What is Neuromuscular Reprogramming?

Nuclear reprogramming refers to the change in gene expression within a cell from one type to another. Earlier research on frog cloning provided preliminary experimental evidence for reprogramming, and later evidence included somatic cell nuclear transfer, cell fusion, foreign gene-induced reprogramming, and direct reprogramming.

Nuclear reprogramming

With this technique, the more easily available cell types (such as skin cells) can be transformed into another more difficult type (such as brain cells) on the same individual. The realization of this technology will prevent immune rejection from allogeneic transplantation. ^[1]

During the development of a fertilized egg into a mature individual, certain types of cells are generally formed along "one-way streets". As development continues, these cells will gradually lose their plasticity and become a particular type of cell that is irreversible. For example, a skin cell does not automatically turn into a brain cell, and a small intestine cell does not turn into a heart cell. However, there are some experimental methods that make it possible to switch between different cell types. These methods use the principle of nuclear reprogramming, that is, the transformation of nuclear gene expression in one type of cell into the state of embryonic cells or other types of cells. This mechanism has aroused widespread interest in the scientific community.

The "natural cross-linking theory of biological molecules" of aging states that the root cause of biological growth, development, and aging is the proliferation and differentiation of cells, which is a progressive molecular cross-linking caused by the interaction of chemically active groups in various biological macromolecules. This theory points out that when demonstrating the molecular mechanism of organism aging: the organism is an unstable chemical system and belongs to a dissipative structure. Various biomolecules in the system have a large number of active groups, and they must interact with each other to cause chemical reactions to slowly crosslink the biomolecules to stabilize the chemical activity. Over time, the degree of cross-linking continues to increase, the active groups of biomolecules are continuously consumed and the original molecular structure is gradually changed. The accumulation of these changes will gradually cause the aging of biological tissues.

The division and proliferation of an aging cell have stopped, and most of the DNA and other biomolecules are in a cross-linked state. The cross-linking reaction of biomolecules balances with a more aging direction in which the active molecules are decreasing; however, if aging Cells can re-enter the orbit of division and proliferation or otherwise make the rate of active biomolecules significantly faster than the rate of cross-linking inactivation, which can break the ever-decreasing aging balance of such active molecules and restore the cells to a younger age Even almighty.

Will the mechanisms between nuclear transfer, iPS technology, and transdifferentiation be the same? Maybe not. The concept of fast escape may be applicable to the above cases, but the factors that play a role in reprogramming are not the same. We already know that egg cells have certain very high concentrations of molecules, such as nuclear plasma, histone B4, and histone H3.3. The identification of egg reprogramming factors will help improve the efficiency of iPS and find more ways to switch between adult cells.

A person has 10 ^ 15 power cells, while a liver contains 10 ^ 14 power cells. To achieve this number, an iPS cell produced from the skin with an efficiency of 10 ^ 4 requires a large number of cell division cycles to reach. Nevertheless, some tissues of the human body require only a relatively small number of cells to improve function. One example is the retina, where only 105 cells have a therapeutic effect.

If the introduced cells are not "integrated" into the recipient, will these cells still be useful? Most tissues are made up of many different cell types. Taking the pancreas as an example, it contains at least four endocrine cells that can secrete hormones, including exocrine cells, ductal cells, and islet cells. The replacement therapy of endocrine cells has great therapeutic value, even if they are not integrated into the complex structure of the pancreas. In some cases, the introduced cells can provide functional convenience even in an indirect form. It is unclear whether the introduced cells can provide the right amount of product.

Looking ahead, more cell replacement therapies may emerge. One possibility is to find small molecules that can enter the cell to replace foreign genes into the cell, or may find more and more naturally dividing cell populations in adult organs, and these cells can be cultured and expanded in vitro Increase, and then used for transplantation. Future research directions, at least in our opinion, should be focused on the research of "single pluripotency" or "oligopluripotency" (which can only produce one or several cell types), even if it is not pluripotency ( The ability to differentiate into three germ cells) should never be totipotent (the ability to differentiate into all embryonic and extraembryonic cell types) (Figure 5). By analogy, we are more willing to achieve a desired cell type by converting a normal cell that is close to the desired cell type, rather than first transforming the cell into a totipotent state and then slowly moving from a large Scope to narrow their path of differentiation. If it is only for the purpose of cell replacement therapy, neither totipotency nor germline transmission ability is the required standard or goal. If only from the perspective of treatment, one has a certain differentiation ability, but this state of differentiation ability is not unlimited and may be safer and more effective.

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