Three-Dimensional Engineered Heart
Summary:
A new technique was developed that allows neonatal rat cardiac myocytes to form spontaneously and coherently beating 3- dimensional engineering heart tissue in vitro. This new culture system utilizes a 3-dimensional collagen matrix to form a spontaneously and coherently beating cardiac myocyte matrix that offers the following advantages:
1- A 3 dimensional structure rather then monolayers that better resemble an intact heart tissue
2- Dedifferentiation and overgrowth by non-cardiomyocytes was inherently inhibited
3- Gave the opportunity to determine contractile force in standard organ baths
4- Stable cultivation time and measurement of contractile force
5- Provide simple genetic manipulation in comparison with intact heart tissue
After 26 days of casting, the contractile activity was monitored in standard organ baths or continuously in a CO2 incubator for up to 18 days. Long-term measurement revealed an increase in force between 8-18 days after casting and stable forces thereafter. On the 10th day the twitch amplitude of electrically paced engineered heart tissue was 0.51 nN at length of maximal force development in addition to a maximally effective calcium concentration.
Overall the engineered heart tissue retained many physiological characteristics of rat cardiac tissue such as: A positive force-length and a negative force-frequency relation, high sensitivity to calcium etc. and allowed efficient gene transfer with subsequent force measurements.
For your interest here is a short video of the latest development of this topic:
http://www.cnn.com/video/#/video/health/2008/01/15/pkg.rat.heart.update.kare?iref=videosearch
Topic was chosen because:
The new cell culture model (3-Dimensional) provides a better physiological way to build a beating heart tissue then the monolayer culture model. In addition, it provides the opportunity to study the consequences of the genetic, mechanical and pharmacological manipulation in vitro under controlled condition. The rat cardiac myocytes were chosen because they are a standard model, well characterized and easy to prepare in large quantities. However, this indicates that engineered heart tissue of different shape could potentially be useful as tissue equivalents for in vivo tissue repairs. This could be a huge breakthrough in medicine as this will greatly increase the life expectancy of many individuals that suffer from heart diseases.
6 comments:
After the lecture on extracellular matrices, it's amazing how the ECM can direct cell differentiation. I know that this research is very new and still in development, but there is so much potential in this way of producing viable transplants for human beings. To think that one can take the tissue of a deceased individual and create a viable living organ from it boggles my mind. I would like to know what other tissues/organs in the body, that we know have established ECMs, will allow for this process of development? Any Ideas?
We talked in class that mechanical stress we normally experience in our body dictates some of the morphologies and normal functions of many of our organs. Therefore, I wonder if an in vitro synthesized heart would be reliable in the long term to be able to withstand the stress and strain that a real heart experiences if it is actually implanted in the case of a heart transplant.
The engineered heart tissue possessed similar physiological characteristics to rat cardiac tissue, but structurally and functionally, how does the tissue compare? Additionally, what is the interaction between the cardiac myocytes and the collagen matrix that contributes to the coherent beating?
I think it's astounding that the neonatal rat cardiac myocytes cano beat COHERENTLY in an in vitro 3-dimensional engineering heart tissue. I wonder if that's because a group of cells begin to function like our SA node and initiate the beating.
Will this be able to take neural signals in future application?
The 3D collagen matrix indeed helps to structure the engineered 3D heart, so does that mean we can model the engineered hearts into any shape we want if we culture the myocytes on different shapes of 3D collagen matrix Do you know how long can these engineered hearts live in the water bath? and do the cells of an engineered heart exhibit different cell morphology than those of a real heart?
This research sounds promising. Yet this has only been tested on rats. Will the size be an issue (hard to make or maintain function) when it comes to human beings?
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