The use of autologous cell therapy for treatment of cardiac disease

Transcription

1 The use of autologous cell therapy for treatment of cardiac disease IET Present Around The World Competition London, 9 th Nov Representing EMEA Theodora Chrysostomou

2 Overview Autologous stem cell therapy Not allogeneic based therapy possibility of immune rejection Results prove high potential to regenerate damaged myocardium Yet no solid treatment in the market 2 Comparison of experiments under various conditions

3 Aim Analyse experiments to observe the most favourable conditions for treating cardiovascular diseases (CVDs) using stem cell therapy. Target market is based on facts, as CVDs remain the leading cause of morbidity & mortality globally. A third of global deaths 3

4 Target market 4 Percentage breakdown of deaths from cardiovascular diseases

5 The Myocardium Heart anatomy Source: Waugh&Grant (2006) 5 Number of myocytes undergoing proliferation is low compared with other tissues that have high levels of cellular regenerative capacity.

6 What stem cells are Unspecialised cells Can undergo self-renewal Can differentiate into specialised cells 6 Centre of new field of science Regenerative medicine through engineering cells

7 Main types of stem cells Embryonic stem cells (ESCs) (pluripotent) Adult stem cells (ASCs) (multipotent) Isolated from the embryo Fertilised in-vitro Isolated from adult somatic tissue found in the body after birth 7 Cultured and inserted back into the patient

8 Stem cell divides Remain a stem cell Become a different type of cell with a more specialised function (i.e. red blood cell, brain cell, muscle cell) 8 BUT ASCs produce a limited number of the target cell types have a more limited differentiation potential

9 Transdifferentiation of ESCs into cardiovascular phenotype. 9 Following fertilised the inner mass from the blastocyst can be cultured ex-vivo to form multiple cardiovascular cell types. legal & ethical constraints Source M.J. Lovell & A. Mathur (2004)

10 Nevertheless ASC biology is the forefront of the emerging field of regenerative medicine tissue engineering Offering a source of cells to generate tissues that lack some of the ethical & political impediments inherent in embryonic, fetal & cloned cells. 10 Fewer problems with immune rejection & pathogen transmission

11 Method used Adult stem cells extracted from patient Cultured in laboratory Self renewal through cell division: Allowed to differentiate & proliferate (to create required amount), under correct environmental signals/conditions Implanted back into patient 11 Follow-up

12 12 Process route using BMMNCs scale-out to some extent

13 Methods: Identification of stem cells Label cells with molecular markers Stained cells in culture 13 Removing cells from living tissue (animal/human) Label them in cell culture & transplant back into another tissue Determine whether the cells replace their tissue of origin & can generate a line of genetically identical cells

14 Cell therapy provides hope Promising pre-clinical studies on animal models successful safety & efficacy tests Interpretation of experimental data is difficult No precise comparison numerous factors affecting trials 14

15 Results: Animal Studies for myocardial infarction using stem cells in LAD (Left anterior descending artery) ligation induced models Animal model Treatment Results Mice Orlic et al.2001 Jackson et al.2001 Mangi et al Bone Marrow -MSCs -Direct epicardial injection -After MI - ~ cells Up to 68% of infarct engrafted with transplanted cells Increase in survival by increased wall thickness & improved EF 80-90% regeneration of myocardium using MSC Dogs Hamano et al >> Improved wall thickening Proved safety & efficacy of BMC implantation for ischemic heart disease Higher nerve density 15 Pigs Pak et al Shake et al >> Significant increase in systolic function Higher nerve density

16 Results: Clinical Studies for patients with Acute Myocardial Infarction using autologous BMMNCs Treatment: Unhealthy & control subjects Phase I, II, III ~10 6 cells Percutaneous intracoronary transplanted few days after injury Outcome: Ventriculography assessed reduced infarct size & increased infarct wall movement velocity, improvement in LV ejection function Improved diastolic function shown by MRI Only for a limited amount of time 16 Some studies: BOOST; Wollert et al. 2004; TCT-STAMI Ge et al.2006; REPAIR-AMI Cleland et al.2006

17 Unfavorable Clinical Studies for patients with Acute Myocardial Infarction using BMMNCs No significant improvement in LVEF No effect on infarct size Injection of BMC is not safe for some patients as they had higher incidence of in-stent restenosis (9/19) No significant improvement in cardiac function 17 Some studies: - Valgimigli et al Bartunek et al MAGIC Cell-3-DES (Kang et al. 2006) - STEMMI (Engelmann et al. 2006) - REVIVAL-2 (Zohlnhofer et al. 2006) - Janssens et al Penicka et al. 2007

18 Conclusion Animal pre-clinical studies: More promising Faster development Compared to human clinical trials Autologous BMSCs : Safely administered for AMI Evidence of cardiac regeneration 18 Obstacle: Finance Decide: which stem cell type to use, cell fate, cell modifications, identify the mechanisms by which stem cells promote myocardial function, feasible delivery methods & all the safety issues

19 Future work More studies with less variation between one another Allow free use of stem cell therapies Global collaboration amongst scientists 19

20 Thank you for your attention 20 It s nothing that a few stem cells & 75 years of research can t fix

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