Inflammation and Parenchymal Regeneration

00:01 Welcome.

00:02 We're going to continue the process of healing the injury.

00:06 And when all goes well, and according to plan, we will completely regenerate the parenchyma.

00:13 It's almost always doesn't happen perfectly, as we'll talk about.

00:18 But that would be the ideal circumstance.

00:21 So we'll cover this one first.

00:23 Here we are, in our roadmap, we've talked about moderating the mediators and acute inflammation initially.

00:31 We've talked about recruiting and activated macrophages.

00:34 And now we're going to try to regenerate parenchyma.

00:37 If we don't do that, we're gonna see the boxes on the bottom.

00:41 But right now we're going to try to regenerate parenchyma.

00:45 Every healing process is a combination of these two.

00:50 So just important that you keep this in mind, big picture.

00:53 Healing is somewhere on the spectrum between perfect regeneration and complete scarring.

00:59 And most healing is going to be some combination of the two.

01:04 Right now we're going to focus on regeneration.

01:07 Here's where we are in terms of our overlapping peaks of activity.

01:12 We've had some initial injury, at times zero.

01:14 We have the vascular response of edema.

01:17 We've had the acute neutrophilic infiltrate that peaked at about one to two days.

01:21 And we are at the peak of the macrophage recruitment, which is like three to five days.

01:28 And at that point, we are starting to do the regenerative process.

01:33 And this may take a long time, but it starts in the middle of the chronic inflammatory recruitment, right in the middle at that day three to five.

01:40 So that's the green arrow.

01:41 That's where we are for the next set of slides.

01:46 What's required to get regeneration? Well, three kind of important things have to happen.

01:51 We have to have limited damage, if we have extensive damage.

01:54 We lose our blueprint for putting that tissue back together.

01:58 So the damage has got to be somewhat circumscribed.

02:01 We have to have labile, or stable cells.

02:03 We haven't talked about this.

02:05 So labile cells are ones that are constantly in cell cycle all the time.

02:10 So marrow, and skin, and GI epithelium are constantly turning over.

02:14 So there are going to be cells that are going to be relatively easy to regenerate. Will just make more.

02:20 The stem cells are already cranking them out in profusion.

02:25 Stable cells are those that we can induce to proliferate with the appropriate signaling.

02:30 So hepatocytes, kidney epithelial tubules, endothelial cells, muscle cells, fibroblasts, there are a number, this is just a subset.

02:40 So you have labile or stable cells that's necessary.

02:43 in order to get regeneration. We have to make new cells.

02:46 And the matrix has to be preserved.

02:50 That's the blueprint.

02:51 It's the scaffolding upon which we're going to put the tissue back together.

02:55 So those three things have to happen if we're going to get perfect regeneration.