Int J Stem Cells.  2024 Aug;17(3):224-235. 10.15283/ijsc23091.

Human Endometrial Regenerative Cells for Neurological Disorders: Hype or Hope?

• Momeni J
• Naserzadeh E
• Sepehrinezhad A
• Ahmadabad RA
• Negah SS

• KMID: 2558602
• DOI: http://doi.org/10.15283/ijsc23091

Abstract

Despite enormous efforts, no effective medication has been found to significantly halt or even slow the progression of neurological diseases, such as acquired (e.g., traumatic brain injury, spinal cord injury, etc.) and chronic (e.g., Parkinson’s disease, Alzheimer’s disease, etc.) central nervous system disorders. So, researchers are looking for alternative therapeutic modalities to manage the disease’s symptoms and stop it from worsening. Concerning disease-modifying capabilities, stem cell therapy has emerged as an expanding domain. Among different types of stem cells, human endometrial regenerative cells have excellent regenerative properties, making them suitable for regenerative medicine. They have the potential for self-renewal and differentiation into three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells (MSCs). ERCs can be isolated from endometrial biopsy and menstrual blood samples. However, there is no comprehensive evidence on the effects of ERCs on neurological disorders. Hence, we initially explore the traits of these specific stem cells in this analysis, followed by an emphasis on their therapeutic potential in treating neurological disorders.

Keyword

Stem cell transplantation; Central nervous system diseases; Endometrium; Regenerative medicine

Figure

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  Fig. 1 Schematic diagram of isolation, characterization, and differentiation capacity of human endometrial regenerative cells (ERCs). Human ERCs can be collected from the uterus using an endometrial biopsy device and menstrual silicon cups. ERCs comprise three types of stem cells: epithelial stem cells, endothelial side population stem cells, and mesenchymal stem cells. ERCs have the ability to differentiate into various neural lineages. Created with BioRender.com.

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  Fig. 2 Mechanisms of probable therapeutic effects of human endometrial regenerative cells (hERCs) in a traumatic brain injury model. hERCs can alleviate detrimental effects of brain injury through several important pathways; 1. Increasing the expression of neurotrophic factors, such as nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 for triggering the neurogenesis; 2. Improving the volume of lesion cavity; 3. Decreasing the expression levels of proinflammatory cytokines in the brain tissue and prevention of neuroinflammation; 4. Reducing the expression of proapoptotic genes, such as Bad and Bax; 5. Increasing nerve regeneration and improving the axonal remyelination; 6. Decreasing the leukocytes infiltration following inflammatory condition; 7. Suppressing the main inflammatory cytokines and reactive oxygen species (ROS); 8. Restoring the reactive glial cells and controlling vasogenic and cytotoxic edema with reduction of proinflammatory cytokines and ROS; 9. Inducing the formation of micro vessels. BBB: blood-brain barrier, IL-1β: interleukin 1 beta, IL-6: interleukin 6, TNFα: tumor necrosis factor α, COX2: cyclooxygenase 2, iNOS: inducible nitric oxide synthase.

Reference

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