Day 1 :
Keynote Forum
Richard George Pestell
Pennsylvania Cancer and Regenerative Medicine Research Center, USA
Keynote: CCR5 governs stem cell characteristics, therapy resistance and metastasis of breast cancer
Time : 09:00-09:45
Biography:
Richard George Pestell completed his MBBS and subsequently PhD, MD (Melbourne University) FRACP, FACP, MBA (NYU) with Post Doctoral studies at Harvard University and Massachusetts General Hospital. He was Director of the Lombardi Comprehensive Cancer Center (2002-2005), the Sidney Kimmel Cancer Center (2005-2015) and most recently Executive Vice President of Thomas Jefferson University. He is the author of over 620 published works and 36 books and chapters, with over 50,000 citations, H index 121. He served and or serves on 14 scientific journal editorial boards, external advisory boards of 7 NCI cancer centers, several international research institutes, and review boards for research funding agencies of USA, Italy, UK, Switzerland, Ireland, France, Israel, Australia, and Czech. He is the Founder of two biotechnology companies, and has multiple issued patents.
Abstract:
Recent studies have demonstrated a propensity of tumor initiating cells with stem cell-like features to contribute to metastasis and therapy resistance. The mechanisms by which cancer stem cells survive chemotherapy- and radiotherapy is not well understood. We herein describe the novel finding that the immune chemokine receptor CCR5 is selectively expressed on transformed breast epithelial cells, promoting breast cancer stem cell expansion and DNA damage repair. Reintroduction of CCR5 into CCR5-negative cells promoted breast tumor stem cell expansion, metastases, and the induction of DNA repair gene expression. CCR5 was shown to enhance the repair of Double Stranded DNA Breaks (DSBS) by inducing HDR and SSA-based DNA repair. Single cell sequencing documented activation of gene expression pathways mediating ribosomal biogenesis and cell survival in CCR5+ cells. In a broad array of BRCA1mutant breast cancer cell lines DNA damaging chemotherapeutic agent-mediated cell killing was dramatically enhanced by CCR5 antagonists. Because CCR5 is expressed only on the breast cancer epithelial cells the current findings illustrate CCR5 inhibitors enhance the tumor specific activities of DDR-based treatments.
Keynote Forum
Roohi S Ahmad
Universiti Putra Malaysia, Malaysia
Keynote: RGTA based Matrix therapy for wound healing and tissue regeneration in Hand Surgery
Time : 09:45-10:30
Biography:
Roohi completed her basic medical and Master’s degrees in Orthopaedic Surgery from National University of Malaysia and is presently holding a tenured post in Universiti Putra Malaysia. She has more than 2 decades of surgical experience and practising rights in four countries. She has published more than 40 papers in reputed journals and is presently working on stem cell applications in bones and soft tissues.
Abstract:
ReGeneraTing Agents (RGTAs) are a family of polymers bioengineered to stabilise heparin-binding growth factors by mimicking Heparan Sulphate (HS) thereby protecting them and promoting tissue repair and regeneration. In inflammation, destruction of HS exposes the ExtraCellularMatrix – ECM (structural & cellular proteins within) to the actions of proteases and glycanases which break them down and also act on cytokines and growth factors to prevent adequate repair. In injured tissue, RGTAs would replace destroyed HS by binding to the structural proteins and reconstruct the ECM scaffold. Growth factors will also bind to RGTA and resume position and organization resembling that of non-injured tissue. Hence RGTAs showed they induce a regeneration process by restoring the proper cellular micro-environment. More recently a RGTA named CACIPLIQ20 was adapted to skin lesions and has shown efficacy in various trials of non-healing leg ulcers.
We extrapolated this action to human tissue (of poor vascularity) and applied the same RGTA with meticulous wound care techniques on 15 patients with wounds of varying sizes and depths in the upper limb. We observed that the wounds healed or granulation tissue grew again where there was dead skin and no visible underlying blood supply which in usual circumstances would have resulted in loss of limb length, dry gangrene or at best healing by severe scarring. Exposed tendons were also covered with granulation tissue, and resulted in a fair range of motion. Full thickness palmar and dorsal wounds also healed beautifully reproducing a flexible movable dorsal surface not seen in granulating, scarred healing.
Keynote Forum
Roohi S Ahmad
Universiti Putra Malaysia, Malaysia
Keynote: RGTA based Matrix therapy for wound healing and tissue regeneration in Hand Surgery
Time : 09:35-10:10
Biography:
Roohi completed her basic medical and Master’s degrees in Orthopaedic Surgery from National University of Malaysia and is presently holding a tenured post in Universiti Putra Malaysia. She has more than 2 decades of surgical experience and practising rights in four countries. She has published more than 40 papers in reputed journals and is presently working on stem cell applications in bones and soft tissues.
Abstract:
ReGeneraTing Agents (RGTAs) are a family of polymers bioengineered to stabilise heparin-binding growth factors by mimicking Heparan Sulphate (HS) thereby protecting them and promoting tissue repair and regeneration. In inflammation, destruction of HS exposes the ExtraCellularMatrix – ECM (structural & cellular proteins within) to the actions of proteases and glycanases which break them down and also act on cytokines and growth factors to prevent adequate repair. In injured tissue, RGTAs would replace destroyed HS by binding to the structural proteins and reconstruct the ECM scaffold. Growth factors will also bind to RGTA and resume position and organization resembling that of non-injured tissue. Hence RGTAs showed they induce a regeneration process by restoring the proper cellular micro-environment. More recently a RGTA named CACIPLIQ20 was adapted to skin lesions and has shown efficacy in various trials of non-healing leg ulcers.
We extrapolated this action to human tissue (of poor vascularity) and applied the same RGTA with meticulous wound care techniques on 15 patients with wounds of varying sizes and depths in the upper limb. We observed that the wounds healed or granulation tissue grew again where there was dead skin and no visible underlying blood supply which in usual circumstances would have resulted in loss of limb length, dry gangrene or at best healing by severe scarring. Exposed tendons were also covered with granulation tissue, and resulted in a fair range of motion. Full thickness palmar and dorsal wounds also healed beautifully reproducing a flexible movable dorsal surface not seen in granulating, scarred healing.
- Gene and Cell Therapy| Epigenetics and Stem Biology
Location: Conference Hall
Session Introduction
Karin Schutze
CellTool GmbH, Germany
Title: Lights on - Raman approach in stem cell research and medicine
Time : 10:30-11:00
Biography:
Karin Schuetze is a Biologist and expert in non-contact cell handling and label-free cell analysis using innovative photonic technologies. She did her PhD work at the Institute for Applied Physical Chemistry in Heidelberg and her Postdoc Research at the University of California in Berkeley where she assembled her first Optical Trap. In 1993 she and her husband founded the PALM company, which was successfully sold to Zeiss. In 2008, they both founded their second company, the CellTool GmbH, where they develop Raman microscope systems for biomedical applications, providing physicians and biologists with a label-free and non-invasive tool for cell analysis.
Abstract:
In the last years, the field of stem cell medicine has opened unforeseen therapeutic opportunities. In order to ensure functionality and safety of cell based therapies used for patient care, methods allowing reliable quality control during all steps of product development are essential. Raman Spectroscopy (RS) is a highly sensitive technology increasingly used for biomedical applications like cell identification, diffentiation and characterization, as well as quality control of cell based products as it reveals detailed information on the metabolic state of living single cells in a label-free and non-invasive way. Here, we demonstrate that RS is a valuable tool also in stem cell research and medicine. It helps to understand basic cellular processes, to ensure quality of cell based products and to improve current gold standard methods. We provide latest data from Raman analyses of single cells as well as of 3D cell culture and tissues, including investigations on retina tissue, insights on the influence of stem cell freezing and quality control of chondrocytes and blood products, showing that this non-invasive approach provides new insights on the whole metabolome of cells which help to improve and secure approaches in stem cell medicine.
Francisco Ruiz-Navarro
Austrian Society for Regenerative Medicine, Austria
Title: Developing clinical guidelines to treat neurological and neurosurgical disorders with stem cells
Time : 11:00-11:30
Biography:
Francisco Ruiz-Navarro is a Research Associate and R&D Director of the Austrian Society for Regenerative Medicine in Vienna, Austria where he focuses his research in stem cell therapies for neurological disorders. Before, he was performing research in the Cerebrovascular Department at the National Institute for Neurology and Neurosurgery in Mexico City with special interest in multicentric population studies with Hispanic stroke patients. He was a Research Assistant in the Brain Bank, Center for Research and Physiology, Department of Biology and Neuroscience at the Institute of Advanced Studies at National Polytechnic Institute in Mexico City. He obtained his Medical degree in the Anahuac University in Mexico City, became USMLE board certified in the United States of America and he got his Doctor of Medicine from the Medical University of Vienna.
Abstract:
After reviewing several current clinical guidelines, we found that less than 1% of all the recommendations for neurological diseases in the clinical guidelines are sustained by a level 1A of evidence (Systematic review of RCT with homogeneity, according to the Oxford Centre of Evidence). When reviewing the scientific evidence of stem cells treatment, we found that several stem cell therapies are based on the same or even stronger scientific evidence than the current medical treatment. This means accepted treatments and stem cell treatments nearly have the same level of evidence. Although both are far from level A, it is apparently enough for several clinicians and regulatory agencies to maintain a reluctant posture towards stem cell therapies but not towards other kinds of treatment. We propose that not just level 1A of evidence should be accepted as treatment, especially in cases where there are no options for patients besides experimental treatments. In this debate, the necessity of RCT or blinded trials arises, especially because SCs therapies are a procedure rather than medication and conducting clinical studies with “surgical placebos” is ethically controversial. There are analyses that describe how series of observational studies found results similar to those obtained from RCTs, which means that certain number of cohort or case-control studies would yield enough valuable information to bring treatments to the clinical practice, although we plan to wait for better-design RCT to confirm the results, if possible. We reviewed the most relevant literature concerning the use of stem cells to treat several neurological disorders. This literature review will provide key information on how stem cell’s interventions were performed with the analysis of the level of evidence they are providing. Drawing on the gathered information we then compared the scientific evidence that underlies the current treatment guidelines with the scientific evidence on currently available stem cells publications. As a result of this survey and analysis we conclude with a series of recommendations for the use of stem cells in clinical settings.
Michał Pikuła
Medical University of Gdansk, Poland
Title: Phenotypic and functional analysis of human adipose-derived stem cells
Time : 11:30-12:00
Biography:
MichaÅ‚ PikuÅ‚a is an Associate Professor at the Department of Clinical Immunology and Transplantology, Medical University of Gdansk. He has completed his MPharm from Medical University of Gdansk (Pharmacy Practice), MSc from University of Gdansk (Molecular Biology) and his PhD in Medical Biology from Medical University of Gdansk (Faculty in Medicine) in 2007. He is currently responsible for several projects focused on Regenerative Medicine and Experimental Immunology. He is also a Group Leader in a prestigious REGENNOVA consortium grant STRATEGMEDI (“Novel Technologies for Pharmacological Stimulation of Regeneration”).
Abstract:
Human adipose tissue constitutes a rich source of multipotent stem cells. Adipose-derived Stem Cells (ASCs) have been in the center of scientific and clinical attention, due to a wide range of possible implementations in tissue engineering, regenerative medicine and clinical immunology. These cells are characterized by a multipotent activity including high proliferative potential, secretion of trophic factors, direct interactions with immune cells and ability to differentiate into different kind of cells. Despite being extensively studied, phenotypic characterization of specific surface markers and details of differentiation potential need to be elucidated. The data obtained in our studies, based on flow cytometry technique, show that ASCs cultured in vitro express elevated levels of ASCs markers typical for mesenchymal stem cells (CD73, CD90, CD105, CD29). The variable level of expression was observed for CD31 and CD34, what seems to be a donor-to-donor variability. The observed markers expression did not affect the differentiation capacity of ASCs into chondrocytes, adipocytes and osteocytes. Additionally, our results show that the long term in vitro culture of ASCs has no impact on the surface expression markers pattern. According to our observations, no significant differences in the surface markers level and differentiation potential were noted between the cells obtained from oncological patients or from plastic surgery procedures. Summarizing, our studies reveal that ASCs are a promising tool in postoperative tissue reconstruction in oncological patients due to their high regenerative potential. However, further studies are required to provide more insight into the therapeutic potential of ASCs in postoperative management of patients undergoing oncology surgery.
Vassilis Katsares
Embryolab IVF Unit, Greece
Title: Stem cells: A ray of hope for treating infertility
Time : 01:00-01:30
Biography:
Vassilis Katsares is a Biologist with a PhD on Populational Molecular Genetics. He completed three Postdoctoral Fellowships. He also served as a lecturer for undergraduate and postgraduate courses. He had worked as Technical Sales Support for immunology analyzers and afterwards he was the Laboratory Director at a biopharmaceutical company. His main research interests cover many aspects of Molecular Genetics, Cellular Therapy projects, and bioethics. He has authored 21 scientific papers and 36 announcements at national and international conferences. He is a referee in various journals. He is member in many international Scientific Organisation and Societies. His CV is included in “Who is Who in the World”, and in “Who is Who in Science and Engineering”.
Abstract:
Stem cells play a significant role in the novel branch of modern Biology and Medicine, known as Regenerative Medicine. Due to their regenerative ability, stem cells are looked at as a promising tool for improving infertility treatments in women and men. It has been shown that fully mature egg cells, as well as sperm cells can be grown in the lab, raising hope for new infertility treatments. There has been also evidence that eggs could be fertilised, implanted into a surrogate female and go on to produce live offspring. All the obtained offspring grew up normally without evidence of premature death. Artificially created sperm and eggs could spell the end of infertility at the near future. Stem cells can potentially be developed into any tissue in the human body. Reproductive scientists think it is only a matter of time before the technique is used as an alternative IVF treatment. Nowadays, there is also the new trend of ovarian rejuvenation, using stem cells growth factors to improve the ovulation of older ovaries. However, for all these techniques to become a clinical reality, many potential risks and ethical concerns about the use of stem cells must first be addressed. If the treatment works, it could be extended to even older post-menopausal women. Should the law review the ceiling on how old a woman can be to have this treatment since there is no law stopping a man from having a child late in life? All this research may alter our understanding of male and female infertility and provide solutions to IVF treatments. Though a long way off, if ever, it would be an incredible change in how we view and treat infertility.
Joseph Choukroun
Pain Clinic, France
Title: Extraction of blood mesenchymal stem cells with the low speed centrifugation concept: Applications in regenerative medicine
Time : 12:30-01:00
Biography:
Joseph Choukroun completed MD from University of Montpellier, France 1979 and is a Specialist in General Surgery, Anesthesiology from the same university. He is also a Specialist in Pain Management from University of Strasbourg France. He is the Owner of Private Pain Clinic, Nice France. He is the President of SYFAC, international symposium on growth factors. He is the Inventor of the PRF techniques: L-PRF, A-PRF and i-PRF. He is a Researcher working in Form Lab at University of Frankfurt. He is the author of several scientific publications and is recognized as an International Speaker.
Abstract:
Regenerative therapy with stem cells has gained tremendous momentum over the past decade as a modality geared towards markedly improving wound healing of various tissues by utilizing undifferentiated autologous host cells. While stem cells may be isolated from various locations in the human body, more recently it has been shown that low levels of mesenchymal stem cells also exist circulating within peripheral blood. Platelet rich fibrin (PRF) is a regenerative modality that utilizes peripheral blood + centrifugation protocols without the use of anti-coagulants to create a three-dimensional tissue engineering scaffold containing both growth factors and autologous cells. Very recently, it has been shown that modifications to centrifugation speed and time following recently developed concepts (the low-speed centrifugation concept or LSCC) resulted in a marked increase in host cells and growth factors. Within these scaffold constructs, mesenchymal stems cells were also found following collection with this relatively painless and low-cost modality. The objective of the present talk will be to present recent modifications to centrifugation speed and time to optimize stem cell quantities within PRF. Thereafter, the biological data supporting their numbers, as well as their potential for clinical applications will be presented with data coming from many fields of medicine including for the regeneration of osteoarthritic knees, dental regenerative medicine, orthopedic grafting, and for facial esthetics.
Simon Haas
German Cancer Research Center (DKFZ), Germany
Title: : Human hematopoietic stem cell differentiation follows a continuous Waddingtonlike landscape
Time : 02:00-02:30
Biography:
Simon Haas is Group Leader at the Heidelberg Institute for Stem Cell Technology and Experimental Medicine and the German Cancer Research Center. He is an expert in hematopoiesis, with a special focus on stem cell biology. His research centers around the question how hematopoietic stem cells make complex lineage decisions to produce the variety of blood and immune cells.
Abstract:
Multipotent hematopoietic stem cells are responsible for the livelong production of all blood and immune cells. In the classical model of hematopoiesis, blood formation is believed to occur through stepwise progression of hematopoietic stem cells following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on experimental approaches unable to describe how individual HSCs and their progeny enter lineage commitment during steady-state hematopoiesis. To establish a comprehensive model of human hematopoiesis, we have developed single-cell approaches that integrate single-cell RNA-sequencing with flow cytometric and functional lineage potency data. This allows us to reconstruct developmental trajectories and to gain a detailed view on lineage commitment of individual HSCs into all major branches of human haematopoiesis. We found that individual HSCs do not pass through discrete intermediate progenitor cell stages. In contrast, HSC lineage commitment occurs in a gradual manner best described by a continuous Waddington landscape with initially flat but progressively deepening valleys. Our data determine a detailed model of developmental trajectories within this landscape and demonstrates that distinct gene expression modules operate in a combinatorial manner to control stemness, early lineage priming and the subsequent progression into all major branches of hematopoiesis. These results establish the concept of a developmental continuum, which can replace the differentiation tree as a comprehensive model of human steady-state hematopoiesis and provide a basis for the understanding of hematopoietic malignancies.
Lenger Karin
Institute for Scientific Homeopathy, Germany
Title: Institute for Scientific Homeopathy, Germany
Time : 02:30-03:00
Biography:
Lenger Karin Dr.rer.nat., pursued Diploma in Biochem, studied Biochemistry at the Universities of Tubingen and Cologne. Her research topics revolved around enzymatic gene regulation, cancer research, enzymatic mechanisms of steroid hormones at the Medical University of Lubeck. In 1987 she became a Lecturer for Homeopathy at DHU ((Deutsche Homöopathie Union = German Homeopathy Union). Since 1995 she worked as a Homeopathic Practitioner and developed the “biochemical homeopathy” by using highly potentized substrates of pathological enzymes for her patients. She detected magnetic photons in high homeopathic potencies by two magnetic resonance methods and developed a model of physical and biochemical function of homeopathy.
Abstract:
Karin Lenger detected magnetic photons in highly diluted and potentized homeopathic remedies. Since the living body is an electromagnetic wavepackage (Einstein), the homeopathic law of Similars (Hahnemann 1755-1843) can be expressed as: the frequencies of the patient must match the frequencies of the remedies. Homeopathy is a regulation therapy curing hypo and hyperfunction of a pathological pathway by resonance: highly potentized substrates, inhibitors, enzymes, receptors of the distinct pathological pathways cure according to biochemical rules: A homeopathic symptom picture is obtained by poisoning a volunteer with a toxin. Simultaneously he develops psychological symptoms, the toxicological pathway and e.g. frequencies I-V. The highly potentized toxin has the frequencies I-V. The patient has symptoms as if he was poisoned by the toxin: during his illness he developed the toxicological pathway, frequencies I-V and psychological symptoms. The potentized toxin cures simultaneously the patient’s frequencies by resonance, his pathological pathway and the psychological symptoms. A stitch of honey bee, apis mellifica, causes a red oedema; a patient developing a red oedema at the finger-joint by rheumatism is cured by highly potentized Apis mellifica. Paralyses caused by a lack of the neurotransmitter acetylcholine bound to the acetylcholine-receptor at the post-synapsis can be healed by using these potentized remedies: the venom of cobra, Naja tripudians containing the receptor’s irreversible inhibitor cobrotoxin, the reversible inhibitor Atropine and Acetylcholine, daily applied. The availability of acetylcholine is maintained by glycolysis and fatty acid oxidation. This can be supported by giving these remedies: Lecithin, Lipasum, Glycerinum, Glucosum and Coenzyme A.
Joseph Choukroun
Pain Clinic, France
Title: Extraction of blood mesenchymal stem cells with the low speed centrifugation concept: Applications in regenerative medicine
Time : 09:00-09:30
Biography:
Joseph Choukroun completed MD from University of Montpellier, France 1979 and is a Specialist in General Surgery, Anesthesiology from the same university. He is also a Specialist in Pain Management from University of Strasbourg France. He is the Owner of Private Pain Clinic, Nice France. He is the President of SYFAC, international symposium on growth factors. He is the Inventor of the PRF techniques: L-PRF, A-PRF and i-PRF. He is a Researcher working in Form Lab at University of Frankfurt. He is the author of several scientific publications and is recognized as an International Speaker.
Abstract:
Regenerative therapy with stem cells has gained tremendous momentum over the past decade as a modality geared towards markedly improving wound healing of various tissues by utilizing undifferentiated autologous host cells. While stem cells may be isolated from various locations in the human body, more recently it has been shown that low levels of mesenchymal stem cells also exist circulating within peripheral blood. Platelet rich fibrin (PRF) is a regenerative modality that utilizes peripheral blood + centrifugation protocols without the use of anti-coagulants to create a three-dimensional tissue engineering scaffold containing both growth factors and autologous cells. Very recently, it has been shown that modifications to centrifugation speed and time following recently developed concepts (the low-speed centrifugation concept or LSCC) resulted in a marked increase in host cells and growth factors. Within these scaffold constructs, mesenchymal stems cells were also found following collection with this relatively painless and low-cost modality. The objective of the present talk will be to present recent modifications to centrifugation speed and time to optimize stem cell quantities within PRF. Thereafter, the biological data supporting their numbers, as well as their potential for clinical applications will be presented with data coming from many fields of medicine including for the regeneration of osteoarthritic knees, dental regenerative medicine, orthopedic grafting, and for facial esthetics.