• Regeneration of Skin with Normal Physiological Structure and Function

Figure 1 shows a typical process of wound healing and skin regeneration of patients treated with MEBO’s regenerative system. Compared to conventional burn therapy which would require skin grafting for extensive, deep burns, and often cannot avoid disfiguring scarring and disablement, Dr. Xu’s approach potentiates and maximizes the ability of the body to heal itself by using MEBO’s regenerative system (which includes applications of the wound ointment and unique techniques of wound management) to maintain the burns wound in an optimum, physiologically moist environment and to supply vital nutrients to enhance the regenerative ability of the residual viable tissue.  Based on extensive preclinical and clinical research that produced evidence showing the dynamic changes of cells at both the cellular and tissue levels for adult humans undergoing wound healing under the influence of MEBO wound ointment, Dr. Xu and his research team have shown that the regeneration of skin under the conditions provided by using MEBO’s regenerative system recapitulates embryonic development and mimics scar-less wound healing of a fetus. 

Dr. Xu and his research team demonstrated for the first time that embryonic epidermal stem cells are induced or activated and able to proliferate in adult humans under conditions favorable for physiological tissue repair and organ regeneration. Such regenerative conditions are provided by applying MEBO wound ointment topically to the wounds and using unique techniques of wound management.

• Embryonic Epidermal Stem Cells Detected in Wounds Treated by Using MEBO’s Regenerative System

During the treatment of the patients with at least deep partial thickness burns (that would normally require skin grafting if treated with conventional burn therapy), vigorous cellular activity on the wounds was observed in the presence of MEBO wound ointment.  These “hyper-active” cells are confirmed to be cells expressing keratin-19 (K-19) detected by immunofluorescent staining with a monoclonal antibody against human K-19. Figure 2 showing dynamic changes in the level of K-19 expressing regenerative cells monitored at different time points during wound healing of a patient under the treatment of MEBO/MEBT.

Consistent with the regeneration of functional skin organ of an adult, application of MEBO/MEBT to human adult limb regeneration has produced groundbreaking clinical results.  The clinical evidence collected from near a thousand cases shows that after treated with MEBO wound ointment adult patients with damaged or lost limbs can recover with fingertips regenerated with normal physiological structure and function. 

• MEBO Proves that Regenerative Potential of Adult Humans is Much Stronger than Previously Expected 

It has been well established that vertebrates of lower species, particularly urodele amphibians (common called “salamanders”), have an intrinsic capacity to regenerate a variety of body parts, including limbs, tail, jaw, and retina.  In higher mammals, examples of complex tissue regeneration are less common but can be seen in the seasonal regrowth of deer antlers.  For humans, there is description of distal fingertip regeneration in children, but not in fully developed adults.  Some concluded that regenerative potential declines with the evolution of complexity.  As here, application of MEBO/MEBT to lost or severely damaged fingers of adult humans could not only repair the wounds but also regeneration of fingers with normal structure and function, including bones, muscles, nerves, blood vessels, connective tissue, finger nails and skin.  These results demonstrate that the regenerative potential of adult humans is much stronger than previously expected.  Consistent with what was observed for the regeneration of skin of burn patients, establishing an appropriate environment favoring regeneration and providing materials to the wound to stimulate and sustain the regeneration is the key to the success.

III. Certain Somatic Cells in Every Tissue or Organ of the Body are Potential Regenerative Cells

At the cellular level, it was found that ordinary adult somatic cells isolated from animals could be induced to behave like stem cells under the conditions provided by the MEBO regenerative substances in cell culture.  More surprisingly, the cells proliferated and differentiated orderly to form tissue with substantially the same physiological structure and function as the corresponding tissue in vivo and in situ.  To differentiate such cells from normal adult stem cells such as basal epidermal stem cells, Dr. Xu coined these cells “potential regenerative cells” (PRCs).  

• Comparing PRCs with induced Pluripotent Stem Cells (iPS Cells)

Based on further cellular, animal experiments and clinical studies, Dr. Xu proposed that PRCs exist in virtually every tissue and organ of the body and may not need specific “niches” to be tucked away.  Unlike the iPS cells produced by inserting exogenerous genes in order to maintain an undifferentiated state (see review by Yu & Thomson (2008) Genes & Development 22:1987-1997), the native PRCs existing in the body need not to be genetically engineered in order to be activated or induced to behave like stem cells.  Unlike the iPS cells, the PRCs in the presence of the MEBO regenerative substances do not differentiate chaotically to form tumor-like cell masses.  Instead, the differentiation of PRCs follows a lineage specific to the site of the body from which the PRCs are originally isolated.  Such a path is clearly illustrated by the formation of the intestinal villi from small intestinal cells isolated from normal human intestines. In the presence of the MEBO regenerative substances, single, isolated adult intestinal cells proliferated and directionally differentiated to epithelial cells, goblet cells, Paneth cells, and endocrinal cells, which adhered to each other to form the distinct brush-like structure of intestinal villi in the cell culture.  Similar formation of physiological tissues from PRCs from various tissues and organs, such as heart, lung, liver, pancreas, bone marrow, and nerves, has been observed in the cell culture in the presence of MEBO.

More significantly, a series of products based on MEBO regenerative substances have been and are being developed to promote tissue and organ regeneration in the body.  For example, an oral formulation based on the MEBO regenerative substances has been clinically tested and found to be able to repair and regenerate the mucosal lining of the gastrointestinal tract without scar formation, which is consistent with the regeneration of skin using MEBO/MEBT.

IV. MEBO regenerative substances selectively inhibit cancer cell growth while promote regeneration of normal tissue

Having proven that the MEBO regenerative substances are able to stimulate and sustain vigorous growth and directional differentiation of healthy human cells, Dr. Xu asked the converse question: “How do MEBO regenerative substances affect cancer cells?’  A series of cellular and animal experiments have been designed to test the effects of MEBO on cancer cells in vitro and in vivo.  It has been demonstrated that not only cancer cells, but also immortalized cells transformed using virus, are not able to sustain their growth in the presence of the MEBO regenerative substances; instead, they undergo a growth arrest which is followed by cell death eventually.  Controlled cellular studies showed that healthy human cells thrive, while cancer cells from the same organ stop growing, in the presence of the same reagent containing the MEBO regenerative substances.  Consistent with the results obtained from the cell culture experiments, the cells in human tumor tissues cultured in vitro also stop growing, leading to a disintegration of the tumor tissues.  Such unique dual functions of MEBO open the door to future cancer prevention and treatment that could circumvent common problems associated with conventional cancer therapy, such as adverse cytotoxicity for healthy cells in the body and compromised immune system.

Currently, clinical studies of terminal cancer patients are undergoing in China to test the ability of the MEBO regenerative substances to combat cancer and re-establish the homeostasis of the body by stimulating the growth of residual healthy progenitor or stem cells to regenerate tissues/organs, and by halting the growth of transformed or malignant cancer cells so as to eradicate cancer cells and tumors eventually.  Preliminary encouraging results were obtained from the first phase of this study of terminal cancer patients who have failed medical cancer treatment, and whose cancer includes the most common and lethal ones: lung cancer, liver cancer, gastrointestinal cancer, breast cancer, prostate cancer, ovarian cancer, brain tumors, and leukemia.  Among the 204 patients who have participated in the treatment with MEBO’s innovative total nutritional therapy (that utilizes the MEBO regenerative substances) for more than 4 months, those who started at a relatively stabilized stage have a survival rate of 100% (16/16); those at a stage of disease progression have a survival rate of 61.54 % (77/125) and are currently stabilized; and those at a stage of end-of-life salvage have a survival rate of 33.33% (20/63).  These data are distinctively different from the half-month survival rates of end-of-life or terminal cancer patients under the international cancer treatment standards.  In this study there is a significant increase not only in the overall survival rate, but also in the survival rate separately for various stages and types of cancer.  These preliminary results from the clinical study bring hope to us in our fight against cancer.

V. Summary

By harnessing the natural power of our body to regenerate or heal itself, MEBO is also developing additional MEBO regenerative medicines and nutrients that will significantly impact human health, including remedies for preventing or treating neurodegenerative diseases, diabetes, and other diseases associated with organ degeneration and failure.  If successful, we believe that these new technologies and approaches may allow us to expand our life expectancy and live a more healthy and productive life. 

The core technology of MEBO lies in in situ regeneration of tissues and organs of the human body by providing regenerative nutrients and establishing favorable regenerative environment in the body.  Under the regenerative conditions provided by MEBO, the injured, diseased, transformed or aged cells in the tissue and organ can be replaced in situ with normal, healthy cells, thereby restoring physiological structure and function to the body. 

• Background

For the longest time people have been exploring the frontiers of science and technology to look for materials and means to maintain health, to prevent and treat diseases and to live a long, productive life.  Modern medicine has contributed significantly in the shortening the distance for reaching theses goals.  However, merely treating the diseases by suppressing the symptoms or by inhibiting the infection of exogenous pathogens is often insufficient to completely restore physiological structure and function to the body as the tissue and organ has already been damaged. Fundamentally, the key to reaching this goal—restoration of physiological structure and function—lies in the regeneration of damaged tissues and organs in the face of injury, diseases, and aging.  

What is regeneration actually?  Regeneration maintains or restores the original, physiological structure and function of the tissues and organs in the body.  Stocum (2006) Regenerative Biology & Medicine page 1, Academic Press.  Regeneration can be manifested in the restoration back to the state of tissue or organ prior to the injury, disease, or aging, or, more significantly, in the generation of tissue or organ in a more youthful state as compared with that right before the injury, resulting in restoration(as shown in the clinical data obtained by MEBO. See Sections below). 

Across the phylogeny of the multicellular organisms, from the primitive the common ancestor of modern multicellular organisms—the sponge—, to planarians, and to lower vertebrate amphibians such as salamanders, it has been found the remarkable ability to regenerate in the face of massive loss of tissues.  As shown in Figure 1.0.1, salamanders are the only vertebrates able to regrow lost limbs, as well as many other body parts, throughout their lifetimes—and they can do it repeatedly. Muneoka et al. (2008) “Regrowing limbs: Can people regenerate body parts?”  Scientific American Mar. 17. Studies of how a limb forms on the salamander have revealed that the process begins with rapid wound closure and a rush of cells from stump tissues to the amputation site. The next stages involve reversion of those cells to an embryonic state and their building of a new limb following the same steps as in embryonic development.  In the higher vertebrates, such as mice and humans, such an ability to regenerate (although preserved during prenatal development) has been widely regarded as being lost during adult life.  Instead, in response to the injury an adult human body may be able to repair the wound by covering it with scar following a process of fibrosis, resulting in disfigurement and disablement due to the loss of tissue structure and function. Gurtner et al. (2008) “Wound repair and regeneration” Nature 453:314-321. Gurtner et al. (2007) “Progress and potential for regenerative medicine” Annu. Rev. Med. 58:299-312. Colwell et al. (2003) “Fetal wound healing” Front. Biosci. 8: s1240-s1248.

In particular, hypertrophic scar formation following burns and trauma remains a terrible clinical problem. Sheridan & Tompkin (2004) “What’s new in burns and metabolism” J. Am. Coll. Surg. 198:243-263. As shown in the Figure 1.0.2A, hypertrophic scars begin as small cutaneous fibrotic regions (arrowheads), which develop into gross scars (arrows) over time. Following burn injury, a patient shows severe joint contracture (Figure 1.0.2B). Radiograph of the same patient shows erosion of the bone secondary to disuse and contracture (Figure 1.0.2C). After years of treatment and physical therapy, this patient will only regain minimal hand function. Aarabi et al. (2007) “Hypertrophic scar formation following burns and trauma: new approaches to treatment.” PloS Medicine 4:1464-1470.

To many, it remains an elusive dream that the complete restoration of physiological structure and function could be achieved in an adult human body in the face of massive tissue loss. 

Currently the field of life sciences is actively engaged in the basic research to study why the human body cannot regenerate like lower vertebrates and how to suppress fibrotic wound repair and to promote regeneration.  Ranging from ex vivo cultivation of human stem cells, to cell therapy, gene therapy, and the application of recombinant human growth factors, so far consistent success in the clinic has yet to come or remains limited in certain areas.  Stocum (2006) Regenerative Biology & Medicine, Academic Press.

• MEBO’s Innovative Approach to Creating Regeneration of Human Body

Through a quarter century of research and clinical practice, Dr. Rongxiang Xu has led a team of scientists and clinicians to create regeneration of human tissue and organ in situ, i.e., at the site of tissue or organ in the body that has been injured, diseased, malignantly transformed or aged. Starting with regeneration of the skin lost due to extensive, deep burns, Dr. Xu has established an integrated system to enable the body to utilize its intrinsic potential to regenerate and repair itself and successfully restore the structural and functional integrity to millions of wound patients.  

Using the skin regeneration after injury as a model for human body regeneration and based on clinical observations of the patients and examination of a large number of tissue samples obtained from the patients, Dr. Xu distilled from the clinical practice and research and developed a novel theoretical foundation for human body regeneration, which is further applied to the regeneration of internal tissues and organs of the body. 

According to Dr. Xu, fundamentally regeneration in an adult human requires the following three basic components:

1) Potentially Regenerative Cells (PRCs) that reside in every tissue/organ of the human body: In contrast to the popular belief in the field that there must be special niches reserved for the so-called stem cells or progenitor cells that can be utilized for regeneration in response to injury or disease, first in the regeneration of the skin of severely burnt patients under the conditions provided by MEBO and later clinical practice in regeneration of other tissues and organs, Dr. Xu discovered that normal somatic cells in the body, regardless of their locations, possess the ability to be converted into PRCs that later participate in the regeneration process by functioning like stem cells to produce multiple cell types needed for forming the new tissues in situ in order to eventually achieve regeneration of the body.

2) Exogeneous Regenerative Substances that serve as a nutritional source to promote and sustain orderly proliferation and differentiation of the PRCs to restore structure and function.  It is well established that unlike the prenatal development, spontaneous wound repair in an adult human body would go down the pathway of fibrosis to form scar tissue.  As shown in the sections below, successful clinical application of the MEBO technologies and products reveal that to steer the body to go down the pathway of regeneration, exogenous regenerative substances must be provided as the building blocks for such a reconstruction process.  Based on clinical observation and in vitro cellular studies, Dr. Xu also proposed the regeneration of an injured or otherwise defective human organ starts from the regeneration of a smaller, basic functional subunit, termed a “Tissue-Organ,” which is composed of multiple cell types that can be provided by proliferation and differentiation of the PRCs residing at the site of the injury or defect. 

3) Enabling Regenerative Techniques that create a physiologically favorable, regenerative environment to assist and sustain the body’s regeneration.  It is insufficient just to have the cellular and material foundation for the regeneration process to go smoothly, local and systemic environment also plays critical roles.  Still based on clinical applications of the MEBO technologies and products, it has been found that specific clinical techniques are required to create a regenerative environment so as to steer the body away from the default pathway of fibrotic repair to that of physiological restoration of correct tissue structure and function by following the correct lineage of stem cell proliferation and differentiation in situ.

As shown in the representative examples below, clinical application of the MEBO technologies and products has yielded spectacular successes in treating millions of patients in broad areas involving injured, diseased, or aged skin and internal organs.  The emerging of this revolutionary system heralds a new era of human life sciences and will have a significant impact on medicine, healthcare and human life in general.