions of endogenous A10 subtype dopaminergic neurons and specifically integrate into the host neural circuits. This result demonstrates that A10 dopaminergic neurons possess remarkable subtype specificity and precise neural circuit integration capabilities.

When chemogenetically engineered transplanted A10 dopaminergic neurons were activated by specific ligands, the host mice exhibited significant anti-anxiety and anti-depression phenotypes in behavioral experiments. This study is the first to demonstrate that transplantation of hPSC-derived A10 dopaminergic neuron subtypes can reconstruct this neural circuit and improve behavioral abnormalities in modeled mice, providing a novel approach for cell therapy in psychiatric disorders.

"This represents a milestone in the relatively unexplored field of cell therapy for mental illnesses. The study will initiate the clinical translation of using A10 dopaminergic neurons for depression at UniXell, which I believe will establish UniXell as a leading biotech in the field of cell therapy for psychiatric disorders," said Dr. Chen.

About UniXell Biotechnology

Shanghai UniXell Biotechnology Co., Ltd. was established in 2021, focusing on cell therapy drug development for neurological diseases such as Parkinson's disease and epilepsy. The company possesses a 4,000-square-meter R&D center and GMP facility, and has developed four innovative technology platforms based on reprogramming technology, stem cell differentiation technology, SISBAR lineage tracing technology, and high-precision gene editing. By 2025, the company has filed over 20 patent applications, with 4 granted utility model patents and 6 software copyrights. Its self-developed cell therapy drugs have received IND approvals from both China's National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA). Two subjects have successfully dosed, with postoperative data indicating good recovery.