AGING PROCESS FROM SYSTEM BIOLOGY CONCEPT Implication for Predictive, Preventive, Personalized and Participatory Medicine

REGENERATIVE MEDICINEIRAWAN YUSUFFaculty of Medicine Hasanuddin University

INTRODUCTION Diseased, degenerating or damaged organs and tissues give rise to a wide range of chronic illnesses. Patients suffering from such illnesses are currently faced with a relatively short list of options, include:long-term drug therapy, which may allow a disease to be managed but rarely cures it;organ transplant (there is a shortage of donor organs);medical devices such as pacemakers.

INTRODUCTIONRegenerative medicine aims to restore the function of tissues and organs by a variety of approaches. The idea is not new; the first bone marrow transplant took place in 1956, to treat a young boy suffering from leukaemia.In the 1956, bone marrow transplant from the patients identical twin. By the late 1960s and early 1970s, they were able to match donor tissues to patients by tissue typing. Much of the recent interest in regenerative medicine arises from developments in stem cell research, but there are also promising possibilities in biomedical and tissue-engineering.

THE GOALTo create products that improve tissue function or heal tissue defects.Replace diseased or damaged tissueBecauseDonor tissues and organs are in short supplyWe want to minimize immune system response by using our own cells or novel ways to protect transplant.

Regenerate, repair and replaceRegenerateIdentify the cues that allow for regeneration without scarringLike growing a new limbRepairStimulate the tissue at a cell or molecular level, even at level of DNA, to repair itself.ReplaceA biological substitute is created in the lab that can be implanted to replace the tissue or organ of interest5

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TYPES OF REGENERATIVE MEDICINECell Therapies:Therapy using a patients own cellsTherapy using cells from another personTissue Engineering.Biomedical Engineering.Gene Therapy.

Cell-based therapiesAimed at certain diseasesUses mostly only cells and no materialsType I diabetes transplant of new pancreas cellsAdult stem cells for heart diseaseNeuronal transplants for Parkinsons diseaseBone marrow transplant for various blood cancersMuscular dystrophy and polio

Tissue EngineeringTissue engineering involves modifying cells or tissues in some way so that they can repair, regenerate or replace tissue in the body.Using well designed scaffolds and optimized cell growth, we can create tissues such as:SkinBoneCartilageIntestineThese have been successfully engineered to some extent

Tissue-engineered products contain mixtures of the following:Biological components - cellsCan be genetically modified to behave a specific wayChemicals that tell the tissue to regenerate

Biomedical EngineeringBiomedical devices that mimic the function of a tissue or organ.A non-biological componentPolymer scaffoldFibers, plastic, other natural componentsGels

CELL THERAPY FOR CARDIOVASCULAR DISEASESCoronary artery diseases:Refractory angina (Baxter CD 34+; Acute myocardial infarction with left ventricular dysfunction;Heart failure.Ischemic stroke.Non-ischemic cardiomyopathy.

CELL THERAPY FOR CARDIOVASCULAR DISEASESIn patients with refractory ischemia, the goal is to improve coronary blood flow by promoting angiogenesis. The largest experience is with circulating CD34+ cells, and study is ongoing with intramyocardial delivered BM mononuclear cells (BMNCs) into the ischemic zone. In patients with acute MI, trials have utilized intracoronary delivery of BMNCs with considerable variability in the number of cells and the timing of delivery as well as the measurement of the primary endpoint.In patients with coronary heart failure (CHF) following MI, the goal is to promote myogenesis, utilizing skeletal myoblasts delivered into the previously infarcted zone.For peripheral arterial disease, studies are focusing on claudication and critical limb ischemia (CLI).

Possible routes for cell therapy to the heartStrauer BE, Kornowski R. Circulation 2003;107:929-34.

CFXIn red at the bottom of the heart on the image is a representative apical lesion of the left ventricle by MI.The balloon catheter is localized in the infarct-related artery and is situated above the border zone of the infarction. The possible route of cell infusion and migration into the infarct are represented by the blue and green arrows. The 2 small figures at bottom right and left depict the transendocardial and intramyocardial route of cell therapy.Possible routes for cell therapy to the heart

Werner N et al. N Engl J Med. 2005;353:999-1007.N = 519 males with CAD, mean age 66 yEPC number has prognostic importance1.000.980.960.940.920.900100200300365Group 3 (high EPC level)Group 2 (medium EPC level)Group 1 (low EPC level)0DaysEvent-freesurvival

Open label non-randomised trial

Largest trial (391 pts) comparing BMNCs vs conventional therapy in patients with heart failure due to healed infarction. Simple method of delivery. Largest (60 moths) follow-up. Comprehensive assessment

BMNCs safely produced a sustained benefit on clinical outcome and LV performance not observed before

This STAR sheds light on the mechanisms of LV benefit of cell therapy

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