The longitudinal monitoring for the myocardium

The imaging techniques , in suitable parameters , provide the connection between the cell therapies and the clinical procedure . The longitudinal monitoring provides information about the functioning mechanism of the reprogrammed cells in the in vivo environment . The review presents the imaging techniques that are able to explain the cause for the limited restoration process of the cell therapies in the cardiac tissue .

The human body contains approximately 3 , 7 × 10¹³ cells . The heart contains 6 × 10⁹ cells , in 300 grams ( figure 1 ) . The damage of the heart does not lead automatically to the regeneration of the full functional capacity . The scar formation and the inflammatory signals may not be enough to have a full regeneration of the cardiac tissue . The regenerative medicine enhances the healing mechanisms of the body with the cell therapy .

Figure 1 . The number of cells in the parts of the human body .
Copyright ( 2014 ) Katie Vicari / Nature Publishing Group

The minimum number of injected cells that is detectable by the imaging techniques is in the range of 10⁴ - 10⁶ cells . The heart contains 2 × 10⁷ cells in one gram of tissue , in the left ventricle . The fused positron emission tomography ( PET ) - computed tomography ( CT ) image of the porcine heart is an example for the technique ( figure 2 ) . The long arrows point to the trajectory of the thoracotomy . T is the inserted tube . The short arrows point to the 10⁸ human mesenchymal stem cells , injected in the left ventricle ( LV ) . The %ID / g is the percentage of the uptake by the injected human cells in one gram of porcine cardiac tissue .

Figure 2 . The PET - CT imaging of the expression for the reporter gene in the porcine myocardium .
Copyright ( 2009 ) RSNA

The results of a porcine model for the myocardial infarction identifies as the time for the maximum proliferation at an interval of 33 - 35 days after the injection of the mesenchymal stem cells in the myocardium .

The injected cells are not tracked in vivo if they are not labelled in vitro . The nanoparticles , as the exogeneous label , provide a strong contrast in a short acquisition time , but it is unreliable in the long - term monitoring . The incorporation process of reporter genes labels indirectly the target cell . The reporter gene in the nucleus creates reporter proteins secreted in the cytoplasm . The imaging technique detects the reporter proteins . The ideal cell label stays inside the target cells for a long time , is non - toxic , is in a concentration that is stoichiometric related to the number of target cells , and clears the system rapidly after the apoptosis of the target cells .

The challenges of the imaging techniques are the label dilution , and the cell tracking . The label dilution should remain inside the tracked cells until the apoptosis , but sometimes the dilution transfers to the host cells . The long - term tracking of the implanted cells through the imaging techniques has the challenge to quantify the number of cells from the initial implantation procedure that are alive , and the number of cells that proliferate , in the spatial and the temporal dimension .

The infarcted myocardium is trully regenerated with the aid from the cell therapies when the viable cardiac tissue in the infarct area has the volume increased , the fiber architecture is integer in structure , and the regenerated myocardium has synchronous contraction with the host .

References :

Naumova A . V . , Modo M . , Moore A . , Murry C . E . , Frank J . A . ( 2014 ) “ Clinical imaging in regenerative medicine ” , Nature Biotechnology , 32 ( 8 ) , 804 - 818 .

Willmann J . K . , Paulmurugan R . , Rodriguez - Porcel M . , Stein W . , Brinton T . J . , Connolly A . J . , Nielsen C . H . , Lutz A . M . , Lyons J . , Ikeno F . , Suzuki Y . , Rosenberg J . , Chen I . Y . , Wu J . C . , Yeung A . C . , Yock P . , Robbins R . C . , Gambhir S . S . ( 2009 ) “ Imaging gene expression in human mesenchymal stem cells : from small to large animals ” , Radiology - Radiological Society of North America , 252 ( 1 ) , 117 - 127 .

The effects on the heart after the replacement for the mitral valve

The echocardiographic investigation of the mitral valve shows which leaflet is degenerated , if the leaflet , and the ring , maintained the integrity , the state of the attachment for the chorda tendinae , the structure of the papillary muscles . Two follow - up studies present the outcome of the mitral valvuloplasty for the elderly patients .

A study presents the clinical findings for a man of 74 years old . He did not have regurgitation of the tricuspid valve before he had a prosthetic replacement for the mitral valve . The left side of the heart stabilised with the surgery . The aortic valve had an unaffected functioning mechanism . The postoperative atrial fibrillation progressed. The postoperative regurgitation of the tricuspid valve made an impact on the right side of the heart .

The rheumatic heart disease ( RHD ) , and the dilated cardiomyopathy ( DCM ) are the causes for the stenosis ( MS ) , and for the regurgitation ( MR ) of the mitral valve ( figure 1 ) . The effects of the increased pressure in the left atrium are the increased size of the left atrium , the atrial fibrillation , and the pulmonary hypertension . The atrial fibrillation produces the dilation for the ring of the tricuspid valve . The pulmonary hypertension generates the dilation of the right ventricle ( RV ) . The regurgitation of the tricuspid valve ( TV ) worsens the tethering of the tricuspid valve , and the dilation of the right ventricle .

Figure 1 . The regurgitation of the tricuspid valve after the mitral valvuloplasty . Copyright ( 2009 ) Journal of The American College of Cardiology .

Another follow - up study analyses the clinical outcome for 242 patients who had valvuloplasty for the repair of the mitral valve . The patients are free from the non - trivial regurgitation of the mitral valve in 94 . 3 ± 1 . 6 % after one month , 58 . 6 ± 4 . 9 % after five years , and 27 . 2 ± 8 . 6 % after seven years ( figure 2 ) . The freedom from the severe regurgitation of the mitral valve is 98 . 3 ± 0 . 9 % after one month , 82 . 8 ± 3 . 8 % after five years , and 71 . 1 ± 7 . 4 % after seven years .

Figure 2 . The non - trivial regurgitation of the mitral valve . Copyright ( 2003 ) Circulation .

The dysfunction of the mitral valve is generated by the rheumatic heart disease , by the ischemic heart disease , and by the bacterial endocarditis . The succes of the replacement for the mitral valve is assessed both in the short term , and in the long term effects on the quality of life for the patient .

References :

Flameng W . , Herijgers P . , Bogaers K . ( 2003 ) “ The clinical anatomy and pathology of the human arterial valves : implications for repair or replacement ” , Circulation , 107 , 1609 - 1613 .

Shiran A . , Sagie A . ( 2009 ) “ Tricuspid regurgitation in mitral valve disease : incidence , prognostic implications , mechanism , and management ” , Journal of The American College of Cardiology , 53 ( 5 ) , 401 - 408 .