This post is kind of like a part 2 to my last PATH3304 post: Scaffolds for Biological Tissue Reconstruction. This lecture didn't have an outline, so guess I'll just have to wing it.
Repair capacity of the heart
Unfortunately, our hearts are not very good at fixing themselves up. That is because cardiac muscle cells generally don't divide. If cardiac muscle cells die, they tend to be replaced with scar tissue, and remaining cells hypertrophy. There are clusters of stem cells in the heart, but they are pretty rare. Therefore, prognosis for heart attack survivors isn't the best: their heart function often declines until it ultimately fails.
Cardiac tissue engineering
Like I said in my last post, cells, scaffold, and growth factors are collectively known as the "Tissue Engineering Triad," as they are all important factors in tissue engineering. Another important consideration is vascularisation: it's pretty much impossible to grow whole organs if not all of the cells will be able to get nutrients. Several different approaches have been trialled in cardiac tissue engineering: ring structures, cell sheets, decellularised scaffolds, and in vivo vascularised chambers.
Ring structures have been created with donor cardiomyocytes (such as rat cardiomyocytes- so far, we haven't found a willing human donor- wonder why? :P) on a collagen hydrogel. This approach is relatively simple, and allows for some modification of scaffold and cells. Since this technique doesn't take vascularisation into account, its size is limited. Furthermore, its contractile force is quite low. Ah well, back to the drawing board!
A second approach involves making cell sheets out of rat cardiomyocytes or iPS (induced pluripotent stem cells). Once again, this is a relatively simple approach, and doesn't need any kind of scaffold. Once again, however, contractile force is low, and lack of vascularisation means that size is limited.
A third approach involves a decellularised scaffold, which I mentioned here. It involves rat cardiomyocytes cultured on a decellularised donor heart. These tissues can be assembled fairly quickly, and are large 3D structures (as compared to the smaller 2D structures of the other approaches). An obvious limitation with this method is that you need donor tissue, and the procedure is quite complex. Furthermore, the contractile force is still quite low.
A fourth approach involves growing tissue in a special chamber in vivo. These chambers can have holes in them (which I think encourages the growth of blood vessels or something?). Advantages include the growth of large 3D structures, but unfortunately, the procedure is fairly complex and the contractile force of the resulting structure is still low.
Obtaining cardiomyocytes
As you may have noticed, a recurring theme with the approaches for cardiac tissue engineering is that donor cardiomyocytes are required. This is a massive problem, as it's not exactly reasonable to ask a healthy person to donate part of their heart. As such, other sources, such as adipose-derived stem cells, have been considered. Adipose stem cells are derived from first performing liposuction on a patient and then isolating the stem cells.
After the adipose stem cells (ASCs) have been obtained, the next challenge is to get them to differentiate into cardiac muscle. Trichostatin A was found to increase expression of cardiac actin, though this did not cause contraction. Co-culture of ASCs with rat cardiomyocytes, however, was more likely to induce differentiation of human cardiomyocytes.
iPS (induced pluripotent stem cells) have also been investigated. iPS cells can be derived from fibroblasts which have been specially treated in order to become pluripotent. In order to optimise differentiation, several techniques have been trialled, such as adding trichostatin A or co-culture, just like with ASCs. (I think. This might have been where I was zoning out. I blame it on the lecturer turning out the lights because I just felt sleepy for the entire second lecture. But maybe I was tired because it was that time in the afternoon when I get sleepy? I don't know.) One of the risks of using iPS cells is that there seems to be a risk of forming teratomas, which are tumours of multiple cell types.
Other stuff
The lecture finished here because it went overtime, but the lecturer said that the slides would go up and they would be "pretty self-explanatory," or something along those lines. Well, I'm looking at them now, and it seems like the main points are that MSCs (remember them?) have paracrine activity involved in angiogenesis, and thus may improve vascularisation. Also there's another slide that says that hypoxic ASCs may also stimulate angiogenesis. According to the summary slide, this may also be through paracrine mechanisms, or the ASCs themselves may differentiate into vascular wall cells.
And that's all of my posts down for the week!
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