• 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.

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 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, 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.
4. As shown in the representative examples below, clinical application of the MEBO technologies 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.