In Vivo Release of Activated Stem Cells Following Abdominal Lipolysis
Compared to
External Modalities for Stem Cell Release From Abdominal Tissue
May 2023 Essay by Walter P. Drake.
At Blue Marble University, we include the study of Stem Cell Biology, being the “new medicine” in all of our online bio-medical doctoral programs including:
Ph.D. Stem Cell Medicine:
https://panamacollegeofcellscience.org/summary/curriculum/
M.D. Degree online:
https://bluemarbleuniversitymedicalschool.com/january-2021-online-medical-curriculum-and-course-descriptions/
D.Sc. Biomedical Engineering:
https://bluemarbleuniversity.files.wordpress.com/2023/03/2023curriculumd.sc_.biomedicalengineering.pdf
Ph.D. Pharmaceutical Science:
https://bluemarbleuniversity.com/online-ph-d-in-pharmaceutical-science/
N.D. Alternative Medicine:
https://bluemarbleuniversity.files.wordpress.com/2023/01/ndcurriculumjanuary2023.pdf
The most widely adopted stem cell therapy protocol being used worldwide (except the U.S.) is known as the SVF protocol. This stands for “Stromal Vascular Fraction” which contains stem cells and a rich soup of cytokines isolated from abdominal fatty tissue following mini-liposuction. The procedure is presented in great detail in a recent article published on our medical school website entitled: “SVF- The Gold Standard for Stem Cell Therapy”
https://bluemarbleuniversitymedicalschool.com/2023/05/06/svf-the-gold-standard-for-stem-cell-therapy/
In brief, we remove 50 cc of fatty abdominal tissue via a mini-liposuction, use enzymes to break up the collagen holding everything together, and separate out the stem cells and soluble cytokines and growth factors. The process requires light activation at various wave lengths to “activate” the stem cells, which are then re-injected back into the same patient.
While this procedure is being used worldwide to cure and control almost all of our most debilitating diseases and conditions, it remains a relatively expensive outpatient surgical procedure.
It is well known that we all have inherent, yet dormant, stem cells residing throughout the body. With stem cell therapy, we extract some stem cells, activate them with a light box, and re-inject them back into the same patient.
What if we could stimulate and activate our own innate dormant stem cells and avoid liposuction altogether?
In January 2023, I postulated that “Since stem cells are resident in virtually every tissue and organ, the patient does not need any more stem cells. What the patient needs is the stimulation and activation of endogenous growth factors and cytokines that can come about from the in vivo stimulation by one or more means.” [1]
It was further suggested that: “Techniques, such as those use in fat reduction, should be explored as a means to dissociate the extracellular matrix of abdominal tissue in situ, with the goal of activating innate systemic stem cell activity. This may be achieved by in situ lipolysis, laser applications, ultrasound, and other modalities likely to dissociate and break down the adipose tissue extracellular matrix, thereby releasing various endogenous stem cell activating cells and factors into the periphery.”
This led to a Research Note entitled: “Drake-Hicks Protocol For In Situ Release of Mesenchymal Stem Cells and Cytokines Following Abdominal Lipolysis” [2] in which various injection lypolysis techniques were reviewed which might contribute to the release of stem cells in vivo, and hence bypass the current need for liposuction being part of the stem cell therapy protocol. This procedure was named “In Situ Abdominal Lypolysis” to emphasize that injections and external lipolysis applications such as laser lipolysis, ultra sound and an array of fat dissolving equipment are applied to the patient without the need for liposuction.
In this essay, we hope to stimulate thinking on the part of our students by discussing in more depth, the various available externally applied techniques for dissolving fat.
If you can dissolve abdominal fat efficiently, you are automatically releasing stem cells into the peripheral blood system for distribution throughout the body to achieve the same therapeutic effect that results from liposuction and SVF processing.
And since growth factors, cytokines, and other messenger molecules would also expected to be released via a break down of the adipose tissue cellular matrix, this surge of soluble factors might be expected to stimulate the co-released stem cells resulting in a similar therapeutic effect observed worldwide following SVF stem cell therapy. This surge in circulating soluble factors could possibly substitute for light box activation required in the SVF protocol.
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While the Drake-Hicks Protocol involves Injection Lypolysis, the question is are there any external modalities that may be likewise effective in dissolving fat and releasing stem cells into the periphery.
These are the four external modalities used for fat reduction that might be effective in causing stem cell release or stimulation in vivo:
LIPUS [Low Intensity Pulsed Ultrasound]
PEMF [Pulsed Electromagnetic Fields]
Ultrasonic Cavitation
LLLT [Low Level Laser Therapy]
(1) LIPUS [Low Intensity Pulsed Ultrasound]
A good starting point: Tan et al, “Low-intensity pulsed ultrasound stimulates proliferation of stem/ progenitor cells: what we need to know to translate basic science research into clinical applications”. Asian Journal of Andrology (2021) 23, 602–610 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577250/pdf/AJA-23-602.pdf
The authors state: “LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration; inhibition of inflammation and pain relief; and stimulation of cell proliferation and differentiation”, but most studies are in vitro.
However, with respect to bone repair, clinical studies show: LIPUS delivers low-intensity acoustic pressure waves that produce microbiomechanical interactions with the cells to elicit intracellular biological effects. This ultimately results in tissue repair and regeneration, a process named “mechanotransduction.” Accumulating evidence indicates that LIPUS is effective to stimulate osteoblasts, to promote bone formation, and to activate other stem/progenitor cells.
This paper demonstrated bone healing in patients with “non-unions”, with union occurring by 6 months: Chaudhry et al, Low intensity pulsed ultrasound (Lipus) as a non-surgical cost effective method of managing atrophic non-union, J Orthop Surg Rehabil. 2019;3(1):1-5.
However, there are many disagreements in the literature as to if LIPUS is effective at all for anything. Despite many in vitro studies, I could find nothing to support the idea that this procedure might be effective to stimulate stem cells in situ.
(2) Pulsed Electromagnetic Fields (PEMF)
In which a modulated electromagnetic field is generated
near the treatment site though an external coil
PEMF seems to have gotten a lot of attention, and an excellent review article is here: Cadossi et al, Pulsed Electromagnetic Field Stimulation of Bone Healing and Joint Preservation: Cellular Mechanisms of Skeletal Response: J Am Acad Orthop Surg Glob Res Rev. 2020 May; 4(5): e19.00155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434032/
PEMF has clearly been shown to stimulate bone healing. You are not going to have any “bone stimulation” without the participation of stem cells. So, we can deduce immediately that electromagnetic field pulsing goes deep into tissue and stimulates stem cells in the bone directly; as opposed to LLLT, which requires stimulating a “cascade of secondary effects that contribute to a range of local tissue and systemic effects”.
Some links to skin (primarily facial) applications: https://www.skintherapymaster.com/pulse-electro-magnetic-field-pemf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479364/ https://www.nualawoulfe.ie/blogs/latest-news/skin-rejuvenation-healing-and-collagen-synthesis
https://www.pemftherapyeducation.com/2017/11/pemf-therapy-gives-healthier-skin/
Conclusion: I am unimpressed with PEMF except for its use in pain management. It is, in the end, an electrical based modality, well suited to nerves and pain issues commonly involving electron transmissions within the human body. As a possible stimulator of stem cell activity, I do not see it, despite many in vitro studies which appear to have no correlation to positive clinical outcomes.
(3) Ultrasonic Cavitation for Fat Removal
Mentioned for completeness in reviewing possible modalities for fat dissolution, this procedure involves applying pressure on fat cells through ultrasonic vibrations. The pressure is high enough to make the fat cells break down into a liquid form. The body can then get rid of it as waste through your urine.
Ultrasonic cavitation tones the body using radio frequencies and low-frequency ultrasonic waves. These waves form bubbles around fat deposits under the skin. The bubbles then burst, breaking the fat deposits into the interstitial and the lymphatic systems where they are drained. The fat deposits are changed into glycerol and free fatty acids. Glycerol is then reused by the body while free fatty acids travel to the liver and are excreted as waste.
It appears to me that Damage is occurring, the main idea is to damage the fat cells. Will other cells be damaged—i.e. stem cells? Damage can be Good. In the process, will a positive result be obtained in that endothelial cells and endothelial growth factors will be released?
I like the idea of getting in there and stirring things up. This is what we are doing with liposuction and the processing of SVF.
In the end, I did not see enough to make me feel this modality was going to be better than our injection lipolysis approach, and as a method for fat reduction or body contouring, this method has been all but abandoned.
(4) LLLT [Low Level Laser Therapy]
There are many many papers discussing light in an in vitro setting. And for sure, this is like going down the rabbit hole finding this wavelength does this and that wavelength does that. This is to be totally avoided for our purposes. Shining lights on cell cultures may well alter differentiation, proliferation and so forth, but does not get us any closer to having good info for in situ stimulation.
A sample paper of the kind one can find relating to in vitro studies is the Wang et al paper relating to increased proliferation of MSC’s with Blue/Green wavelengths, and introducing the term “PhotoBioModulation”. Wang et al, “Red (660 nm) or near-infrared (810 nm) photobiomodulation stimulates, while blue (415 nm), green (540 nm) light inhibits proliferation in human adipose- derived stem cells”, https://www.nature.com/articles/s41598-017-07525-w
A good review for the positive effect of LLLT for facial rejuvenation is Avci et al, “Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring”, Semin Cutan Med Surg. 2013 March ; 32(1): 41–52 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126803/
This is a terrific paper that tries to give us a visual look at what is going on with LLLT, this first image describing tissue depth vs wavelength (click to make bigger):
And the second picture describing the in vivo effects of light stimulation of the skin (Click to make bigger):
Maybe the single best review of LLLT in a clinical setting is by Graeme Ewan Glass, who pulled together all the recent clinical uses of LLLT as of 2021: “Photobiomodulation: The Clinical Applications of Low-Level Light Therapy”, Aesthetic Surgery Journal, Volume 41, Issue 6, June 2021, Pages 723–738.
https://academic.oup.com/asj/article/41/6/723/6104785?login=true
He starts out with this refreshing note: “In the gray area between the commercial and therapeutic sectors, harnessing the clinical potential in reproducible and scientifically measurable ways remains challenging.” Then he goes on to a wonderful summary of the clinical use of LLLT for facial rejuvenation, specific skin conditions, and wound healing.
Erchonia is one maker of an LLLT machine for fat reduction, and their research has led to a published paper: Erchonia Historical Summary, from which we glean these important points:
Effectiveness at a depth of 6 cm!!!!: “… using an 8mW 635 nm wavelength line laser held above the skin at a distance of 6-8 inches. After 4-6 minutes of exposure, significant (80- 99%) release of fat from fat cells was documented to a depth of 6 cm”.
Even though actual laser penetration far less than 1 mm: “Lasers cannot penetrate the tissue more than a fraction of a millimeter, so there is no other primary responding tissue other than the outer part of the dermis. Still, such irradiation has secondary systemic effects.“
Secondary Systemic Effects: “secondary effects (secondary responses) which have been studied and measured in various contexts: increased cell metabolism and collagen synthesis in fibroblasts, increased action potential of nerve cells, stimulation of the formation of DNA and RNA in the cell nucleus, local effects on the immune system, increased formation of capillaries by the release of growth factors, increased activity of leukocytes, transformation of fibroblasts to myofibroblasts, and a great number of other measured effects. Therefore, “deep light penetration is not a necessity per se in biostimulation…The possible reason for this is that cells in the tissues subjected to the light produce substances that then spread and circulate in blood vessels and lymphatic systems.”
CONCLUSION
Clinical evidence for the effectiveness of all physical modalities varies from non-existent to disappointing, at least as far as in vivo stem cell activation is concerned. There has been too much emphasis on in vitro studies and way too much promoting that in vitro observations can achieve comparable clinical results.
I find LLLT to be the most persuasive physical modality in general, and the most likely source for some stem cell stimulation in vivo.
Do I believe that any of these modalities comes close to stem cell therapy with Stromal Vascular Fraction from the micro-liposuction of adipose tissue? No.
Do I believe that additional clinical studies will show that LLLT or any of the other modalities is equal to the benefits achieved for many diseases and most particularly for facial rejuvenation? No. What you have now is what it will be. Results will never be any better.
After review of these physical modalities used in fat loss, I conclude that none will be as effective as Injection Lipolysis described in the Drake-Hicks Protocol. In my opinion, what needs to be addressed is better enzyme formulations, lipolytic agents, and possibly laser based stem cell activators to better refine the protocol so that we can achieve something close to the therapeutic effects of SVF stem cell therapy…yet without the need for liposuction.
[1] Drake, Walter P, “Stem Cell Therapy Without the Stem Cells”, Panama College of Cell Science, Publisher, January 31, 2023
https://panamacollegeofcellscience.org/2023/02/01/stem-cell-therapy-without-the-stem-cells/
[2] Drake, WP and Hicks, LV Sr., “Drake-Hicks Protocol For In Situ Release of Mesenchymal Stem Cells and Cytokines Following Abdominal Lipolysis”, Panama College of Cell Science, Publisher, January 31, 2023.
https://panamacollegeofcellscience.org/2023/02/01/drake-hicks-protocol-for-in-situ-release-of-mesenchymal-stem-cells-and-cytokines-following-abdominal-lipolysis/
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