As a pioneer in the orthopedic use of autologous stem cells, I’m often asked to shed light on the increasingly confusing information out there, and to that end have put together a “Stem Cell Therapy Review Journal “.
One of the most common questions asked by asked by patients and doctors alike is why our stem cell lab doesn’t consider using adipose derived stem cells as the primary source of MSC’s for orthopedic purposes. After all, it would seem far easier to just take a little fat aspiration in a mini-liposuction procedure rather than performing a bone marrow aspiration (where we derive cells for orthopedic use). The problem is that source of adult stem cells is very important to their function.
Stem cells come in many shapes, sizes, and types. Some are more differentiated than others, while some are less differentiated. Take for example adipose derived mesenchymal stem cells (MSC’s). When these adult stem cells (MSC’s) are compared to bone marrow derived MSC’s for orthopedic uses such as bone or cartilage repair, bone marrow derived MSC’s beat the pants off fat derived stem cells (Vidal et al, Niemeyer et al, Jakobsen et al). The reason is that many adult stem cell types are already pre-differentiated down a certain lineage (in this case bone marrow MSC’s are more differentiated down orthopedic lineages such as cartilage and bone). Fat derived MSC’s are good at becoming more fat, or assisting the repair of wounds to the dermis or subcutaneous tissues. As a result, adipose derived MSC’s are great for cosmetic uses, modulating the inflammatory response, and assisting in the repair of acute nerve injury. Is it possible to select MSC’s out of adipose tissue that might be better for orthopedic applications? It may be, as a recent paper by Jiang discusses. However, you likely still have a fish out of water.
This same rule holds true for many other tissues. As an example, synovium derived MSC’s are about 20% better for orthopedic uses than bone marrow derived MSC’s. This is because, they are simply closer to the area in need of repair (in this case joint cartilage). And so it goes, cardiac muscle derived progenitors are a little better at cardiac muscle repair, etc… The closer the stem cells are to the target tissue in need of repair and the closer their function in the body is to the repair process for that tissue, the better.
One practical caveat to the source rule may be yield. Yield is how many cells you can get from an area for therapy. As an example, while periosteum stem cells from baby teeth may be very potent, you’re not going to isolate many stem cells from such a diminutive source. As a concrete example, synovial fluid can yield MSC’s for cartilage repair, but the numbers isolated directly from the fluid are usually well below the number needed to repair cartilage (or the cartilage would just repair itself). The same generally holds true for many other cell types derived from the tissues they serve. One way around this issue is culture expansion, or growing cells in culture to bigger numbers. This is how the body handles replacement of stem cells when they are used for daily repair and maintenance; it simply makes more cells. This process can amplify stem cells about 100-1,000 times more than the number harvested.
Here’s a summary of some common stem cell sources (and a few not so common) that seem to be helpful in certain conditions:
- Adipose derived stromal vascular fraction- These are cells that can be obtained by performing an aspiration of fat during liposuction. This adipose tissue is then processed in a simple lab or using a commercially available machine. About 1 in 100 of these cells is a mesenchymal stem cell, so it’s a dilute concentration of stem cells rather than isolated stem cells. These cells appear to be helpful for cosmetic, neural, and anti-inflammatory properties.
- Bone marrow derived cells: These cells can be concentrated in a commercially available centrifuge or by a lab to produce a bone marrow aspirate concentrate (BMAC) or isolated and grown in a more sophisticated lab to bigger numbers. They are appropriate for many uses including cardiac, pancreas, and orthopedic uses (as well as others).
- Cardiac muscle derived progenitors: These are either progenitor cells (stem cells that are more differentiated) or mesenchymal stem cells that are obtained by cardiac muscle biopsy. Since they are cardiac specific, they would be appropriate for cardiac use.
- Synovial derived mesenchymal stem cells- These are orthopedic MSC’s that are specific for cartilage repair and are derived from either a synovial tissue biopsy or a synovial fluid draw.
It’s important to note that almost any tissue can yield stem cells or progenitors. As an example, MSC’s have been obtained from periosteum, cardiac muscle, fat, dermis, blood vessel walls, and marrow, just to name a few. You can even get stem cells from the endometrial tissue obtained from menstrating women. In summary, the closer the stem cell is to its original location or function in the body, the better the stem cell is at repairing that specific area. So in stem cells, source matters.