As we known,mesenchyal stem cell could secrete factors,such as IL-4 ,IL-10 ITF-Y,et,al.Did mesenchymal stem cell self-renew also have this phenomenon?
Yes. MSCs do secreted cytokines and express receptor to signal the activation of self-renewal, proliferation or lineage commitment. The balance between these cytokines in fact decide the MSC fate decision.
Hi Lui.
The first thing to say is that MSC are now termed "Mesenchymal Stromal Cells" rather than "Stem" cells. It is now recognised that these cells are not stem cells and are not capable of indefinite growth in culture. Indeed they probably originate in the body from several cell precursors (such as pericytes). How far these cells will divide in culture before they reach senescence depends on a lot of factors (high glucose in the media, for example, will hasten the onset of cellular senescence). Very generally though the cells will reach around cPD (cumulative population doubling) 25-30 before they stop dividing in culture (it is also dependent on the MSC donor and source i.e. adipose, bone marrow etc. of the MSC).
MSC secrete a number of factors in a constitutive manner - including IL-6, IL-8 and VEGF. There are LOTS of papers on this. Although they have a basal expression of a lot of proteins, in general, protein secretion is up-regulated in the presence of inflammatory cytokines (such as TNFa and IFNg).
In the presence of these inflammatory proteins MSC up-regulate a lot of other proteins as well as molecules that suppress the immune response (such as IDO-1 & PGE2).
Expression of TSG6 (involved in anti-inflammatory response) and SDF1 (involved in migration) are also up-regulated.
I am not aware of any "stem" factor being released. However growing the cells in low-glucose media and at a low density can help maintain the "stermness" of the population allowing them to expand more before they senesce. Older MSC populations that have entered senescence also secrete more proteins constitutively (i.e. without stimulation with TNFa etc). This is due to the cells acquiring a "Senescent Associate Secretory Phenotype" or SASP. I know as I have observed this in older populations of MSC.
Hope this helps (and if anyone does know of any secreted proteins that increase "stemness" I would be interested to know what they were!).
Gary
I should also say that growing the cells in hypoxia has also been reported to prolong their expansion.
Hi Lui,
I agree with all the points which Gary has mentioned. The main mechanism through which MSCs exert the therapeutic effect is through secretion of these paracrine factors. They secrete a wide range of factors which could play a role in angiogenesis, anti-inflammatory, anti- apoptotic etc., In addition, we have observed that these cells could also secrete factors such as LIF, GM-CSF, SDF-1, IGF-1 and PDGF which could play a role in supporting progenitor cell growth and promote proliferation.
As mentioned by Gary exposing these cells to hypoxic environment could enhance the secretion of angiogenic cytokines.
Indeed - some of these factors will undoubtedly act in a paracrine fashion (the cells express SDF1 and the receptor for this protein - CXCR4). And thus could enhance proliferation or migration etc.
MSC do not express Telomerase however (Zimmermann et al 2003, Leukemia), do not grow indefinitely in culture and most likely originate from a precursor cell(s) (pericytes) so I hesitate to use the term "stem" in describing these cells although they do have some "stem" like qualities such as tri-lineage differentiation - then again so do normal "fibroblasts" - see Blasi et al 2011, Vascular Cell.
The only thing that seems to distinguish MSC and fibroblasts (apart from lack of MHC class II molecules) is the Secretome of these cells. This has led many people (including myself) to come to the conclusion that they are a secretory form of fibroblast (see Haniffa et al 2009 : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635401/ )
Amable et al 2014, Stem Cell Research & Therapy give a good listing of some of the proteins MSC from various tissues secrete (in the supplementary table to this paper) but this is by no means comprehensive and their Secretome increases greatly after priming with inflammatory cytokines.
- Badges
- Science topic
- Similar topics
- Biological Science
- Immunology