Mesenchymal Stem Cells Rarely Engraft But Work in a “Hit and Run” Manner

Even though this paper was published in 2012, it is a very important study that deserves a wide reading and lots of discussion.

The paper is “Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation” from Kathleen Le Blanc’ s laboratory, which was published in Stem Cells 2012;30:1575–1578.

In this paper, Le Blanc and her colleagues examined autopsies from patients who had received mesenchymal stem cell transplants. Since many scientists consider mesenchymal stromal cells (MSCs) a novel treatment for a variety of medical conditions, it is crucial that the fate of MSCs after infusion is better understood. Also, the long-term safety profile of MSCs is also quite important. DO they cause malignant transformation and ectopic tissue formation? Autopsies are an excellent way to address this questions.

The Le Blanc laboratory examined autopsy material from 18 patients who had received MSC transplants from people other than themselves. They analyzed 108 tissue samples from 15 patients by means of polymerase chain reaction (PCR) to search for the DNA of MSCs from donors in the tissue. If such foreign DNA was present in the tissues of the stem cell recipients, this would indicate that the MSCs had engrafted into the tissues of the patient. Unfortunately, MSC donor DNA was detected in only one or several tissues including lungs, lymph nodes, and intestine in eight patients at very low levels (from 1/100 to <1/1,000). Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, which simply means that the more time had elapsed since the time of the MSc transplant, the less likely it was that MSC DNA was found in the patient. For example, MSC DNA was detected in nine of 13 patients whose MSC infusions had been given within 50 days before sampling, in only two of eight of those infusions that had been given earlier.

On a more positive note, there were no signs of ectopic tissue formation or malignant tumors of MSC-donor origin upon macroscopic or histological examination of the tissues of the autopsied individuals.

What does all this mean? MSCs appear to mediate their healing capacities through the molecules that they secrete. This is called a “paracrine” mechanism. and MSCs seem to engraft into host tissues only very rarely. Instead MSCs come to a damaged tissue and stimulate the endogenous healing mechanisms already present. After doing this job, MSCs do not typically stick around. Thus, MSCs seem to work in, what Le Blanc calls a “hit and run” mechanism.

Because MSCs do not seem to engraft over a long period of time, the potential adverse reactions to these cells seems to be largely limited. Thus these cells are quite safe, but their effects are almost certainly indirect to some extent.