The eye is the window of the mind, and the retina, as an important part of the eyeball, is not only a nutrient photoreceptor cell, but also has the function of regeneration and repair. It is like a photoreceptor designed for photographic imaging, when looking at something, the image of the object will pass through the refraction system and eventually fall onto the retina (Figure 1). If the retina is damaged or degenerated, it can lead to lifelong visual impairment.
Figure 1 Schematic diagram of retinal imaging principle (Source: Baidu pictures)
As a part of the central nervous system, the retina is mainly composed of pigment epithelial cells, optic cells, bipolar cells, ganglion cells, horizontal cells, cells without long process, internetulum cells and Müller cells (MG).
The regenerative capacity of the retina is poor in mammals, but it is effectively regenerated in some cold-blooded vertebrates such as salamanders and fish. In these vertebrates, MG has the ability to regenerate the retina by expressing genes common to mitosis advanced retinal stem cells and entering the cell cycle in response to external injury. The research, titled "Müller glia fused with adult stem cells undergo neural differentiation in human retinal models", published in The Lancet sub-journal eBio Medicine, ultimately determined that MG in mammals retains inherent stem cell characteristics. In other words, the retina can be regenerated artificially, and the study promises to be a potential regenerative therapy for the treatment of human retinal damage, providing new treatment strategies for visually impaired patients (Figure 2).
Figure 2 Research results (Source: eBio Medicine)
The research team first used organ cultures from the human retina and preparations of dissociated cells to examine cell fusion between human MG and adult stem cells, producing hybrid cells (Figure 3). Cell fusion was not common in humans, but it has been found in the liver, brain, and gastrointestinal tract in the past, and now they have found that cell fusion also occurs in the human retina.
Figure 3 Cell fusion between human MG and adult stem cells (Source: eBio Medicine)
Next, the researchers used a specially built microinjection system to inject hybrid cells into the retinal organoids. The eventual discovery that the mixed "fusion cells" can be successfully transplanted into tissues and differentiated into cells that are very similar to ganglion cells (ganglion cells are neurons that are critical for vision) demonstrate the regenerative potential of fusion cells and promise to be a promising stem cell-mediated regenerative therapy for the human retina (Figure 4).
Figure 4 Locations of different types of neurons on the cross-section of retinal organoids (Source: eBio Medicine)
Note: Red (ganglion); green (Müller glial)
The team concludes that this result suggests that fusing human retinal cells with adult stem cells could be a potential therapeutic strategy for treating retinal damage and visual impairment.
Stem cells are changing the "rules of regeneration" in humans
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Chinese scientists have induced human totem stem cells
From the above research, it is not difficult to see that stem cells are a type of multi-potential cells with self-replication ability, which can differentiate into a variety of functional cells. Stem cells act as "seed" cells, and functional cells obtained by differentiation can participate in cell replacement and tissue regeneration. Stem cell research, as a key development field at the forefront of medicine in recent years, has shown good development prospects and brought hope for the effective treatment of some difficult diseases.
Researchers from the Chinese Academy of Sciences and Shenzhen Huada Institute of Life Sciences and other institutions have cultivated human totem stem cells similar to the developmental state of a fertilized egg for 3 days through somatic cell induction. The relevant research results were published in the early morning of March 22 this year in the internationally renowned academic journal Nature (Figure 5). Compared to past pluripotent stem cells, these cells can differentiate into placental tissue and may develop into more mature types of body tissue. This is currently the "youngest" human cell cultured in vitro in the world, and it is another subversive breakthrough in the field of regenerative medicine after scientists successfully induced human pluripotent stem cells.
Figure 5 Research results (Source: Nature)
In this study, the team also sorted and injected induced totipotent stem cells into mice for further development, and then used BGI's single-cell sequencing technology for large-scale cell mapping analysis. Ultimately, the researchers determined that the experimentally obtained totipotent stem cells were highly similar to human 8-stage embryonic cells, demonstrating the totipotency of the cells. This provides a scientific basis for the future use of patients' own cells for organ culture and for their own organ transplantation and replacement.
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South China Biopower stem cell regenerative medicine field
In addition to the breakthrough at the research level, in 2021, Hunan Boai Kangmin Stem Cell Tissue Engineering Co., Ltd., a wholly-owned subsidiary of Nanhua Biologics, signed an agreement with Changsha Maternal and Child Health Hospital and Hunan Normal University to jointly build a "stem cell regenerative medicine and reproductive health" industry-university-research cooperation demonstration base, so that research and industrialization go hand in hand and better explore stem cell regeneration technology.
At present, the scientific research transformation platform of Nanhua Bio has formed a four-legged development trend. In addition to the "Stem Cell Regenerative Medicine and Reproductive Health" industry-university-research cooperation demonstration base, it also has the Hunan Clinical Research Center of the National Stem Cell Transformation Resource Bank, the National and Local Joint Engineering Laboratory for the Creation of Animal Polypeptide Drugs, and the South China Institute of Biomedicine of Hunan Province, which injects new impetus into the innovation of national stem cell regenerative medicine technology.
Focus on the health of the eyes, AI technology shines
Stem cell regeneration technology has brought new treatment methods and ideas to eye diseases, and artificial intelligence (AI) has played an important role in the diagnosis of eye diseases.
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Eagle Pupil Technology - "AI Medical First Stock"
Eagle Pupil Technology focuses on the retinal disease diagnosis market, and takes the lead in obtaining China's first fundus artificial intelligence-assisted diagnosis of three types of medical device certificates, making Eagle Pupil Technology in a market leader position. The AirdoAIFUNDUS series products created by Eagle Pupil Technology can be applied to high blood pressure retinopathy, retinal vein obstruction, macular degeneration, pathological myopia and retinal detachment (Table 1).
Table 1 Research status of Eagle Pupil Technology Products
Table Source:[5]
At present, Eagle Pupil Technology is developing five SaMD products, including gestational diabetic retinopathy, gestational hypertensive retinopathy, intracranial hypertension retinopathy related to papillary water retinopathy, etc., these independent products will further broaden the company's disease detection categories and serve the health diagnosis and risk assessment platform.
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Blue Book based on retinal AI assessment
In August 2020, Elken Group, together with the Joint Laboratory of Ophthalmology Big Data of the National Center for Comprehensive Utilization of Scientific and Technological Information Resources and Public Service, and Airdoc released the "Blue Book on the Health of Millions of People With Physical Examinations" based on retinal artificial intelligence assessment.
The application of artificial intelligence in the medical field is becoming more and more mature, Wei Wenbin shared with everyone in his speech: "Eye health is a very serious problem in China, with the aging of the population, and the rejuvenation of eye diseases and chronic diseases, eye health is becoming more and more important. Eye health is also an important part of the health of the whole body, hypertension, diabetes, etc. are closely related to eye health, through the eyes can see the health of the whole body, to see the degree of risk of cardiovascular and cerebrovascular diseases. With the application of artificial intelligence and informatics, early screening, early intervention and long-term supervision can be truly implemented, and personalized and precise health management can be achieved for different groups of people. ”
The report shows that people aged 40 and above need to pay more attention to fundus health, among which the detection rate of abnormal retinal vascular abnormalities, retinal arteriosclerosis, and macular cloth abnormalities has increased by leaps and bounds. In addition, the three high and one fat people also need to pay more attention to the health of the eyes.
With the help of deep learning artificial intelligence technology, the risk of cardiovascular disease in the population is assessed through retinal image, and the traditional physical examination mode change is driven by artificial intelligence, which truly realizes the health status assessment of millions of physical examination populations based on retinal artificial intelligence assessment.
Taken together, the study demonstrates that fusion between human MG cell cells and adult stem cells may be a potentially developed stem cell-mediated therapy for human retinal regeneration and can be used to treat visually impaired diseases, and this new finding also suggests that human MG glial cells can "reverse fate" and regain regenerative activity.
As the only tissue in the whole body that can directly observe blood vessels and nerves, the retina can observe not only fundus diseases, but also systemic vascular diseases, systemic neurological diseases, and other diseases. The development of retinal regeneration technology has undoubtedly brought good news to many patients with fundus diseases. It is expected that this research technology will make breakthroughs to benefit many patients.
Source: Nature, for academic communication only.
Written by | Guo Haijun
Typography | essay competition
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Resources:
[1] Bonilla-Pons S , Nakagawa S, Bahima EG, et al. Müller glia fused with adult stem cells undergo neural differentiation in human retinal models. EBioMedicine. 2022 Mar;77:103914. doi: 10.1016/j.ebiom.2022.103914. Epub 2022Mar 9. PMID: 35278743; PMCID: PMC8917309.
[2] Scientists used a newly created cell to "awaken" the regenerative capacity of the human retina
https://new.qq.com/omn/20220327/20220327A01EFP00.html
[3] Breakthrough in regenerative medicine Chinese scientists induced human totem stem cells
https://finance.eastmoney.com/a/202203232320255421.html
[4] Nanhua Biology, Changsha Maternal and Child, and Hunan Normal University have established industry-university-research cooperation to https://finance.eastmoney.com/a/202203092302354363.html in the field of stem cell regenerative medicine
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