Recommended reading:
1. Overview of the research progress of ips cell treatment of diabetes in 2020
2. Experimental materials related to iPS cell reprogramming experiment
Comparison of various cell reprogramming techniques
IPS: Cell reprogramming technology cleverly circumvents the ethical dilemma of embryonic stem cells "killing to save people" and is considered to have broad prospects for medical applications. A variety of body tissues can be obtained with iPS cells-even better, these cells can be the patient's own, and there is no need to consider the potentially fatal effects of cells or organs from other people. However, iPS cells have been shown to have their own epigenetic imprints and telomere abnormalities. Compared with embryonic stem cells, hundreds of genes are abnormally expressed in iPS cells, which are teratomogenic, and retain the initial cells. Memory", subsequent studies have shown that even autologous iPS differentiated cells can cause immune rejection. The iPS induction efficiency is low, the in vitro operation process is complicated and lengthy, which constitutes a great uncertainty for the genetic stability, epigenetic characteristics and biological characteristics of the cells, and the chance of cell decline or malignant transformation is greatly increased.
Direct transdifferentiation : Compared with iPS, direct transdifferentiation technology reduces the complexity of in vitro operations, and to a considerable extent avoids the risk of steps required to regress to a pluripotent state, such as tumorigenesis. However, the direct transdifferentiation technology is not a universal platform, it can only convert between cells of a specific lineage, and the efficiency is low; the expansion capacity of mature cells is limited, and it is difficult to obtain enough cells for clinical purposes, which affects this technology. The value of clinical application.
Indirect lineage conversion: Unlike iPS and direct transdifferentiation, indirect lineage conversion uses partial reprogramming techniques to shortly push mature cells back to a malleable intermediate state, and then differentiate. The researchers used this method to successfully convert human fibroblasts into mesoderm progenitor cells, which can differentiate into endothelial cells and smooth muscle cells.
Compared with iPS cell technology, indirect lineage switching shortens or bypasses the complete process of reprogramming to pluripotency, providing a simple and efficient technology, shortening the in vitro process from nearly two months to two weeks, and reducing the occurrence of mutations and The risk of teratoma. Compared with direct transdifferentiation technology, indirect lineage conversion provides a more general platform strategy, which can generate stem cells with cross-lineage differentiation ability faster. Stem cells can be expanded in vitro on a large scale, which is expected to satisfy the type and quantity Required for future clinical applications.
In short, whether it is direct transdifferentiation or indirect lineage conversion, they are still only "variants" of cell reprogramming technology, facing many common problems, such as: cell morphological and functional integrity, degree of epigenetic variation, gene integrity, Granules and telomerase, source cell memory, immunogenicity, and screening of clinical standard cells, etc., all reprogramming technologies must be tested by these practical standards and will ultimately determine their clinical application value.
There is no forbidden zone in scientific exploration, but the goal path and value orientation of applied technology and science are very different. Before stem cell technology is used in clinical applications, in addition to solving quantitative, effective, and ethical issues, it must also meet the needs of quality controllability and safety, and pass the necessary technical and economic feasibility assessment. From this point of view, adult stem cells derived from perinatal tissue, bone marrow, and fat are closer to the conditions for clinical applications than reprogramming technology . In addition, the natural "sub-totipotent stem cells" obtained from adult tissues with the ability to differentiate into three germ layers and multiple lineages may also pose a challenge to the ascending cell reprogramming technology.