Cell Immun was founded with the aim of ensuring professional services and extensive care for physicians as well as patients. Due to long-term experience and reliability we are able to meet the needs of our clients.
Our team cooperates closely with carefully selected physicians in Germany and all over the world. We guarantee highest quality and effectiveness. Our ultrafiltrates are produced in close cooperation by a well-established laboratory with long-term experience and know-how.
Our activities are based on the historical research by Prof. Dr. Paul Niehans, conducted in the beginning of the last century, followed up and compiled by Prof. Dr. Albert Landsberger, University of Heidelberg.
Molecular Cell and Immunotherapy
Basis for the development of novel biologics to promote health
Molecular cell and immunotherapy (MCIT) is a promising health-promoting therapeutic approach for the treatment of subacute and chronic diseases, including cancer. It is based on health research for the clinical application of preparations from stem cell tissues and aims to strengthen the body's own immune defence and cellular regeneration. With the help of new molecular biological methods and artificial intelligence algorithms, we are nowadays able not only to isolate and analyse individual signal molecules from stem cell tissue preparations but also to assign molecule clusters to their biological functions. Using this knowledge we are increasingly able to develop novel biologics with health-promoting properties.
S. Dreyer, Humanio - Institute for Cellular Therapy, Mariahilfstraße 14, 55411 Bingen, Germany
O. Kuhnke Ortho-Bio-Med, Centre of excellence in biological, complementary and regulative medicine, Via Industrie 14, 6535 Roveredo GR, Switzerland
This review summarizes the development of the MCIT from earlier xenotransplantation to the isolation of stem cell tissue-associated molecule clusters with biological functions to the clinic-compliant biotechnological production of novel biologics.
The medical root of molecular cell and immune-therapy dates back several centuries. From the very beginning, this kind of therapy focuses on the use of defined components of organ tissues to regenerate organ systems or to activate the immune system against pathogens and cancer.
Therapeutic approaches pointing in this direction are already evident in the writings of Aristoteles (384 - 322 BC) and Hippocrates of Kos (~370 BC). However, it took until the half of the 19th century until the German physiologist Arnold Adolph Berthold first described the regenerative effect of testicular implantations in castrated chickens in 1848 . Together with the English neurologist Charles Eduard Brown-Séquard (1817 - 1896), who demonstrated the effect of xenogenic tissue extracts on the human organism, he paved the way for both the modern endocrinology and the treatment with cell tissues or the transplantation of entire organs .
In a pioneering work the Swiss Nobel Prize winner Theodor Kocher (1841 - 1917) transplanted fresh allogeneic thyroid tissue in the neck region under the skin of a young man to reduce side effects after thyroid surgery . However, these first transplant attempts with adult allogeneic or xenophobic tissue were largely frustrating without more detailed knowledge of immuno-logical rejection reactions. In this context, it was particularly interesting to note that longer-term therapeutic effects beyond short-term hormone effects could only be achieved if using juvenile xenogeneic organ tissues - at that time primarily from lamb. In fact, recent studies show that embryonal and foetal mammalian tissues are more immune-tolerant than adult tissues, primarily due to the different ways antigens are presented .
The therapeutic principle was relatively simple. Diseases were assigned to certain degenerative or functional changes to specific organs. On this basis, patients were treated with the same organ from healthy foetal animals – in most cases from lamb. The parenteral therapeutic approach focused on the repair of damaged glandular tissues or organs such as heart, kidney, liver or lungs, but also on the treatment of age-related diseases, neurological diseases, developmental disorders, cancer, etc. Niehans became famous in 1954 when Pope Pius XII, who was seriously ill, recovered after being treated with Niehans' cellular therapy. As a result of this therapeutic success, kings, presidents, world stars and magnates pilgrimage to the "Fountain of Youth of Bern" to be revitalized by Niehans [5,6].
In order to be able to produce the organ tissues on a pharmaceutical scale, Niehans developed the lyophilisation technique of organ tissues in cooperation with the companies Rheinchemie and Nestlé at the beginning of the 1950s . In this process, the foetal organ tissues were gently freeze-dried into dry powder. This form of lyophilisation not only largely preserved the molecular structure, but also allowed to storage for a long time under suitable storage conditions. For the first time comprehensive testing and characterization of product batches became possible . In addition, many times more economical pharmaceutical manufacturing method enabled significantly larger production capacities and lowered product prices. The transition of an "expensive elite medicine" into a "health medicine for everyone" had begun. Noteworthy in this context was also the observation of many practicing physicians that lyophilised organ products sometimes had even a better clinical effect than the original fresh cell preparations [9,10].
As the popularity of cellular therapy increased, so did the criticism from academic medicine. While in the pre-antibiotic era the justified fear of bacterial zoonoses and the very short shelf life of the fresh tissue suspensions were criticized, the medical discussion between supporters and opponents of the therapy with xenogeneic organ cell tissues became much sharper in the 1980s . The supporters of cellular therapy were able to come up with numerous clinical case reports and a few smaller clinical studies. Unfortunately, the medical data were mostly not taken seriously by the opponents and were declassified as pure empirical medicine [9,12]. In addition, there were fundamental concerns about the allergenic potential and the fear of zoonoses, especially bovine spongiform encephalopathy (BSE).
From the very beginning, however, the greatest weakness of cellular therapy has been the lack of scientifically reproducible mechanisms of action. As a consequence, no scientifically confirmed clear medical indication could be assigned to the organ preparations, which makes it difficult to weigh up the risk-benefit ratio of this therapeutic approach until today .
Until a few years ago, also controversial discussed was the therapy with connective tissue or its components, especially with polysulfated glycosaminoglycans (GAG). A leading figure in this field was Albert Landsberger (1937 - 2016), a renowned professor of anatomy at the University of Heidelberg. Among other things, he conducted research on the regenerative and regulatory properties of connective tissue and on the function of tissue-resident immune cells, especially mast cells. Already in his early work, he pointed out that the connective tissue of organs, especially the umbilical cord tissue, is rich in GAG. These polysulfated polysaccharides have anti-inflammatory and anticoagulant properties as well as lasting effects on the intercellular transport of substances. In particular, he focused on the function of degranulated tissue-resident mast cells in cancer tissues. He found evidence that degranulating mast cells released large amounts of GAG and that these GAG are involved in the inhibition of cancer growth [13,14]. Landsberger also demonstrated that GAG selectively increase intracellular uptake of drugs, e.g., cytostatics, thus enabling tumor-specific "drug targeting" . Based on these findings, he developed ResistocellTM, a mixture of (i) GAG, (ii) Dextran 60 - to activate mast cell degranulation -and (iii) lyophilised xenogeneic umbilical cord tissue for deep subcutaneous administration and supportive therapy of cancer patients .
Numerous case reports and clinical studies have shown that ResistocellTM improved the efficacy of various cytostatic drugs and at the same time reduced their side effects [15-18]. Even an exclusive treatment with ResistocellTM could, as shown in few cases, induce cancer regression. Moreover, the preparation supported bone marrow regeneration and the regulation of the gastrointestinal tract. In addition, ResistocellTM reduced infections and showed a favorable influence on inflammatory processes and/or autoimmune diseases. Medical case reports on the synergistic effects of ResistocellTM combined with cellular therapy attracted considerable attention. In this context, the immune regulatory effects of ResistocellTM seemed to have a benefical impact on the efficacy of cellular therapy not only in adults but also in children with inflammatory diseases, wound healing disorders and genetic deviations [9,12].
Our preclinical research and analysis of clinical cases on (1) cellular therapy according to Niehans and (2) on therapy with (umbilical cord) connec-tive tissue according to Landsberger have largely confirmed earlier findings. Based on both cell experiments and animal models, our study identifies the potential of juvenile organ and umbilical cord tissue on regeneration and immune biology across different species. However, the complex composition of the umbili-cal cord and organ tissue lyophilisates was prob-lematic from the beginning for the exact classification of the mechanisms of action. These are not only composed of signaling and structural mole-cules and the cellular compartments of various cell types, they also contain all components of the extracellular matrix, such as hyaluronic acids, polysulfated GAG, collagens, phospholipids, glycolproteins, electrolytes, minerals, etc.
In order to study and define individual molecules or molecule clusters, we fractionated the tissue preparations and analysed the contents bio-chemically and molecularly. On this basis, we tested defined molecules and molecule clusters in the cell model for their biological activity. In addition to a large number of (stem)cell and cancer cell lines of different species, immune cells and organ-specific tissue cultures (3D matrix) were also used. Among other things, the influence of the purified organ tissue fractions or molecules or molecule clusters on cell vitality, cell migration and cell differentiation as well as on the activity of immune cells of the innate or acquired immune system was investigated.
In the course of our research, we found evidence of a(n)
- tissue-specific regeneration
- redifferentiation of cancer cells
- reprogramming of adult stem cells
- non-specific activation or inhibition of specific immune cells
- antigen-specific modulation of immunologic regulatory and effector cells
The breadth of the observed biological effects surprised us, but fit well with the previous research and clinical studies already cited in the introduction. They are well comprehensible from a developmental-biological point of view, since the molecules or molecule clusters we isolated and tested were primarily stem cell factors or stem cell antigens, which also play a central role in embryonic and foetal development.
Today, we are not only able to assign the biological activity spectra to individual tissue fractions or molecule clusters, but also to optimize their bioavailability and efficacy in cell and animal models. For this purpose, we developed novel GMP-compliant manufacturing processes. These allow a significantly more efficient transmucosal bioavailability of the fractionated organ tissue suspensions while maintaining the regenerative and immune regulatory effect in the sense of the CARE® (Cell Activity Regeneration Effect) Technology .
Despite the history of more than 100 years, molecular and immunobiological research on health promotion using molecules separated biotechnologically from foetal/juvenile xenograft tissue and prepared in a GMP-compliant manner is still in its infancy.
Thanks to the help of the latest analysis and investigation methods, however, we better understand how health works in its complexity and how it can be actively promoted sustainably by therapeutic application of defined signaling and structural molecules.
The underlying biological principles are complex and multidimensional, but always fundamentally oriented towards the maintenance of internal homeostasis. The new findings could already open up the possibility of promoting individual resources in a targeted manner even in the sense of salutogenesis and counteracting the development of disease at early stages. Based on this, we strive for the further development of our GMP-compliant biotechnologically produced organ tissue preparations, towards drug-legally approved novel biologics with clearly defined medical indication and proven health-promoting properties.
 Jørgensen C.B.: A. A. Berthold, and the origins of endo-crinology. Odense University Press, 1971.
 Tshisuaka B.I.: Brown-Séquard, Charles Édouard. Enzy-klopädie Medizingeschichte. De Gruyter, Berlin/ New York 2005, S. 214.
 Tröhler U: Nobelpreisträger Theodor Kocher 1841–1917. Auf dem Weg zur physiologischen Chirur-gie. Basel/Boston/Stuttgart 1984; Neudruck Basel 2014..
 Murphy K, Weaver C. Janeway´s Immunobiology. 9th Revised edition. Garland Publishing 2016
 Wolf E. Vor 50 Jahren: Paul Niehans bringt den Begriff «Zellulartherapie» in die Öffentlichkeit. Schweizerische Ärztezeitung 2002;83:1726-1727
 Fischer KJ. Niehans. Arzt des Papstes. München, Wien: Andermann; 1957.
 Hofer HG. Arzneimittel des 20. Jahrunderts. 1957 –Frischzell-Fama. Paus Niehans und die westdeutsche Aufbaugesellschaft der 1950er Jahre. 2009
 Franks F. Freeze-drying of bioproducts: putting principles into practice. European Journal of Pharmaceutics and Biopharmaceutics 1998
 Schmid F et Stein J. Zellforschung und Zellulartherapie. Verlag Hans Huber Bern und Stuttgart. 1963
 Landsberger A. Zelltherapie – Complementärmedizin der Zukunft. COMED 2009;08:1-3
 Bennhold H. Die Gefahren der Zellulartherapie. Dtsch Med Wochenschr 1955;80(35):1262-63
 Schmid F. Cell Therapy: A New Dimension of Medicine. Thoune, Switzerland: Ott Publishers, 1983: 455.
 Landsberger A. Zur Frage der Wachstumshemmenden Funktion der Gewebemastzelle. Acta anat. 1966; 64: 245- 255..
 Landsberger et al. Tumorselektive Einschleusung cytostatischer Chemotherapeutika durch sulfatierte Glykosaminoglykane. TW Gynäkologie 1989;2:307-214
 Landsberger A., M. Drautz, U. Klement, S. Wagner: Verminderung zytostatisch bedingter Nebenwirk-ungen durch Zusatzbehandlung mit Resistocell® ; Cytobiol.Rev. 10, 3, S. 140-145 (1986)
 Blumenberg F.-W.: Erste klinische Erfahrungen über die Zusatztherapie mit einem Zellpräparat zur Strahlen- bzw. Zytostatika-Therapie; Die Heilkunst 84, 10, S. 287-289 (1971)
 Renner H., Kh. Renner: Die Therapie mit xenogenem, lyophilisierten Fetalgewebe als Adjuvans beim fortge-schrittenen Mammakarzinom; Akt.Onk. 32, S. 75-83, W. Zuckschwerdt, München Bern Wien (1986)
 Schmid H., M. Kaufmann, U. Abel, F. Kubli: Lyophili-siertes fetales Mesenchym (Resistocell) beim metas-tasierten Mammakarzinom - prospektiv randomisierte Studie; TumorDiagnostik&Therapie 10, S. 115- 118 (1989)
What can we do for you?
The cell and immune-regulative molecular therapy is based on fundamental scientific findings in biology, chemistry, physics, and medicine. That is why this therapy demands a profound and qualified education in this day and age.
Our basic seminars plus additional systems-specific courses ensure the correct application on the patient. The physician benefits from this specialisation with a new skillset, expertise and confidence. At the same time, our seminars form the basis for a therapy getting more and more positive attention; a therapy for the benefit of the patients.
All the basics are conveyed herein: diagnosis, pre- and follow-up-treatment of the application itself, distinction between humane and xenogeneic basis, etc. Further decidedly information and instructions for the fulfilment of the statutory requirements in Germany, the own-manufacture process, applications in practice plus medication of the various cell preparations and aftercare.
Detoxification therapies, metabolism diagnostics, measurement parameters of the regulatory levels, peripheral applications (ozone, oxygen multi-step therapy, base infusions, etc.), specific indication-based case studies and follow-on treatments.
Allows all physicians to attend further training courses such as mesotherapy, emergency medicine, pain therapy (also qualifies for education points within the framework of the German points system for a physician's continuous training).
Cell Immun is accompanying you in the application of the cell therapy inter alia in the form of injectable tissue suspensions and cell peptides through oral intake. These preparations are in their intensity and bioavailability many times over what normal food can offer. Permanent quality checks guarantee the exceptional level of the products. Educated cell therapists are focussing on medicating the underlying causes and fine-tune the treatment in collaboration with their patients.
A respectable cell therapy consists of a comprehensive medical history plus accompanying therapies like e.g. conventional treatment methods, additional naturopathic treatments and/or physiotherapy. Depending on the service package you (can) select, you will get extensive access to our international team of experts with decades of professional experience in these medical matters.