The Human Body Life Relies on the Cells: A Speech at the Satellite Meeting of the 2nd World Integrative Medicine Congress
Rong Xiang Xu
MEBO International Group, Beijing 100004, China |
[Abstract] A lecture named ¡®the human body life relies on the cells¡¯ was given by Prof. Xu Rongxiang in the 2nd World Integrative Medicine Congress Burn Satellite Meeting. This report mainly focused on three sections: the theory of skin regeneration on burns, the international progression of treatment for burns and the development plan of skin regenerative medicine.
In the first section, Prof. Xu, on the basis of clinical practice in burns, explained the basic theory and the application value of potential regenerative cells in detail, as well as the content of skin regenerative medicine on burns. Research tendency of the current international burn treatment discussed in the second section revealed that keeping moist physiological environment was the basis of medication for treating burn wounds. In the last section, Prof. Xu emphasized some details about the development of skin regenerative medicine, the professional committees, the center of science and technology, national medical network and the specific responsibilities of all the staffs.
[Key words] Regenerative medicine; Potential regenerative cells; Organ replication; Burn
Part One: The Foundation and Development of Regenerative Medicine
1 The trend of Life Science Technique in 21st Century
It has been 2500 years since we developed life science. We cannot obtain a holistic and accurate conclusion although lots of research work on human health and disease treatment has been done. What is the strongpoint of our current medical model? Can people live more than 100 years? What is the future of medicine? There is a hot argument on the above questions in the world science field. Why? The reason is that all medical theories are based on the nature including western medicine and traditional Chinese medicine, which both try to seek solution to health problems from the nature. After 2500 years¡¯ development, two factions in medicine emerged: western medicine and traditional Chinese medicine.
During the ancient Egypt war and development period of renaissance, the revolution of culture changed the view of people on human body and brought about human tissue biochemistry. Western surgery and antagonism medicine contributed lots to the human health and disease treatment. Traditional Chinese medicine also contributes to human health by its unique macroscopical remedy.
Scientists searched for furthest reducing the drug toxicity in human body and keeping human safe for centuries. Many supervisory organizations are established for medicine. So far, people do not revolute the medical system and still in drug system.
Over the centuries, the world scientists were making efforts on the research of decreasing maximally or preventing drug toxicity from entering the human body to maintain the body health, but till now, their thoughts are still confined in that without any revolution of the conventional medical system. Where should the human medicine go? By the end of 1980s, we started regenerative medicine research. The research base was established in 1987. In the past 14 years¡¯ tough and magnificent course, there were lots of academic controversies. We published results of burnt tissue healing without scars in 1989, atlas of skin regeneration by stem cells in situ in 2000 and discovery of PRCs in 2002. Heart, liver, kidney, pancreas, gastro-intestine, nerve and skin were successfully regenerated in situ and cultured in vitro. We established an integrated regenerative medical system and provided solid and reliable experimental and clinical basis for tissue organ physiological reparation and human longevity.
2 The scientific character and medical application value of potential regenerative cells
Molecular biology develops to cytology because of stem cells. In the clinical use of cytology, our burn regenerative therapy is a leading technique. Our stem cells are verified according to international standard. The PRCs in wound healing are examined according to the standard. The concept is made by us firstly. In the forties last century, doctor Worsen found the helical structure of DNA. Scientists spent the whole century to determine the base. By the end of last century, scientists definited the function sequence by the announcement of human genome. All scientists think hemopoietic stem cell is not embryonic stem cell. Because the hemopoietic stem cell has function during the process. But stem cell is a transitional cell. Stem cells are undifferentiated cells which can constantly proliferate and differentiate to tissue and organ cells. At last, the tissue organs are formed. The concept of our PRCs are different from that of stem cells because stem cells are dynamic and in embryo.
Ovum and sperm form a primitive cell of stem cell population with potential, named potential stem cells. They form embryo and gastrula. Finally they form organs and viscera. What is this kind of cell? It is potential stem cell which is primitive and undifferentiated. It has all potentialities of humans. After these cells continuously differentiate and form normal tissue organs, the differentiated cells are called pluripotent cells with part of the genetic information and continuous proliferating capability, such as hemopoietic stem cells which have the ability of haematogenesis and forming different cells, thus are the mode of embryonic stem cells. Everybody should not be confused that cells that cannot form normal tissues and organs could not be called stem cells. Since that kind of cells are the same with cancer cells. Somatic cells outside the body can only divide to third filial generation, at most forth, and have no ability of continuous division into organs finally.
In December of 2001, there were three sensational pieces of news about stem cells in the world. First, American president Bush announced that U.S. government determined to open the policy on embryonic stem cells research. Second, Chinese scientists accomplished the replication of gastro-intestinal mucosa in vitro. Third, the company ACT announced that the human cloned embryo in vitro lived for four and a half days. The news lasted for a month and had a great influence.
What is the embryonic stem cell? It is the cell which can proliferate continuously and finally develop into normal tissue organs. It is hardly to verify the stem cell, because the current level of biological technique can not realize the culture of living stem cells in vitro, and people have to study the stem cells in embryo developing process. However, the process of embryonic development can not be altered by humans. The process of zygote developing into human in body is called development. But it is a big controversy if this zygote could be confirmed as the stem cell. It is a developing cell since it develops and differentiates continuously, finally forming human tissue organs. If it cannot do so, it could not be called stem cell and normal developing cell.
People have lots of conceptions about regulating this kind of cells. Somebody said we used some factors of cells to regulate the change of cells into regulating stem cell. Some papers said to utilize enzymes to regulate et al. In two conferences held respectively in December 2001, and January 2002, people debated bitterly, especially all German scientists coincidently suggested systematic negative concept that held many factors had been studied, but none of them could be implemented to well regulate stem cells. What about our opinion? First of all, we completed cultivation cell proliferation in vitro without using any factor. We researched huge sums of factors without getting a real factor. Our concept is experiments proved no factor exists. What we used is life substance that is the reason why we could stand stable in science field. We know well about life substances.
The thought that we researched from results is unquestionable. The way of western study is exploration and never be sure where to go in the end. Our burns medicine consists of three steps. Now we have entered regenerative domain, from local wound surface regeneration to more refined studying, letting burn muscle and bone need no skingrafting, which is our endeavour target, step by step. On the first Academic Conference of Chinese Burns, Wounds and Surface Ulcers, we proposed to realize healing of deep second degree burns free of scars, gradually making the dream of three degree wound surface healing come true. Nowadays, we have achieved the healing without residual wound. If this wound appears, it means no skin regeneration occurs resulted from unqualified doctors. At present, we regulate the whole wound surface from the respect of regeneration medicine.
Our PRCs are cells existing in tissues, with cell morphous of a normal tissue. It has the potentiality of stem cell proliferation. A tissue cell directly forms a proliferate cell, finally becoming a new tissue organ, thus named PRCs. PRCs is generated from proliferate cell during its development. Stem cell proliferation is the expression of PRCs in the latter stage. PRCs initiation and activation is quite complicated. The process of a tissue cell evolving from static into motion involves lots of substances. The early stage of PRCs is static and they coexist with other tissue cells, and its discovering process is active, finally cloning and replicating into same cells, forming same tissue organs. The modes of cultivation are same both in vitro and vivo. Of course, what we finally realize is in situ, and in vitro is only a model.
Direction of our research is to follow life development, elaborate development process, tell PRCs discovery and origin, ovum and sperm revealing. The wound treatment has been deciphered as long ago as 1997.
The breakthrough of proliferation in situ of stem cells into tissue organs was published, revealing that it is achievable to take tissue cells and PRCs from any human tissue organ. As the whole law of 206 tissue organs was not completed in this proportion relation, some of them are found half to half, some one third, and these cells are the same with regenerative ability.
3 Medical technique composition of burns regenerative medicine
The engineering chart procedure of stem cells replication in situ has already been announced internationally, and published in Chinese and English version. This breakthrough is Chinese¡¯s invention. So far, it¡¯s difficult to depart from this chart procedure. The chart isn¡¯t drawn by me. We work hard for more than ten years to make it. One is cell in tissue, for instance potential stem cells, hereafter, although changes to regulate differentiation, but not using its factor. The human body surface has all kinds of feelings, the skin has feeling, it is an entirety, the small body is cell body, and also the cell membrane. Because the cell membrane is extremely thin till now, although there are so many theories, but the progress of cell membrane research is too slow, not quick like the gene technique research, but it is just cell membrane playing a very important part in life science research.
The epidermis and dermis have been mentioned just now, the binding of them can¡¯t be made beyond body surface. Only the life or organism fusion between cells can regenerate; this fusion is not blending together; it can decide own arrangement due to its attribute, no person can create, we must study the life continuation of human body. Hereafter, this kind of cell might differentiate into different regenerating tissue cell, which we call them different stem cells finally formed due to the proliferation ability.
Different stem cells link and form different tissues, the latter link to each other again, and it is what we have created. We must make good use of the word created by us, linking is the function of cell, not artificial. Cells link by Cell Bridge; some link directly by cell membranes, some has just no cell membrane, two cells without cell membranes directly link together and so on. By link it can form the tissue; again combines by each kind of tissue, the different tissue can install one component, a function unit, called tissue combination. Combine to a single unit.
The intestinal mucous membrane combines with four kinds of intestinal epithelial cells, four kinds of cells combines into intestinal mucous membrane, hereafter carries on the organ repair in situ, also may replicate into new organ, such as kidney pellet, renal tubule, such little organ can be replicated. This is the procedure chart, everybody must remember it, and that is our achievement and conclusion from practice of more than ten year¡¯s hard work.
In order to explain the procedure chart, we must review the course of burn treatment. We treat burn with skin regenerative technology in situ, if purely treat the wound or the knife wound without skin, it is very easy for doctor, but for burn treat, a complex wound mixed with good tissue and necrotic tissue, just the burn infection is difficult to solve. For one century the burn infection problem has not been solved, and then some people thought a method, completely cut away the skin, turns the burn into knife wound, so there is no burn. Therefore we said that there is no burn doctor except our regenerative medical technological expert in the world. What doctors are they? They are surgeons, they cut the burn, what they treat are not burn patients, change the burn patient into the wound patient, so that they treat are the wound and knife wound patient.
The traditional therapy is shaving eschar through surgery, not treating the burn, but cutting to expose the good tissue, and then transplanting the skin to cover the wound, we must make clear that it is the concept distinction between regenerative medicine technology and traditional burn technology. We are the doctors who treat the burn necrotic tissue and regenerate the living tissue of wound, because we regenerate a new skin organ again with survival burn tissue in situ, which foreigner could not understand, they saw the wound at that time, they were puzzled why the good tissue grew and the bad tissue liquefied, I said this is what we called Chinese regenerative medicine.
4 Combination of human tissue organ regeneration and replication technology in situ
1) Technology of stem cells activation and regulation in situ
Our Chinese philosophical thinking mode is maintaining the life, combining human with nature and strengthening the body resistance, this is the foundation of human body continuing instinct, certainly it is not casual; it is continued by life. What we first started and regulated is gene, starting gene is not regulating it, and it is the outside world informing them to start to replicate; we did not transfer the gene. Of course, we depend not only on it, but also mitochondria endoplasmic reticulum, they all have own gene system, certainly, there are still some other regulative methods.
2) Technology of stem cells cultivation in situ
Skin stem cells cultivation technology is to cultivate the skin cells. We have seen this kind of technology, and also have experimented, cultivation technology don¡¯t include the liquefaction of necrotic tissue. MEBT includes all the technology. The skin stem cells cultivation technology needs that the cultivation medium includes nutrient ingredient suiting for the stem cell¡¯s growth, now the medicine (MEBO) used in our clinical treatment, many ingredients waste, in the future it will be that special medicine is used in special stage. Now many effective components waste and were removed away along with liquefied necrotic tissue, the current cost for treatment is not very high, therefore we use the medicine together. So the stem cells cultivation technology will be an independent technology in the future.
3) Moist Exposed Burn Therapy of Non-traumatic liquefaction and discharge of burn necrotic skin
It is an extremely great technology, especially in the active international participation at home and abroad; their feeling shocked, the necrotic tissues don¡¯t become inflamed while liquefying? Many people thought liquefied means inflamed, this is the original concept. Our doctors are all clear, in ward inspection, when they saw the white matter appeared in burn patient's wound, they were happy, which means they didn¡¯t need the surgery, it was a speech in our China medicine: Without purulent secretion there will be no granulation.
Without purulent secretion there will be no granulation doesn¡¯t mean there are purulent secretion there will be granulation. It is because blood circulation of wound is rich, a lot of exudates exhausted; it shows that there exists blood circulation in wound surface. If the wound is red without any exudate, it is impossible to promote healing, because there is no life on the surface. Wound is open, open wounds need regeneration, and the regeneration of skin is backbone. So it is useless to make blood vessel in vitro. The blood vessel is the blood circulation, beated out by the heart pressure, because of the blood pressure in wound, the blood run forward, periphery blood vessel produces the blood vessel tree, we have a model of blood vessel tree, divided to four levels blood vessel web like pine tree, there are many collagens fiber cells or fibroblasts around blood vessel web. Then there are massive epithelial cell in it. Only in this kind of situation, can we realize the organ regeneration and replication in situ. Therefore the necrotic tissue¡¯s liquefaction exhausting is very important.
4) Exogenous wound tissue culture medium of tissue regeneration
Exogenous wound tissue culture medium of skin regeneration is culturing cells on the wound, and supplies blood ab intra, as there is not so much necessary thing in the blood, it needs supply exogenous, and it needs to study comprehensively about what to supply, we should supply what the cells eat and drink. This is modern medium called MEBO, and it will be more accurate and standard.
5) The technology of physiological control of bacteriotoxin
Non-sterilization controlling the bacteriotoxin infection of the wound and the physiology controlling bacterium function are all new terms. When we talk about infection, there is bacteriostasis or sterilization, but we can¡¯t follow that killing way, because any killing way is controlling and inhibiting regeneration, and is against life. We should conform to human life, which is to change the organ that bacteria endotoxin producing system using Moist Burn Therapy technique, and the protein produced by this organ is not so harm after changing it, and it becomes ball protein type. One biology expert of the scientists meeting says after the meeting, I will lead you to finish this experiment. I say it is very good. There are a lot of bacterias on the wound, without the bacteria, it will not work. And this turns back to the opinion about bacteria 200 years ago, among the period, there is antibiotic, and now we turn back, we have monograph to introduce the anti-infection treatment that will not kill the bacteria.
6) The technology of physiologically moist environment of tissue regeneration
Skin regenerates under the physiological moist environment, we must understand the concept, don¡¯t forget the physiological moist environment, once there is non-physical environment, the wound will develops abnormally, such as veining, infection. We need to maintain the osmotic pressure of the cell in the circumstance of normal osmotic pressure, and supply the nutritive material what the cell needs, we have a theory long before, which is called physiological moist, include the skin cosmetology, all the cosmetics are physiological, running sore and the cell dies. We must create a physiological moist environment in the environment that the skin develops, and the physiological index is very hard, because burning is as same as the organ copying, how can it regenerate without removing the necrotic cell? How can it regenerate without creating moist physiological environment? These are the topics what we will study.
7) The technology of endogenous support and micro isolation of the tissue regeneration
The technology of micro isolation of skin regeneration burn wound is that burn cream can form a nature fiber isolation coat on the wound. But how it works in the organ? All the same, it just needs us to create the moist environment well.
8) The technology of assembling of tissues into organs and the oxygen supply
The technology of supplying the oxygen and the nutrient materials to the tissue regeneration is the main factor of the tissue organ replicating process, the burn wound must be protected against the stimulating of the oxygen, if there is not charisma, and the air will be in, and the burn wound will be red, the exchanging excess between oxygen and the hemoglobin will induce damage, so we should cover the wound with MEBO, as it can prevent the oxygen. What kind of oxygen it uses? It uses that the cell brings with, don¡¯t think that it is mechanical oxygen, the hybaroxia oxygen is inorganic oxygen, is different from the oxygen in the body, without activity, experiment about cell proves that, once blowing to the cell , the cell will die soon after convulsion, it has bioactivity itself, don¡¯t see that one hemoglobin brings with one oxygen. That is not easy; there are many things to study.
Part Two: The Trend of International Burns Treatment
1 The situation of international burns treatment
Now there is only one faction in the field of burns treatment. We named it physically moist faction. U.S. FDA started to change the criterions of accepting drug products since last year. The function of the medicine firstly should keep the wound physically moist. And it is the standpoint of MEBO. FDA won¡¯t accept any case if it couldn¡¯t satisfy this criterion. America is a developed country and they accept new things fast, especially on the wound healing medicine. So far, the remedy goal on the Burns Wounds is to get rid of excising and skingrafting, and resort to regenerative therapy. It is the international Criterion. All of others are traditional methods.
What is the situation of burn treatment in China? 70% Clinic cases applies burn regenerative therapy, 30% cases still applies surgery. Besides, there are some folk prescriptions. Americans once used a biological dressing with epithelia. They are not Stem Cells. The company went bankrupt very soon, because doctors don¡¯t want to use it. They thought it was too complex and no difference from the scar healing. In the FDA of America, the registration of MEBO has been in phase two clinical trial. I believe that after being approved by FDA£¬the world belongs to us. Scientists in America are cooperative. We communicated very well.
Using the traditional drying technique to roast the wounds is a traditional method in burn treatment. The wound is much deeper even to the fat layer. This is surgical way. However, the burn regenerative therapy needn¡¯t cutting the necrotic tissues. It clears necrotic tissues by liquefaction and skin regeneration.
The liquefaction should be harmless. Pathological examination proved that the regenerative skin grew gradually. Skin regeneration is physical regeneration. This standardization treatment on burns wounds has been published in Blue Book for Burns Medical Technique.
In western world, doctors used some dressings to cover the cut skin. Only 40% cells on the dressing survived. We use the regenerative substances which produce the cell and help the skin regenerate.
In France, doctors put some cells on the on second-degree burn skin. Firstly, they cut the necrotic tissue until the bloody fresh tissue appeared. And then, they covered the wound with the dressing. The price is very high. Our ointment can make skin regenerate automatically.
The Second-Degree Burns should heal without scars. When they knew our technique, they admired the therapy.
2 Culture medium of potential regenerative cells
MEBO has its special framework structure. It bases on the structure of bee wax. We dissolve beeswax into very minuteness molecule estate and construct a framework from the molecule estate. The necrotic tissue can be changed to liquid form and then discharged from the wound. The frame form of MEBO is alterable depending on the change of wound temperature. There are two layers of MEBO after applying on the skin. The outer layer keeps its form and the wound touched layer is warmed up and transformed to liquid form. After applying, the liquid form MEBO reacts with necrotic tissues on burn wound, and the MEBO loses the lipophilic character and mixes with exudation and liquefactive stuff. Then the mixture moves to the outer layer of MEBO and be discharged out of skin. The new upper layer of MEBO continues to be warmed up and transformed to liquid form and then Hydrolysis, Enzymolysis, Rancidity, Saponification and Esterification happen sequentially, repeatedly and drainage automatically. This is the main mechanism of liquefaction of burn wound necrotic tissue. MEBO is warmed up and surrounds necrotic tissues: First, the grease base of solid form MEBO is warmed up by wound temperature and be transformed to liquid form, the oil is released and flows into the burn wound, divides the necrotic tissue into pieces and surrounds them, which will initiate the series chemical reactions between MEBO and necrotic tissues.
1) Hydrolysis: The first reaction is hydrolysis (One compound is decomposed under the effect of water). The residual water in necrotic tissues reacts with the necrotic skin under the effect and surrounding of MEBO, which will further initiate the series chemical reactions.
2) Enzymolysis: There are kinds of zymngens in remnant cells in burn wound necrotic tissues. Zymngens are the non-activate prosome of enzymes. After hydrolysis, the peptide of the zymngen in charge of the non-active function is removed. Then the big molecules such as protein, fat, carbohydrate are digested into small molecules by several kinds of enzymes. Thus, the necrotic tissue on burn wound is changed into molecular level.
3) Rancidity and saponification: Based on organic chemistry, acid and alkali chemical reactions are the reaction that obtain or lose electron (s). Rancidity reaction means that the amino acids, fatty acids are separated, the aldehyde keton¡¡oxide are formed from protein, fat tissues after the above-mentioned reactions. All these acidity compounds are composed by hydrogen ion and acid radical. These organic acids produce neutral salt and water after decomposion and combination. Saponification means the fat hydrolyzes in the alkalescence solution and produces glycerol and fatty acids.
Burns can make the wound tissue denaturalized and necrosis, produce lots of histamine, bradykinin, lactic acid, free radical and other acid substances, which are called ¡°Burn toxin". Under the therapeutical effect of MEBO, the burn toxins¡¡are decomposed, so that the direct damage of the wound are relieved; more addition, it reduces the damages of multi¡¡organs in the body by absorption of burn toxins. In one word, the result of rancidity and saponification is to decompose the necrotic tissue into neutral substances, which will protect the wound efficiently and alleviate the damage of burn toxins after absorption.
4) Lipofication and Esterification: The necrotic tissues are transformed into liquid form after above-mentioned reactions. The liquid necrotic tissues then react with surrounding MEBO and perform lipofication and esterification, which will¡¡ensure the necrotic tissue be liquefied and discharged from the wound eventually. MEBO has net-like frame form. It's composed by grease and surrounding beeswax. There are abundant linoleic acids (belongs to non-saturation acid), which can be decomposed with sterol stuff, aldehyde oxide, keton oxide, lipid, adipoidand, etc. This process is called ¡°lipofication". After that, the linoleic acids in¡¡MEBO bind with those substances and form esters, this is ¡°esterification".ª¥
In the process of liquefaction, esters can be degraded into acids; the opposite reaction is the acids are transformed into esters under the effect of esterases. The acid burn toxicity in necrotic tissue is reduced through these reactions, which also protect the moist physiological environment of burn wound and prevent¡¡its further damage. More addition, esters compound can protect surviving tissue of burn wound, promote wound healing and cultivate the neo¡¡regenerated skin tissue. Thus, it can be seen that Lipofication and Esterification are reversible biochemical reactions happening one after another. In this step, the decomposition between grease (linoleic acids) and liquefactant of necrotic tissue is not only the main base of burn wound moist physiological environment, but also the main elements which promote decomposition and liquefaction. After that, the necrotic tissue are transformed into liquid form of esters liquid mixture, the toxicity and irritation are much reduced and the mixture are easily to be discharged, which ensures the process of skin organ regeneration in situ.
MEBO has good compatibility with burn wound exudates and can form a fibrous isolation membrane in the course of wound necrotic tissue liquefaction. The membrane is composed of lipoids produced by the biochemical reactions of MEBO and lipoproteins complexes produced by exudates of plasma protein from wounds. The membrane tightly covers the wound surface, so that the neo regenerative stuff can attached to it and the wounds can be repaired in a regenerative way in moist physiological environment. ª¥
As a ¡°semi-permeable" membrane, the special composition of the fibrous isolation membrane enables its unique characteristics and function. It lies in between wound surface and MEBO. In both sides of the membrane, osmotic pressure is formed respectively. One side is hydrophilic (wound tissue) and the other side is lipophilic (MEBO). Exchanges of materials as ions are taking place, so that the metabolism products of the wounds can be excreted into the outer side of the membrane. Through the same mechanism, the nutritive and biologically active components of MEBO can go into the deep layer of the wounds and to give full play of its physiological and pharmacological effects to promote skin tissue regeneration and repair.
3 The function and development of potential regenerative cells
The potential regenerative cells (PRCs) exist not only on burns wounds, but also in all living tissues. Everyone knows that the fractured bone grows very quickly, why? Not all bones grow. Growth speed of cells in area containing maximum PRCs is most fast. Once bone cells get damaged, the damage is the first activation substance initiating PRCs.
In fact my research method of PRCs is to imitate the injured substances, the research of bionics. There is no factor generated after injury, but a kind of substance released. Certainly, inflammatory substances are also the source of activation, so the hydrogen ion, those stimulating substances. But that is just one aspect. This kind of activation cannot maintain and disappear after 24 or 48 hours of inflammatory reaction, then the cells stop growing and finally the tissues necrotize. If activation substances are provided continuously, cells could continue to grow. So I have to talk about the application value of science and medicine of PRCs today.
Before we research and explore PRCs, we must get to know the normal tissue cells, normal tissue cells. What we research about normal tissue cells is their morphous on skin. Everyone recognizes clear about the cell structure. Everyone saw the burns process, and published related articles as well. After discharging of necrosis tissues of skin, the wound surface is the mixture of epidermis and dermis histiocyte, which are proliferating. If we bind up the wound surface at this time, we can imagine that the wound will become pathological healing. So it needs to repair the defected tissues in loosen environment, which is the human potentiality, the instinct, decided by inheritance. Thus, defected dermis should be repaired by itself, and so does epidermis. The external protection layer mainly regenerates some degenerative cells that continue to regeneratie, forming dermis and epidermis. This is dynamic healing processes of wound surface. How do cells exactly regenerate in 20 days? On 20th day, we checked with stem-cell labeling method, discovering that there were no stem cells, and all cells became normal histiocytes.
The normal histiocytes include a basement membrane, epithelial cells containing cell nucleus.
The cell membrane is very thin, physiologically binding with basement membrane, forming a physiological structure. The binding without dermis and epidermis growing belongs to pathological combination, not physiological. The link of the epithelial cells is desmosome junction, but some cells¡¯ is direct membrane fusion, and some cell nucleuses belong to this kind of link. So all pathological healings aren't regenerative healing, and all physiological healings are regenerative healing.
Collagen fiber cells and fibroblasts are the cells that decide if scars could form. The growth of fiber cell is under better control in our laboratory. Of course, this kind of control was not realized by hormone, or other aspects, but completely by MEBO. We took out the fiber cells from skin and cultivate them. Fiber cells grew very quickly, and it was very easy to cultivate them. What is the function of MEBO? The result of experiment was: on the fifth day, cells grew very quickly; first, fiber cells were cultivated from fibroblasts, forming fiber cells; then observed the direct effect of MEBO on fiber cells; experiment was conducted with MEBO on the sixth day; the fiber cells did not like that kind, which is called inhibition or regulation?
In our concept of regenerative medicine, it is called regulation, the regulation between cells. We did not add any substance here, and there were no killing substances in MEBO, which only regulates cells to enhance the proliferative speed of epithelial cells. The relation of cells is mutual; one epithelial cell fitting four fiber cells is physiological state; one fiber cell fitting nine epithelial cells is pathological state, absolutely the scar state; one fitting nine should be scar hyperplasia. Fiber cells repressing by epithelial cells is the function, and the fiber cells control the growth of epithelial cell. So the substances in MEBO have the function of regulating cell growth, adjusting cells to physiological state. To realize physiological state, any artificial technique cannot make it. There is only one way for stem cell growing. As for how does stem cell grow and the stem cell growth sequence, they are still a secret, which we¡¯ll announce hereafter.
Some cells are being controlled. They change slowly and hereafter the fiber cells slowly disappear, certainly some stop life, this kind of life stopping is the inhibition of fiber cell itself. At the time of burn clinical treatment, it is a failure to get results with granulation tissue formation on burn wound. Remember, those, who did this kind of treatment, do failure jobs. After liquefying on burn wound, MEBO should be well applied timely. Then, the wound can be controlled in that position and grow upward. Stopping MEBO application or binding up the wound will lead quick fiber cell growth on wound surface due to losing control, forming scars after healing.
So we should not let granulation tissue grow. Once it has grown, how can we do? It is ok for you to wait, and let MEBO regulate it. If you don¡¯t wait, you can also slowly excise it with wound formation, then applying MEBO. Yet that isn't standard, since it is to build a new ecosystem at most. Once the epithelium tissue is overlaid by the granulation tissue, this kind of wound treatment is a failure. Although having waited for 200 days, cells succeeded in growing within several dozen days. Fiber cells could not grow due to great quantities of MEBO controlling. Function of MEBO is of regulating fiber cells. At present, all fiber cell regulation factors on sale internationally are not better than MEBO. MEBO regulates the physiological function of cells, no matter fibroblasts or epithelial cells. If all of cells are in normal physiological condition, they can't be disordered. All of them are one group. Once one side became disordered, all lost control. There are some fiber cells that grow very quickly, occupying the whole culture medium and bottles. They must be cancer cells, malignant cells. The same, the fibroblasts still have the characteristics of mother cells which are researched from the dynamic and molecular biology. The research of molecular biology is undertaken by Union Medical University, and has already been taken for two years. About this kind of topic, only after the research effect report come can the cell regulation be spoken clearly to everyone. The fiber cell is just the scar cell, so it isn't simple to be free of scar growing. We must well grasp our Clinical Studies. It is extremely important to keep wound surface without drying and stepping after necrosis tissue cleaning. Once wound surface become dry or steeping, the fiber cells grow without delay. Scar growth can be naturally inhibited only when physiological moist is kept on wound surface and cells are maintained in normal physiological state.
Then turn back to explain a concept, it is PRCs. It is in the normal tissues, also including fiber cells. Please don¡¯t think there are no potential regenerate cells in fat connective tissues. There are potential regenerate cells in the bone, subcutaneous tissue, and muscles. Now the expression of every type of PRCs is different from each other, so we should explain them one by one.
To study the riddle of explaining the life, we must remember the instinct of the PRCs. This potential instinct is not created, but discovered by us. In fact, everyday we live in the battle relationship between cell living and the death. Why did we say that it is chromosome telomeres that record the age, and with the age increasing, the telomere in the chromosome is smaller and smaller, who detected this? This telomere doesn¡¯t display any certain cell. All the body cells are in one pace, proving that all of them are changing. If the body cells don¡¯t change, then the telomeres don¡¯t change. Only the telomeres change, every cell shows that they are all changing, that is proliferative cell or a PRC. It is impossible for the tissue cell not to change. When you are 20 years old, you can¡¯t find cells owned by 10-year-old you. So there is not any scientific evidence for the rejuvenation idea.
What we study about the potential cell is its potential. The cell of a 70 years old man is 70-year-old cell, can¡¯t be other age. Burns are known to everyone that the skin on wound surface of a 50 years old man still is 50-year-old skin after healing, and it cannot be 2-year-old skin. The innate thing can¡¯t go back, only go ahead.
The concept of PRCs in tissues is that they have the potentiality of proliferation and regeneration of the stem cells; they reside in tissues with the form of common cells. We should remember them; it is a macroscopic concept and will be subdivided in more detail. What way do these cells express in? What process do they evolve in? What stage do they enter? We will fill up this concept in the future. Let us review it once more. Stem cell proliferation is one cell divide into two, two to four, and some of them are symmetrical to each other, while other not. Though this kind of expression and expression in vitro has not been published, they are coherent. So, one special gene expression is expressing in the process of the change and maturation of the stem cells.
A tissue cell is dynamic which keeps on proliferating. After two or three generation, it will copy the cell according to the need of composing a new organ. Cells will join to be tissue, and tissues will recombinant an organ. About the cell junction, it is not the proliferation of the stem cell. The tissue cell forms mucous membrane which is tissue organ.
Please keep this process in your mind. In order to settle base for the copy of the situ organ, this process begin with the skin. We have recorded and edited it in the book. The process is the foundation of our regenerative medicine, is also the basic atlas. Human now only guess their lives and they haven¡¯t drawn the regeneration atlas. We need to establish some new concepts, such as organ. It is tissue unit with living function. This concept is in Human ergology translated by Academician Wu Dechang and the Human Anatomy by Zhang Zhaoyou. We have used it to define the concept of organ. To show our result of in vitro cell experiment with tissue cell, the new organ established by the cell called tissue organ. The establishment and division of 206 tissue organs is a scientific way. In fact it is very simple. It is the function unit of life, and this function unit has relation with others. It exists with molecular shape. The function unit is divided into 206 tissue organs. With the growth of the life science, there will be much more tissue organs.
The division of the concept is the base of our regenerative medicine. It is our theoretical foundation. Life substance has special definition. It is not the base of life or the structure thing of life. It is a substance activating and maintaining the proliferation of the cell and tissue organs. The active components in the Chinese medicine and the western medicine can stimulate the cell and make it dead. Life substance firstly should maintain the life rule, then on the base of maintaining life rule. It has active function and proliferate function. These functions include active, irritate and supply medical substances to life. Tissue organ is our unified concept, we offer that potential cell firstly forms tissue, and then forms units with function. It is called tissue organ. This concept is established by us. Human life unit is different from human body of anatomy. Cell is the smallest human life unit. The biggest one is human body.
Human life is an action process. In human life, there are 206 tissue organs in the body, which are composed by life units. These units joint together with their life function and handle everyday under the control of the brain. So this forms human life. Without brain, it is not human body, which is a gork.
Human life action can be divided into the brain, the five sense organs, heart, liver and so on. According to the function of human life action, and human frame structure is composed by the blood circulation system, nervous system, locomotor system and support system. These frame structures have life function.
According to regenerative medicine, tissue cells are cultured in vitro, then regenerate the potential regenerative cell clones and form the primary tissue. Then the primary tissue forms the tissue organs. We look for and verify the substances that maintain and regenerate tissue organs. We apply the substances to the dysfunctional tissue organs. New tissue organs are regenerated in situ by the proliferation of potential regenerative cells. These new tissue organs replace the dysfunctional tissue organs. This technique belongs to us.
Besides the clinical doctors, there are many scientists to research the regenerative medicine in our team. Scientists provide mature techniques to clinical doctors. So we have exclusive experience of this. The 21st century belongs to Chinese and the future of life science belongs to us.
Part Three: The Academic Development Planning for Regenerative Medicine
1 The international therapy specification and standard for burns wounds treatment
The Chinese Burn Association of the Integration of Traditional and Western Medicine (CBAITW) formally remind you here that from now on all standards for clinical application of Regenerative Medicine (RM) should be in accordance with the Blue book for Burns Wounds Technique. This is because our nation has publicized the new legislation on the behavior of medical experts in the aim of standardized dealing with medical accidents. The standard put forward by the Blue book for Burns Wounds Technique shall be used to judge whether your way of burn wound treatment is right or wrong.
The experts should evaluate the burn treatment technique, if the surgical way of treatment being adopted, the law suits occur later would hold full responsibility of those experts who made the decision. Therefore, whether you are the evaluator or emergency consultant expert, you are supposed to express your opinion as Blue book for Burns Wounds Technique (Hereafter referred as Blue Book) stipulated. The Blue Book has now been adopted as international standard and will be published in English in USA. If we have new standards to be added, the second volume of Blue book will be published. There are many new terms raised by all of us during each session of conference, which will be settled down finally. The CBAITW is a national level academic organization acknowledged by government, it has its rights, obligations and responsibilities.
The Blue Book has described the standard of MEBT/MEBO in detail and has been reported to the competent department as a formal standard. Together with video data, we should always remember all standards and specifications. The Blue book had been acknowledged by our government, it¡¯s a legal medical technique in our nation.
2 The command of burn emergency aid
Our expert consultant team has the right and obligation for the command of burn emergency aid. We have set up a special MEBT/MEBO committee of which experts have rich experience in curing severe burnt patients are selected. Consequently, burn emergency aid may contact this committee directly whenever in need. The consultant experts should formulate a unified specification to cure the patients.
3 Obligations of the expert team
The obligation of the expert consultant team is the same as CBAITW, every member of the team should strictly follow the standardized specifications. The experts have the medical right and your opinion should be seriously considered by hospitals.
4 Qualification of the expert team membership
We are planning to increase the number of expert team member. They will be chosen according to their extensive burn treatment level and the thesis published. The purpose of setting up the committee is to standardize the application of MEBT/MEBO. Not only should our technique be developed in burn wounds treatment, but also the ulcer and traumatic wounds treatment.
5 Obligations of magazine editing members
The editors of the magazine should publish at least two high quality theses each year. Talented persons should be discovered, trained and absorbed into the member of the magazine editors.
We should learn to accumulate and sum up the clinical experiences in order to be used as academic data. Clinical data should be collected from individual case to integrate to the whole.
6 Increase the number of the scientific and technological prize for wounds and ulcers
Ulcer and traumatic wounds treatment is a larger issue than burn wounds treatment. It¡¯s the largest issue in the US, the concerned doctors in US are supposed by legislation to use the burn, ulcer and traumatic medicine. The FDA is only to accept medicine with moist character. There is no dry therapy in America, burn wounds therapy is attributed by both foreign and Chinese specialists. It¡¯s a development period of regenerative medicine. We should not confine ourselves to burn wounds treatment, however, to enlarge the application of the regenerative medicine to 206 human organs.
We shall continuously explore and research in science field, adopting the idea complied with life, ensuring potential regenerative cells to repair and replicate injured organs, in the aim of realizing life relay through self physiological reparation of tissue organs.
Let¡¯s work together to make the dream of human longevity come true!
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