Author Interviews, Heart Disease, Stem Cells / 15.03.2016
Using Small Carriers Increases Number of Cardiac Stem Cells Remaining in Heart
MedicalResearch.com Interview with:
[caption id="attachment_22678" align="alignleft" width="90"]
Dr. Joost Sluijter[/caption]
Joost P.G. Sluijter, PhD, FESC
Associate Professor
Department of Cardiology
Experimental Cardiology Laboratory
UMC Utrecht
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sluijter: Cell transplantation therapy for ischemic heart disease has entered the arena of clinical trials more than a decade ago. Multiple cell types have been used since these first endeavors, and there is accumulating evidence that different cell types positively influence the damaged heart through paracrine and/or regenerative mechanisms. One of the most promising cell types to be used are the cardiac-located stem cells. Cardiac stem cells (CSCs) have been found to reside in the adult heart and can differentiate towards all cell types that are needed in the normal functional heart. These cells have shown great potential as a regenerative therapeutic upon myocardial infarction (MI) in animal models and are currently being tested in some clinical studies. However, although promising, no systematic overview and subsequent meta-analysis of preclinical data exists to date for this cell type and if they are consistently effective. Our systematic approach, yielded 80 studies and included over 1900 animals, confirms the consistent effect of CSCs and provides us with a first comprehensive overview of pre-clinical MI studies in an unbiased and systematic manner. Nowadays we are aware of a failure in therapeutic effect size for the translation axis, where we try to bridge fundamental findings from the lab to the bedside. This means that effects we observe in our initial studies on cardiac performance are slowly getting less successful when we are getting closer to a real clinical scenario.
Through our meta-analysis, we observed a consistent therapeutic effect of Cardiac stem cells therapy on cardiac function after MI, where 12% of functional improvements is observed in rodents, and only an 8% improvement was still present in large animal models. From previous observations, we know that this leaves a 3-4% of effect in a patient population. In addition to the difference in effect size between small and large animal models, also a difference in study quality and attrition bias was observed. Interestingly, although additional support to the idea that Cardiac stem cells are efficacious in preclinical studies were observed, we did not find any influence of immunosuppression, cell source, comorbidity of CSC donors, culture methods, or model of ischemia on the outcomes.
Dr. Joost Sluijter[/caption]
Joost P.G. Sluijter, PhD, FESC
Associate Professor
Department of Cardiology
Experimental Cardiology Laboratory
UMC Utrecht
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sluijter: Cell transplantation therapy for ischemic heart disease has entered the arena of clinical trials more than a decade ago. Multiple cell types have been used since these first endeavors, and there is accumulating evidence that different cell types positively influence the damaged heart through paracrine and/or regenerative mechanisms. One of the most promising cell types to be used are the cardiac-located stem cells. Cardiac stem cells (CSCs) have been found to reside in the adult heart and can differentiate towards all cell types that are needed in the normal functional heart. These cells have shown great potential as a regenerative therapeutic upon myocardial infarction (MI) in animal models and are currently being tested in some clinical studies. However, although promising, no systematic overview and subsequent meta-analysis of preclinical data exists to date for this cell type and if they are consistently effective. Our systematic approach, yielded 80 studies and included over 1900 animals, confirms the consistent effect of CSCs and provides us with a first comprehensive overview of pre-clinical MI studies in an unbiased and systematic manner. Nowadays we are aware of a failure in therapeutic effect size for the translation axis, where we try to bridge fundamental findings from the lab to the bedside. This means that effects we observe in our initial studies on cardiac performance are slowly getting less successful when we are getting closer to a real clinical scenario.
Through our meta-analysis, we observed a consistent therapeutic effect of Cardiac stem cells therapy on cardiac function after MI, where 12% of functional improvements is observed in rodents, and only an 8% improvement was still present in large animal models. From previous observations, we know that this leaves a 3-4% of effect in a patient population. In addition to the difference in effect size between small and large animal models, also a difference in study quality and attrition bias was observed. Interestingly, although additional support to the idea that Cardiac stem cells are efficacious in preclinical studies were observed, we did not find any influence of immunosuppression, cell source, comorbidity of CSC donors, culture methods, or model of ischemia on the outcomes.
Prof. Dimitrios Karussis[/caption]
MedicalResearch.com Interview with:
Prof. Dimitrios Karussis M.D., Ph.D.
Professor of Neurology
Head, Multiple Sclerosis Center
Hadassah BrainLabs
Medical Research: What is the background for this study? What are the main findings?
Prof. Karussis: BrainStorm Cell Therapeutics is developing innovative, autologous stem cell therapies for highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD). Our technology, NurOwn™ is a first-of-its-kind approach that induces autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) to secrete Neurotrophic Growth Factors (NTFs). These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases.
Data from the clinical trials described in the recent issue of the Journal of American Medicine – Neurology (JAMA Neurology), suggest that NurOwn can help patients with 
Dr. Jenny C. Chang[/caption]
MedicalResearch.com Interview with:
Jenny C. Chang, M.D.
Director, Houston Methodist Cancer Center
Professor of Medicine, Weill Cornell Medical College
Full Member, Houston Methodist Research Institute
Houston, Texas
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Chang: The current treatment of triple negative breast cancer, which accounts for about 15% of all cases of breast cancer, is still based on surgery, radiotherapy, and classic chemotherapy because, unlike other types of breast cancer, it is not amenable to hormonal or targeted therapy. However, research findings suggest that cancer stem cells, which represent about 2% of all neoplastic cells, may play a role in disease relapses and the formation of distant metastases. As these cells may represent a therapeutic target, the aim of this study is to modify the micro-environment in which they reproduce by acting directly on the chemokines involved in inflammation because there is evidence indicating a possible mechanism of action of reparixin, a molecule developed by Dompé, an Italian biopharmaceutical company, in the targeted treatment of these cancers.
Dr. Chris Hawkey[/caption]
MedicalResearch.com Interview with:
Dr. Chris J. Hawkey, DM, FRCP, FMedSci.
University of Nottingham and Nottingham University Hospital
England
Medical Research: What is the background for this study?
Dr. Hawkey: ASTIC (The Autologous Stem Cell Transplantation International Crohn's Disease) systematically investigated the effect of immunoablation and autologous haemopoietic stem cell transplantation (HSCT) on objective signs of disease, symptoms and need for treatment and is the only controlled trial to have done so. The body’s immune system normally protects us from infections but in Crohn’s disease it turns on itself. The treatment involves wiping out the body’s immune system (immunoablation) and replacing it with the patient’s own (autologous haemopoietic stem cell transplantation) innocent stem cells, a sort of immunological spring clean. Patients were randomly assigned to undergo transplantation (n=23) or just continue on best conventional treatment (n=22).
ASTIC was stimulated by reports which suggested that long-term regression of disease amounting to potential cure could be achieved. But the treatment is hazardous with major potentially lethal risks, so recruitment to the trial was cautious and only the most resistant cases were studied. And we used the most stringent criteria ever developed for the trial’s primary endpoint.
Medical Research: What are the main findings?
Dr. Hawkey: In fact the criteria we used for success were so stringent (no symptoms, no signs of disease on total bowel examination and no need for treatment) that few patients achieved them. Nevertheless, there were improvements in the individual measures underlying this composite endpoint. Objective signs of disease disappeared so that the gut looked normal from mouth to anus in about a quarter of actively treated patients vs no controls. Eight vs two patients were adjudicated free of active disease on endoscopy and radiology at final assessment (p=0.054). Patients were able to come off drug treatments: by the end of a year 61% of HSCT patients off immunosuppressive drugs for >3 months vs 23% of controls (p=0.012). Ten vs two patients had lost symptoms of active disease, eight vs two for of them for > 3 months (p=0.052).
But treatment was challenging: there were 76 serious adverse events in HSCT patients (particularly infections) vs 38 in controls. One HSCT patient died.
