Every year (for students like myself at least), April, May & June represent times of the year where everyone is basically really dull – no one eats properly, we lock ourselves to our seats for countless of hours, and we’re too guilty to go out and have a nice meal or even do anything else besides clogging our brains with information prior to our examinations.
I’m not sure if I’ve mentioned this before (who am I kidding, I most probably have), I am in love with stem cells and regenerative medicine. Though it doesn’t stop me from dreading my two hour written examination.
On the bright side, everything that I have learnt on bone regeneration, wound healing, skeletal muscle regeneration, and retinal stem cells, has been really mind-stimulating. The more I know, the more there is to know! There is an obvious need for any one person to read between these different fields and connect the dots. Across different tissues, there is noticibly similar patterns of regeneration. If someone would just have the time to go through everything and string them together.
In my opinion, the most notably similarity across regenerative tissues are a set of cells that help the main constituent cells in an organ to carry out the process of recovery. I call these helpful cells, “Assistive Stem Cells” (ASCs). These ASCs are likely to be different types of cells in different tissues, but they would all carry the similar role of providing growth factors, an optimum environment and any other necessary nutrients, as well as contribute to the specific cell tissue to replace the cell lost.
These ASCs are usually in a quiescent state (like most adult stem cells), and when there is an injury, they can be activated to proliferate, differentiate and produce more of the the tissue type. An example of ASCs are pericytes. Pericytes can be found within the endothelial vascular (blood vessel) network of the skeletal muscle and they naturally give rise to more skeletal muscle during an injury and carry out normal muscle regenerative processes. These pericytes are also termed mesoangioblasts in some papers.
Mesenchymal stem/stromal cells (MSCs) within the bone marrow of the skeleton (BM) has also been termed pericytes by some papers – this had led to many confusions.
MSCs from the BM naturally regenerate bone when there is a fracture. These MSCs/pericytes are also derived from the vascular network but in this case, the pericytes reside within the vessel network found in the skeleton instead of the muscle. When compared, both pericytes obtained from blood vessels of different tissue have similar molecular markers and in fact similar morphology.
- Reminder: These “pericytes” naturally give rise to different cell types because of their original residence within the specific tissue type. You’d think that if the cells came from the vessels, have similar markers and morphology, they could perhaps be interchanged between tissues and produce more tissue type for each other. This is not the case. In order to induce pericytes from the muscle to make skeleton, an exogenous expression of RUNX2 (mature skeleton gene) is required (Bianco P. & Robey, P.G., 2015). This means that muscle-pericytes do not naturally produce skeleton and vice versa.
Let’s try linking the knowledge that we have on salamander limb regeneration to ASCs. We know that salamanders (newts & axolotls) have natural limb regenerative capacities. During limb regeneration in salamanders, a group of cells of similar morphology (known as the blastema) forms post-amputation of the limb. This is the first step during limb regeneration, and these blastema cells are known to retain positional memory. This means, the cell that was initially giving rise to the skeletal muscle would dedifferentiate into a blastema cell type (more premature cell type), and redifferentiate (to a mature cell type) to give rise to more skeletal muscle as proven by lineage tracing (Simon A. & Tanaka, E. M., 2013).
Would it be incorrect to state that perhaps these ASCs residing within the same endothelial position in different tissues also possess positional memory – allowing ASCs to naturally give rise to more of the tissue type it is residing in, but refusing to give rise to other tissue types (despite the same morphological cell type found in that tissue)?
Perhaps we’re not so different from Salamanders after all.
1. BIANCO, P. & ROBEY, P. G. 2015. Skeletal stem cells. Development, 142, 1023-1027. doi:10.1242/dev.102210 (http://dev.biologists.org/content/142/6/1023.abstract)
2. SIMON, A. & TANAKA, E. M. 2013. Limb regeneration. Wiley Interdisciplinary Reviews: Developmental Biology, 2, 291-300. (http://onlinelibrary.wiley.com/doi/10.1002/wdev.73/abstract)