Autogenous mesenchymal stem cells (MSCs): mode of action
This has been a raging debate in human medicine with a lot of papers published in recent years. Essentially the crux being whether MSCs provide their beneficial effects through release of locally-acting (paracrine) cytokines or through their incorporation into tissues as progenitor cells.
It seems to me, as a non-academic, that this debate is moving towards some kind of maturity as summarised in recent articles:
Mesenchymal Stem Cells: The Moniker Fits the Science
Boregowda, Siddaraju V.; Booker, Cori N.; Phinney, Donald G..
Stem Cells. Jan 2018, Vol. 36 Issue 1, p7, 4 p
https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.2713
The immunomodulatory function of mesenchymal stem cells: mode of action and pathways
Uccelli, Antonio; Rosbo, Nicole Kerlero.
Annals of the New York Academy of Sciences. Sept, 2015, Vol. 1351 Issue 1, p114, 13 p
https://nyaspubs.onlinelibrary.wiley.com/doi/full/10.1111/nyas.12815
The paracrine role of MSCs in a wide variety of tissues from skin to liver seems to be beyond doubt. Interestingly they appear to be sensitive to their microenvironment and have the potential to confer beneficial pro- and anti-inflammatory effects at the same time in some scenarios! Immunomodulatory is probably the best term.
Their potential as progenitor cells is more controversial. There seems to be quite good evidence to support the contention that this happens in bone, cartilage and adipose. In other tissues research has not fully demonsrated such a role.
For liver, the main current area of interest for us, the human state of affairs was reviewed in 2016:
Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases
Chien-WeiLee12Yu-FanChen23Hao-HsiangWu24Oscar K.Lee
Gastroenterology Volume 154, Issue 1, January 2018, Pages 46-56
https://www.sciencedirect.com/science/article/pii/S0016508517362807
To summarise in a few bullet points these authors state that:
‘MSCs …. trans-differentiate in vitro and MSC-derived hepatocyte-like cells can substitute for injured hepatocytes to restore liver function’
‘MSCs can localize to damaged liver and eliminate liver fibrosis’
‘MSCs have immunosuppressive and anti-inflammatory effects and promote survival of resident hepatocytes’
Differentiation into hepatocyte-like cells in vitro has been described. The extent to which this occur in vitro is less well-documented.
