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  1. Jul 2018
    1. On 2014 Apr 07, Madhusudana Girija Sanal commented:

      Is there any evidence that decellularized scaffolds are the way to go for a heart! The heart is a syncytium (syncytium is a multinucleate cell which can result from multiple cell fusions of uninuclear cells) and the entire heart should work as a single huge coordinated muscle mass. If millions of cells are not connected to each other in the intricate way life threatening arrhythmia will kill the patient. This cannot be achieved in this model which is described here. Currently there is no convincing evidence in this direction. It is extremely difficult to repopulate the scaffold with live differentiated cardiomyocytes (or even undifferentiated cells) to make anything closer to useful. It is even more difficult to achieve proper blood supply to the repopulated cells in the scaffold to keep the cells alive even for few hours. Moreover, the scaffold proteins of the donor heart can cause graft rejection, even if is derived from 'induced pluripotent stem cells(iPSC)' derived 'patient's own somatic cells' are used to repopulate the scaffold. Totally artificial mechanical pumps (like "Abiocor" or even better ventricular assist devices [VA])) may be closer to reality and justify spending of public money than repopulated scaffolds. Repopulation of scaffolds may work for simple organs such as a urinary bladder (because bladder for example is: (a) relatively simple organ in structure (b) not a vital organ IE; one will not die if one's bladder fails!). We have miles to go before we make a true 'lab made cellular-heart' mainly because of many unresolved fundamental and technological issues. The State and private investment in basic sciences like mathematics, physics, chemistry and fundamental biology is vital to achieve this kind of dreams (compared to investment in the direction of premature 'translation'). Investors and the society need to realize the importance of patience and watchful expectancy when it comes to investment in basic sciences for obvious reasons.


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  2. Feb 2018
    1. On 2014 Apr 07, Madhusudana Girija Sanal commented:

      Is there any evidence that decellularized scaffolds are the way to go for a heart! The heart is a syncytium (syncytium is a multinucleate cell which can result from multiple cell fusions of uninuclear cells) and the entire heart should work as a single huge coordinated muscle mass. If millions of cells are not connected to each other in the intricate way life threatening arrhythmia will kill the patient. This cannot be achieved in this model which is described here. Currently there is no convincing evidence in this direction. It is extremely difficult to repopulate the scaffold with live differentiated cardiomyocytes (or even undifferentiated cells) to make anything closer to useful. It is even more difficult to achieve proper blood supply to the repopulated cells in the scaffold to keep the cells alive even for few hours. Moreover, the scaffold proteins of the donor heart can cause graft rejection, even if is derived from 'induced pluripotent stem cells(iPSC)' derived 'patient's own somatic cells' are used to repopulate the scaffold. Totally artificial mechanical pumps (like "Abiocor" or even better ventricular assist devices [VA])) may be closer to reality and justify spending of public money than repopulated scaffolds. Repopulation of scaffolds may work for simple organs such as a urinary bladder (because bladder for example is: (a) relatively simple organ in structure (b) not a vital organ IE; one will not die if one's bladder fails!). We have miles to go before we make a true 'lab made cellular-heart' mainly because of many unresolved fundamental and technological issues. The State and private investment in basic sciences like mathematics, physics, chemistry and fundamental biology is vital to achieve this kind of dreams (compared to investment in the direction of premature 'translation'). Investors and the society need to realize the importance of patience and watchful expectancy when it comes to investment in basic sciences for obvious reasons.


      This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.