CURRENT ADVANCES IN HEART TRANSPLANT

by Mirajini Manoharan

CONTENT
Introduction Mechanically Assisted Devices

What is it? How does it work? Who is it used for? Limitations

Stem Cells

Extra cellular Matrix Decellularization Recellularization

INTRODUCTION
Heart transplants: An allograft is the only definitive treatment for endstage heart failure But:

Shortage of organs Currently, fewer than 3000 donor hearts per year are available worldwide vs. An estimated 12 million new annual diagnoses of heart failure

MECHANICALLY ASSISTED DEVICES

WHAT IS IT?
o

o o o

Not an Artificial Heart Assist the ventricles in pumping blood to successfully restore the patients blood flow Reduce the work load of the ventricles Relieve symptoms of heart failure 2 types: o Left ventricular assisted device (LVAD) o Right ventricular assisted device (RVAD)

HOW DOES IT WORK?

WHAT IS IT USED FOR?

1. 2.

3.

Bridge to transplant Bridge to recovery Destination therapy

LIMITATIONS
Infection Thrombus formation Mechanical breakdown Right sided heart failure

STEM CELLS

STEM CELLS
Cell therapy Whole organ engineering

WHOLE ORGAN ENGINEERING

Extracellular Matrix Decellularization Recellularization

EXTRACELLULAR MATRIX (ECM)

Consist of protein that are secreted by the cells These ECM proteins are site specific Guides organ development, repair and physiologic regeneration

In cell engineering these proteins provide footprint of the previous resident cells .

DECELLULARIZATION

RECELLULARIZATION

SUMMARY
Introduction Mechanically Assisted Devices

What is it? How does it work? Who is it used for? Limitations

Stem Cells

Extra cellular Matrix Decellularisation Recellularisation

QUESTIONS?

REFERENCES

Kirklin J.K., Naftel D.C., Kormos R.L., Stevenson L.W., Pagani F.D., Miller M.A. et al. The Fourth INTERMACS Annual Report: 4000 implants and counting. The journal of Heart and Lung Transplantation 2012 Feb; 31: 117-126 Rose E.A., Geljins A.c., Moskowitz A.J., Heitjan D.F., Stevenson L.W., Dembitsky W. et al. Long- Term use of Left Ventricular Assist Device for end- stage heart failure. N Engl J Med 2001; 345: 14351443 Maddox T.M., Heart Disease and Left Ventricular Assist Device (LVAD) [internet]. 2012[updated 2012 Feb 22; cited 2012 Mar 20] available from: http://www.nhlbi.nih.gov/health/healthtopics/topics/vad/ What is a Ventricular Assist Device [internet] 2012 [ updated 2009 Sep; cited 2012 March 20] available from: http://www.webmd.com/heart-disease/treating-left-ventriculardevice

REFERENCES (2)

New York Presbyterian. Artificial Heart- Ventricular Assist Devices (VADs) [internet] 2012 [cited 2012 Mar 20] available from: http://nyp.org/services/ctsurg/vads.html Crapo M. P., Gilbert W. T., Badylak F. S.. An overview of tissue and whole organ decellularization processes. Biomaterials - 2011; 32: 3233- 3243 Stubbs L.S, Crook J.M., Wayne A.M., FRACSa.b, Newcomb A.E., FRACSb.c. Toward Clinical Application of Stem Cells for Cardiac Regeneration. Heart, Lung and Circulation 2011; 20:173-179 Ott H.C., Matthiesen T.S., Goh S., Black L.D., Kren S.M., Netoff T.I., Taylor D.A..Perfusion-decellularized matrix: using natures platform to engineer a bioartificial heart.Nature Medicine 2008 Feb; 14: 213- 221 Iyer R.K., Chiu L. LY., Reis L.A., Radisic M.. Engineered cardiac tissues. Current Opinion in Biotechnology 2011; 22: 706- 714

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Makkar R.M., Smith R.R., Cheng K., Malliaras K., Thomson L.E.J., Berman D., Czer L.S.C., Marbn L., Mendizabal A., Johnston P.V., Russell S.D., Schuleri K.H., Lardo A.L., Gerstenblith G., Marbn E.. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 2012; 379- 895- 904 Taylor D.A.. From stem cells and cadaveric matrix to engineered organs. Current Opinion in Biotechnology 2009; 20: 598- 605 Song J.J., Ott H.C.. Organ engineering based on decellularized matrix scaffolds. Trends in Molecular Medicine 2011 Aug; 17: 424- 432 Ilic D., Polak J., Stem cell based therapy where are we going. Lancet 2012 Mar; 379; 877- 878