Written by: Yang, Fujian Medical University
Expert review: Professor Li Jing, Affiliated Hospital of Jiangsu University
According to the previously released application guidelines (draft for comment), the 2022 annual guidelines are deployed around five key tasks, including the regulation and mechanism of stem cell fate, the occurrence and aging of stem cells and organs, the in situ regeneration of organs and their mechanisms, complex organ manufacturing and functional remodeling, and stem cell-based disease models. Among them, the research of intervention technology for stem cell and organ aging is one of the key directions.
Today we will take a look at what progress has been made in stem cell technology for intervening in aging and organ repair?
New means of intervening in aging are imminent
Man is inherently dead, and aging is a stage in the process of life, and all living things obey this natural law. According to WHO statistics[1], the world's elderly population aged 60 and over in 2019 was 1 billion. This figure will increase to 1.4 billion by 2030 and to 2.1 billion by 2050. Aging is so fast, there is a growing desire to delay aging and age healthily. Therefore, it is imperative to find new means of intervening in aging!
Aging manifests itself as structural changes and decreased function. Among them, the reduction of regenerative repair ability is the main feature of aging. With age, the aging of various cells in human tissues is the main reason for the decline of the body's regenerative repair ability.
In research, mechanisms such as the differentiation ability of stem cells and the paracrine effect are often used to exert anti-aging effects. In addition, aging often means the reduction of adult stem cells, the imbalance of stem cell function, if the vitality of adult stem cells is restored through stem cell transplantation, this is also a common means of anti-aging research.
In recent years, mesenchymal stem cells have made many achievements in the treatment of aging-related diseases, including tumors, type 2 diabetes, cardiovascular diseases and neurodegenerative diseases.
Stem cells intervene in aging through a variety of pathways
Studies have found that stem cells help the body fight aging through a variety of mechanisms:
Image from literature[2]
1. Regenerative repair function, stem cells proliferate and differentiate into different functional cells to replace aging and damaged cells, maintain the complete structure and normal function of tissues and organs.
2. Microenvironment regulator, stem cells can secrete a variety of biologically active proteins, including growth factors, cytokines, etc., and provide biological information to different cells in tissues and organs through the intercellular signal transduction system. For example, mesenchymal stem cells (MSCs) can secrete endothelial growth factors, initiate microvessel endothelial progenitor cell proliferation and microvessel regeneration; MSCs can also secrete cytokines that regulate immune function.
Research and application of stem cell technology in the field of skin anti-aging
The appearance of human organs changes with age, the most obvious of which is facial aging. Nowadays, not only women, but also many men are very concerned about their appearance changes, and the era of everyone's love of beauty has arrived. Facial aging is a complex process that affects both the shape of the face and facial textures such as dryness, roughness, dullness, and wrinkles.
Image from literature[3]
In recent years, scientists have made certain breakthroughs in the study of anti-skin aging using stem cells and their derivatives. Basic studies [3] show that MSCs can play a role in activating dermal fibroblast (HDF) proliferation, synthesizing collagen, reducing matrix metalloproteinases (MMPs), and antioxidant stress in UV-induced skin aging.
A clinical trial[4] injected adipose stem cell conditioned medium (ASC-CM) and placental stem cell conditioned medium (PSC-CM) into the facial skin, which showed that it greatly improved facial conditions such as erythema and melanin. After the detection of the conditioned medium components, it was found that it contained transforming growth factor -β, platelet-derived growth factor, fibroblast growth factor and angiogenesis vascular endothelial growth factor, which have important functional significance in skin remodeling and regeneration.
Stem cells are slowly breaking through the problem of organ reconstruction
All tissues and organs of the human body have a certain tolerance for diseases, but when the disease strikes more than the human body can withstand, it will cause irreversible damage to tissues and organs, and eventually even lead to death. The killer technique for the treatment of organ tissue failure is organ transplantation, but organ transplantation faces problems such as donor shortage, high cost and lifelong need for immune rejection. At present, tissue engineering is an emerging discipline that combines cell biology and materials science for the construction of tissues or organs in vitro or in vivo, which is expected to solve many problems in organ reconstruction.
Currently, stem cells are the best seed cells for tissue engineering because of their ability to proliferate and differentiate in vitro. For example, stem cells induce differentiation into nerve cells in vitro, which can be used as constituent cells of nerve fibers in tissue engineering. The liver cells derived from stem cells can become seed cells of "mini livers". In addition, with the development of biomaterials, stem cells, and tissue microarray technologies, humans will create "real organs" of the human body in vitro and provide patients with tissue-engineered organs for replacement, such as tissue-engineered skin and blood vessels [2].
Image from literature[5]
At present, the use of stem cell-based tissue engineering has been reconstructed in vitro to reproduce the bionic ear, islets, bone and cartilage, etc., and preliminary animal and clinical trials have been carried out. A study conducted by mainland scholars [5] combined 3D printing technology with cell culture technology to reconstruct a "new ear" in vitro, which was then transplanted into five children with congenital microtia and performed ear reconstruction. The "new ear" is highly similar to the other ear in terms of appearance and performance, greatly improving the appearance of these children.
prospect:
Cell therapy is undoubtedly one of the hot spots today, the use of stem cells, can help the body restore the function and vitality of organs. After a period of development, stem cell anti-aging is no longer a general concept, and has developed to the intervention stage of stem cells for aging-related diseases, such as the efficacy of stem cells on Alzheimer's disease, the therapeutic effect of stem cells on cataracts, etc. Although the realization of "immortality" needs to be further explored, a series of studies on stem cells and aging-related diseases have revealed positive signals that in the near future, we can achieve "healthy" aging without suffering from diseases!
bibliography:
[1]https://www.who.int/health-topics/ageing#tab=tab_1
[2] Yu Y. Application of Stem Cell Technology in Antiaging and Aging-Related Diseases. Adv Exp Med Biol. 2018;1086:255-265.
https://pubmed.ncbi.nlm.nih.gov/30232764/
[3] Gentile P, Garcovich S. Adipose-Derived Mesenchymal Stem Cells (AD-MSCs) against Ultraviolet (UV) Radiation Effects and the Skin Photoaging. Biomedicines. 2021;9(5):532. Published 2021 May 11.
https://pubmed.ncbi.nlm.nih.gov/34064624/
[4] Gaur M, Dobke M, Lunyak VV. Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging. Int J Mol Sci. 2017;18(1):208. Published 2017 Jan 20.
https://pubmed.ncbi.nlm.nih.gov/28117680/
[5] Zhou G, Jiang H, Yin Z, et al. In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction. EBioMedicine. 2018;28:287-302.
https://pubmed.ncbi.nlm.nih.gov/29396297/
[6] Shaim H, Shanley M, Basar R, et al. Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells. J Clin Invest. 2021;131(14):e142116.
https://pubmed.ncbi.nlm.nih.gov/34138753/
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