The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (VIDEO Part 3)

In part 3, Professor Caplan discusses the science behind mesenchymal stem cells: sources of mesenchymal stem cells (MSCs), because all MSCs are pericytes one can find them in any tissue that has blood vessels, pericytes express markers of MSCs, frequency of pericytes in human tissue, most abundant source of pericytes is adipose (fat) tissue, adipose-derived stem cells, how MSCs are separated from fat, chemistries MSCs from different tissues are not the same, MSCs function at sites of injury, mesenchymal stem cell homing in mice, MSCs don’t make fat, they don’t make muscle. They come back as pericytes, and not all pericytes are MSCs.

Why does fat (adipose) stem cell therapy take more than one week?

Intravenously administered adipose-derived stem cells will tend to migrate back to the fresh wound site if it is not given an adequate time to heal. Therefore, it is essential to allow about one week after the mini-liposuction before administering any stem cells intravenously. Otherwise, there is a likelihood that the treatment will not be as effective. Additionally, it takes 5 five days to thoroughly test the adipose cell samples for aerobic and anaerobic bacteria as well as endotoxins.

In order to ensure that no patient receives an infected sample, at least 5 days must transpire before the cells can be confirmed safe and injected back into the patient.

Lastly, this 5-day waiting period enables our scientists to culture a small sample of each patient’s stem cells in the lab to observe how they are likely to proliferate once they are inside the body. If a patient’s cells show low viability, Stem Cell Institute doctors will supplement the treatment with additional cord-derived cells to compensate. The same can be done in cases of low cell yield.

Fat Stem Cells are not affected by weight or age

Mojallal et al. Aesthetic Plast Surg.
Fat represents a potent source of autologous stem cells. Historically, the majority of research using autologous stem cells involved stem cells collected from the bone marrow. This source is associated with a painful extraction procedure and relatively low concentrations of mesenchymal stem cells. In contract, mini-liposuctions represent a less invasive extraction approach. Additionally, adipose tissue has been shown to contain substantially higher number of mesenchymal stem cells as well as hematopoietic stem cells and endothelial progenitor cells.
The use of fat derived stem cells has grown exponentially in recent years for numerous indications. Perhaps the largest data set for fat derived stem cells is possessed by Dr. Bob Harman from Vet Stem, who has treated a total of more than 10,000 large animals with this procedure. The Cellmedicine clinic has had an excellent track record of success using autologous fat for treatment of multiple sclerosis having treated more than 200 patients.
One of the major limiting factors of stem cell therapy using your own stem cells (autologous) is that the potency and number of stem cells is believed to decrease with age and disease. These studies, however, have been performed primarily from bone marrow sources of stem cells. Any hematologist will tell you that with age the bone marrow becomes drier and possesses less cells. Studies have shown that bone marrow stem cells from patients with diabetes or from obese patients have less activity as compared to age matched controls. There has been some thought that the stem cells in the adipose tissue are protected from age and disease. A current study (Mojallal et al. Influence of Age and Body Mass Index on the Yield and Proliferation Capacity of Adipose-Derived Stem Cells. Aesthetic Plast Surg. 2011 May 26) from the Service de Chirurgie Plastique, Reconstructrice et Esthétique in Lyon France sought to address this. The investigators assessed 42 women who were divided into two groups: age ≤ 40 or >40 and BMI ≤ 25 or >25. Fat tissue was harvested via manual lipoaspiration from the abdominal region. After centrifugation, 100 ml of lipoaspirate was sent to the laboratory for isolation and cultivation of ASCs. The investigators found that average cell yield was 0.380 × 10(6)/ml. Cell yield and proliferation capacity did not show statistically significant correlation to the age and BMI of patients, nor was there a statistically significant difference between cell yield and proliferation capacity between the different groups.
The study looked at some very basic parameters: cell number, viability and proliferative ability. It may be that adipose stem cells may exhibit differences in immune modulatory potential or differentiation potential between donors. This was not assessed. Additionally, the adipose derived cells were not assessed between donors suffering from different conditions. Despite these shortcomings, the data appears to support the hypothesis that adipose derived stem cells may have some advantages as compared to bone marrow stem cells, at least for autologous uses.

Fat Stem Cells Turn to Muscle: A Treatment for Muscular Dystrophy?

New research published in the journal Biomaterials by University of California, San Diego researcher Adam Engler suggests fat-derived stem cells that are developed on a stiff surface transform into mature muscle cells. This remarkable discovery could lead to new treatments for muscular dystrophy in the future.

Fat stem cells and bone marrow stem cells were grown on surfaces with different degrees of hardness ranging from very hard bone-like surfaces to very soft brain tissue-like surfaces.

The researchers found that the fat derived stem cells were much more likely (up to fifty times) to exhibit proteins that are essential to the cells becoming muscle tissue.
Yuk Suk Choi, a post-doc team member, says that the fat-derived stem cells seem to proliferate better than bone marrow cells when introduced to the hard surfaces. “They are actively feeling their environment soon, which allows them to interpret the signals from the interaction of cell and environment that guide development,” explained Choi.

Unlike bone marrow stem cells, stem cells from fat fused together to form myotubes. Although this phenomenon has been observed in the past, it has never been observed at such a high degree by Engler in the lab. Myotubes comprise an essential step in muscle formation.

Next, Engler and his team plan to observe how fused cells from fat perform in lab mice which are afflicted with a particular form of muscular dystrophy.

However, Dr. Engler cautioned, “From the perspective of translating this into a clinically viable therapy, we want to know what components of the environment provide the most important cues for these cells.”

Dallas doctor uses stem cell injections in cosmetic surgery

 

Dr. Jeffrey Caruth, a Texas OBGYN who is performs cosmetic
surgery has started using adult stem cells to increase the effectiveness of "fat
grafting".  The use of fat as a filler has been used in plastic surgery for
decades.  The only problem has been that as time passes, the fat gets resorbed
by the body.  A publication from Japan (Yoshimura et al. Cell-assisted
lipotransfer for facial lipoatrophy: efficacy of clinical use of adipose-derived
stem cells. Dermatol Surg. 2008 Sep;34(9):1178-85
) demonstrated that if fat
stem cells are mixed in with the fat, the rate of resorption is markedly
diminished.  Given that the cells administered are the same cells of the body,
the possibility of immunological reaction is absent. 

 Jackie Jones is the second patient in North Texas to
undergo this type of cosmetic surgery.  "I will be happy to see the lines on my
face go away," she said. "I will be happy with the new shape of my body and that
in itself is really exciting to me."

Dr. Caruth said stem cells help solve a problem that has
plagued prior procedures. "The problem has been with traditional fat grafting
that you put a volume of fat into the face, the buttocks and then in a month or
two or three there is significant volume loss due to death of the fat cells you
put in,"  he continued "You’re going to get twice the graft survival versus
other methods," Caruth said.

 It is known that conventional artificial filler injections
usually last up to a year and regular fat grafting lasts anywhere between three
to five years.  It is anticipated that addition of stem cells will allow the
grafts to maintain shape for up to 10 years.

 Dr. Jeffrey Kenkel, the vice chairman of plastic surgery
with UT Southwestern, stated "There is a tremendous amount of excitement about
stem cells," he said. "We just don’t have a lot of information about them, about
how they work and how we control them to do what we want them to do."

 After the procedure Jones commented "I can really tell a
difference. The lines between my eyebrows are gone."

Human fat contains not only stem cells but other cells such
as T regulatory cells that control inflammation.  Given that inflammation is
associated with aging, there may be several mechanisms at play responsible for
the effects seen by addition of fat stem cells to fat grafts.  An example of fat
stem cells exerting therapeutic effects can be seen in multiple sclerosis as
reported in this publication

http://www.translational-medicine.com/content/pdf/1479-5876-7-29.pdf