Mesenchymal stromal/stem cells or MSCs are widely used by unproven clinics, but MSC research also suggests real promise in specific areas. Clinics mainly use adipose MSCs (often called SVF) or bone marrow MSCs. However, umbilical cord MSC preparations are getting more popular too. Many questions swirl around the use of MSCs including what exactly are in these cellular preps and how many stem cells they contain. Some clinics tout both adipose and marrow MSCs or even mix the two. Other clinics focus primarily on just one or the other, and then criticize the type they aren’t using.
A new paper analyzing adipose and marrow MSCs addresses some of these questions and raises big concerns about clinic applications.
MSC analysis points to challenges
Comparative single-cell transcriptional and proteomic atlas of clinical-grade injectable mesenchymal source tissues, Science Advances. In this piece, the team found some very concerning attributes of common marrow and fat MSC preparations. From a news item on the work:
“Their atlas revealed that MSC concentrations in BMAC formulations were extremely low, and that overall, there were no comparable “stem cell” types in both therapies. In fact, the two treatments had very different compositions; BMAC was composed mainly of red and white blood cells, and ADSVF was composed mainly of connective tissue cells.”
In other words, marrow and adipose MSC preps often don’t have many stem cells in them. It may be important therapeutically to isolate the actual stem and precursor cells out of the cellular mixtures prior to use if you are invoking a stem cell-based mechanism. These types of MSC preps are also quite distinct from each other. You’ll also note in the figure panel above from the paper the MSCs are off in a tiny cluster (red box) in the bottom right all by themselves. In Fig. 2B, cultured MSCs are also shifted away from the primary MSCs. Go to the paper to see this. Other challenges include quantifying MSCs and their relative scarcity in tissue preps.
More recommended reads
Disruption of TGF-β signaling pathway is required to mediate effective killing of hepatocellular carcinoma by human iPSC-derived NK cells, Cell Stem Cell. This paper comes from a team led by the wonderful Dan Kaufman down at UCSD. Dan is also a member of The Niche Medical Advisory Board.
Scientists May Finally Know How to Turn White Fat Into Brown, Medscape. Here’s the source JCI paper: White adipocytes in subcutaneous fat depots require KLF15 for maintenance in preclinical models. Deletion of KlF15 produces a switch to beige fat, an intermediary.
U.K. publishes first guidelines for human embryo models grown from stem cells, Science. The subtitle is: “New code of practice aims to provide clarity about the ethical and legal boundaries of a rapidly developing research field.” Here’s the code: The SCBEM Code of Practice supports the development of best practice for the generation and use of human stem cell-based embryo models (SCBEMs) for research. This one will take some reading to get into the details. Some of the take-homes: “One of the group’s chief recommendations is to establish an oversight committee to review every research project that uses stem cell–based embryo models. Made up of scientists, legislators, sociologists, and bioethicists, the panel would consider the moral, social, and ethical implications of the research before deciding whether to give the go-ahead.” and “…researchers must justify the length of their experiments on a case-by-case basis, Sturmey says.”
Advancing Parkinson’s disease treatment: cell replacement therapy with neurons derived from pluripotent stem cells, Stem Cells. Review from Jeanne Loring and colleagues.