Adipose-derived stem cell therapy

If you are reading this article you are likely looking for the answers to two questions. The first question is:

Will stem cell injections help me with my chronic pain?

The second question is:

What are the differences between adipose derived stem cells and bone marrow derived stem cells?

Lipoaspirate Prolotherapy or Adipose-derived stem cell therapy is a regenerative injection treatment that stimulates repair of osteoarthritic cartilage and bone through the use of liposuction aspirates (fat stem cells).

Before you continue with this article, do you have questions about fat stem cell therapy, get help and information from our Caring Medical Staff

Adipose-derived stem cell therapy to treat chronic pain

There is a lot of controversy surrounding the use of adipose derived stem cells. This is a treatment that we almost never employ. The reason is that the we believe we can achieve similar results with much less invasive simple dextrose treatments.

While bone marrow has historically been used as a source of stem cells, adipose (fat)-derived stem/stromal cells (stromal cells are connective tissue cells) have been shown to have:

nearly identical fibroblast-like morphology and colonization (simply the ability of collagen-producing cells to multiple and repair cartilage and soft tissue damage),
immune phenotype (the immune system’s response to a specific injury. For example, you send cartilage cells to repair cartilage, you send bone cells to repair bone).

Autologous bone marrow stem cell volume is limited, but adipose tissue represents a large reservoir of stem cells. Research also supports as much as 500 to 1000 times as many mesenchymal and stromal vascular stem-like cells in adipose as compared to bone marrow. However, as the research below indicates, the number of stem cells is not always predictive of a positive healing outcome. Nor should this be a determinant in choosing any type of therapy.

In 2011, researchers in Finland published their research suggesting the benefits of Adipose stem cells, here are the take home points of that research published in the journal Stem Cell Reviews:

Adipose stem cells are an attractive and abundant stem cell source with therapeutic applicability in diverse fields for the repair and regeneration of acute and chronically damaged tissues.
Importantly, unlike the human bone marrow stromal/stem cells that are present at low frequency in the bone marrow, ASCs can be retrieved in high numbers from either liposuction aspirates or subcutaneous adipose tissue fragments.
In the laboratory, Adipose stem cells display properties similar to that observed in bone marrow stromal/stem cells including the ability to undergo at least osteogenic (bone repair mode) and chondrogenic (cartilage repair mode).1

Adipose-derived stem cell therapy techniques in treating chronic pain

As mentioned above, a patient researching fat stem cell injections will often ask “what’s the difference between your treatments and another type of fat stem cell treatment?” This is a difficult question to answer because we do not do all the other methods, we do our method of fat stem cell treatment that has evolved and been refined over the decades.

A better question to ask may be:

“How long has your office offered stem cell therapy?”, “How many patients have you seen?”

Our practice first started treating degenerative joint and spine patients with injectable non-surgical Prolotherapy solutions in 1957. At that time Dr. Gustav Hemwall became a leading pioneer and researcher in injectable regenerative treatments.
We have continued Dr. Hemwall’s legacy and have expanded Prolotherapy treatment to include blood platelets and stem cells from both bone marrow and adipose fat cells.
I, myself, have more than 25 years of experience in offering comprehensive Prolotherapy treatments.

All this experience has taught us that Prolotherapy should be involved in stem cell therapy. There are times when bone marrow serves a better purpose than fat stem cells and each patient presents a unique circumstance and stem cell therapy must remain flexible and adaptable to give the patient the best chance of achieving their goals of treatment.

Treating the whole joint to give Adipose-derived stem cell therapy its best chance of healing success

We will discuss at length the research that supports the use of Platelet Rich Plasma and Prolotherapy in support and augmentative procedures in fat stem cell treatments. Briefly:

In our office lipoaspirates or fat cells are combined with platelet rich plasma (PRP) from a blood draw or bone marrow retrieved from the iliac crest to augment healing.
This primary proliferant solution is then injected into the damaged, painful joint. As part of our comprehensive treatment program, the ligament and tendon attachments of the joint are also treated with dextrose Prolotherapy.

Treatment with Prolotherapy concurrent with stem cell treatment addresses the problem that the stem cell treatment may not. That is the repair of the joint instability which caused the osteoarthritis is the first place.

Reported treatment failures in patients receiving fat stem cell therapy and much of the medical literature describing less than anticipated or hoped for results in fat stem cell treatments ignore the underlying problems of joint instability.
It is ligament and tendon laxity that remains after stem cell therapy that causes joint instability.
- Joint instability is what caused wear to the cartilage and subchondral bone damage to the joint in the first place.
- While stem cell treatments can repair this damage, it cannot fully address the joint instability issues.
- The repair created by stem cell therapy is now jeopardized and compromised by abnormal grinding and movement of the joint. In essence the patient never left square one.
Prolotherapy makes stem cell treatment more effective by repairing the worn, stretched out ligaments and tendons. It stabilizes the motion in the joint and helps prevent a continuance of the wear and tear that called for stem cell treatments.
Dextrose Prolotherapy also provides nourishment for the stem cells and helps them grow and multiple. Please see my article Dextrose Prolotherapy stimulates stem cell growth

Whole joint Lipoaspirate Prolotherapy | Same-day fat stem cell therapy

Whole joint Lipoaspirate Prolotherapy treatment begins with collected fat stem cells. Lipoaspirates are obtained from the abdomen or love handle area through a quick liposuction procedure. The gentle liposuction takes a few minutes, and the whole time in the office is an estimated 60-90 minutes.

Lipoaspirate Prolotherapy is generally used in more severe cases of joint deterioration where a very strong proliferant solution may be a factor in speeding up the healing response. The main reason to use lipoaspirates as the proliferant in Prolotherapy is that adipose (fat) tissue contains an abundant population of stem cells.

Stem cells are self-renewing cells in our bodies which repair and replace old/damaged cells. Injecting these cells directly into the damaged tissue has been shown to enhance the integrity of the tissue and reduce pain.

Direct injection of fat stem cells

A September 2022 study from Showa University, Tokyo published in the Regenerative therapy (10) suggested that in animal research, injections of non-cultured or expanded adipose-derived stem cells could result in “meniscus regeneration.” The results indicate that adipose-derived stem cells will be useful in future clinical cell-based therapy strategies, including as a cell source for reconstruction of damaged knee menisci.

In reviewing the cumulative research of both animal and human studies, doctors at the Rizzoli Orthopaedic Institute in Italy, publishing in the journal Stem Cell International, found the injection of adipose-derived mesenchymal stem cell was first, safe and effective, and that secondly, several aspects favor the use of freshly harvested adipose-derived mesenchymal stem cell instead of expanded or cultured adipose-derived mesenchymal stem cell.

Let’s explore this research a little further. The researchers looked at 11 clinical studies. In these studies the application of fat stem cells into the knee was performed in many different ways including during arthroscopic knee procedures. This is what they found:

Ten out of the 11 clinical studies reported the use of non-expanded autologous adipose-derived stem cells.
Adipose tissue was obtained by liposuction from the abdominal area or buttocks in all cases, except for two studies where infrapatellar fad pad (knee) tissue was harvested during knee arthroscopy.
- However, in the studies where infrapatellar fad pad tissue was used, those studies’s authors concluded that more adipose-derived stem cells can be obtained from the buttocks than from infrapatellar fad pad, with the same differentiation potential in both sources.
All except three of these clinical papers described adipose-derived stem cells injected in varying volumes (3–5 cc) of autologous PRP, stimulated or activated with calcium chloride.
Three studies used hyaluronic acid as a carrier instead and one of them also added dexamethasone (an anti-inflammatory) to the stem cell-PRP-hyaluronic acid mixture.
After a single injection of adipose-derived stem cells, a variable number (usually 2) of PRP-only intra-articular injections were used in most of the studies.
In four of these studies, cells were injected following arthroscopic lavage and debridement.

All clinical studies showed that adipose-derived stem cells improve pain and functional scores at a follow-up of between 3 and 36 months.2

In three studies MRI analysis was performed, which revealed improved features, including increased cartilage thickness.

What does all this mean? Cultured vs. non-cultured cells? What is the number of stem cells needed for treatment?

What we have above is many different methods of delivering adipose-derived stem cells. All with varying degrees of success. However, the Italian research team noted that despite all the new data arising from these studies, the key concerns, such as the best amount of cells and the ideal scaffold (a scaffold in a medium that the stem cells can grow in) to be used, still remain unsolved.

In cultured adipose-derived mesenchymal stem cell treatment, the fat cells are cultured and grown outside the body. In research from the University of Pittsburgh the doctors found: “the use of cultured cells allows researchers to isolate and better characterize the desired cell type; however, economic and regulatory issues favor minimal manipulation procedures in the clinical practice.” 3 Other research suggests the opposite that culturing cells and the number of stem cells injected are a major focal point of the treatment.

In some instances of joint disease, doctors find that they want to expand the number of stem cells to create an accelerated healing environment. There is research to support this. There is also research to support that same day – non-cultured stem cell injections are just as effective and more importantly to the patient, provides a more simplified, less expensive, yet effective treatment.

This again was pointed out above in the research from the Italian research team. “. . . several aspects favor the use of freshly harvested adipose-derived mesenchymal stem cell instead of expanded adipose-derived mesenchymal stem cell.”2

The debate of course will continue.

In 2009 Dutch researchers found that the adipose fat stem cells found in stromal vascular fraction cells of the knee’s infrapatellar fat pad showed similar favorable characteristics as cultured adipose stem cells, and chondrogenic differentiation (cartilage regeneration) even appears to be slightly better.
- However, because of variable harvesting volumes and yields, SVF from the infrapatellar fat pad might only be applicable for the treatment of small focal cartilage defects, whereas for larger osteoarthritic defects subcutaneous adipose tissue would be preferable.4

In 2017, doctors writing in the Journal of Biomedical Science, gave this explanatory summary:

Due to the current regulatory environment, culture-expanded stem cells are considered to be a pharmaceutical product and require governmental clearance and approval.

Research examines the beneficial effects of Platelet Rich Plasma on adipose-derived mesenchymal stem cells.

Here is what Japanese researchers found in their published data in the journal Stem Cell Therapy and Research:

Because of their ease of isolation and relative abundance, adipose-derived mesenchymal stem cells are a particularly attractive autologous cell source for various therapeutic purposes.
Moreover, adipose-derived mesenchymal stem cells secrete a wide range of growth factors that can stimulate tissue regeneration.
However, the potential of adipose-derived mesenchymal stem cells differs depending on the donor’s medical condition, including diseases such as diabetes. Recent studies demonstrated that ASCs from diabetic donors exhibit reduced proliferative potential and a smaller proportion of stem cell marker-positive cells.

Platelet-rich plasma (PRP), which contains high levels of diverse growth factors that can stimulate stem cell proliferation and cell differentiation in the context of tissue regeneration, thus the co-transplantation of adipose-derived mesenchymal stem cells and PRP represents a promising novel approach for cell therapy in regenerative medicine and a promising approach in various fields of medicine and dentistry.6

Combining stem cells with Platelet Rich Plasma Therapy as a means to accelerate tissue regeneration in advanced degeneration has been the subject of numerous animal and human studies. 7,8,9

Comparing adipose-derived stem cells (ADSCs), PRP, and arthroscopic surgery

An October 2022 paper in the Journal of tissue engineering and regenerative medicine (11) offered a comparison of four treatments: The 1st: adipose-derived stem cells (ADSCs). The 2nd platelet-rich plasma (PRP). The third adipose-derived stem cells (ADSCs) + PRP, the 4th: Arthroscopy. The comparison was achieved by applying the questionnaires Western Ontario McMaster Universities, Short Form Health Survey 36 and Visual Analog Pain Scale, also by analyzing the synovial fluid (inflammatory cytokines, enzymatic, colorimetric and viscosity analysis), this evaluation happened in two moments: before the surgical procedures and after 6 months of the interventions and also was made a comparison to standard arthroscopy.

The questionnaires results showed a greater improvement in the scores of the domains analyzed in the adipose-derived stem cells (ADSCs) + PRP, followed by the adipose-derived stem cells (ADSCs) and then the PRP group.

Taking all the results into account, we infer that therapies with adipose-derived stem cells (ADSCs) and only adipose-derived stem cells (ADSCs) are safe and effective over 6 months for the improvement of pain, functional capacity and joint inflammation in volunteers with osteoarthritis. It is also considered that the use of adipose-derived stem cells (ADSCs) + PRP, particularly, is a promising alternative to help manage this disease, due to the better results presented among the four propose interventions.

All the healing elements in the body to travel through the blood, so using blood as a delivery vehicle makes sense

Platelet Rich Plasma has the ability to both increase stem cells and guide them in healing. In initial findings, PRP assisted stem cells in “figuring out” what they needed to be – whether a cartilage cell, or a bone cell, or a collagen cell for ligaments and tendons.

So the platelets are already attuned to provide a healing environment or scaffold to build on. In the research cited below results confirmed that PRP enhances MSC stem cell proliferation and suggested that PRP causes chondrogenic differentiation of MSC in vitro – in other words, the platelets told the stem cells what to do.

The platelets themselves secrete a variety of cytokines (proteins that regulate various inflammatory responses), including adhesive proteins and growth factors such as platelet-derived growth factor, transforming growth factor beta, vascular endothelial growth factor, basic fibroblast growth factor, Insulin-like growth factor-1 (IGF-1), and epidermal growth factor. All the healing elements in the body to travel through the blood, so using blood as a delivery vehicle makes sense.

Prolotherapy, PRP, and Adipose-derived stem cell therapy used in combination

In our experience, where the Prolotherapy injections are given is also an important factor, not just what is injected. This means that Stem Cell Therapy or Stem Cell Prolotherapy at Caring Medical includes not just a couple of injections of stem cell proliferants, but additionally, the whole joint/painful area is treated for underlying instability, which is likely the cause of the injury in the first place. If this aspect of the patient’s condition is not treated, we find that complete healing may not occur.

The treated area is typically stiff and swollen after the treatment because the desired effect is a temporary, localized inflammation to stimulate blood flow and growth factors in the area. A patient can return to work the same or next day. Our practitioners will help athletes return to exercise, generally within the week, and discuss possible modifications to encourage healing and minimize discomfort. The average number of treatments needed to achieve full healing is four to six, and each treatment is given four to eight weeks apart.

Like all medical conditions and therapies, each person responds individually. At the initial visit, your Prolotherapy specialist discusses how many treatments he or she feels will be needed to achieve the patient’s goals. An experienced Prolotherapy physician can give a reasonably accurate estimate. Because we see a lot of tough cases in our clinic who have failed numerous other treatments, sometimes it might be known upfront that Prolotherapy treatments could be needed for a full year or longer. Though this is rare, for a patient who is adamantly against surgery, or who has already failed surgeries, he or she may consider the time, energy, and money to use Stem Cell Prolotherapy worthwhile.

The first step is simple: Have a physical exam and consultation with an experienced practitioner. This way you will know what is the right Prolotherapy solution for you! At our treatment center, we utilize many individualized solutions and would love to evaluate your case to see if it sounds like we can help you.

Do you have questions about fat stem cell therapy, get help and information from our Caring Medical Staff

1 Lindroos B, Suuronen R, Miettinen S. The potential of adipose stem cells in regenerative medicine. Stem Cell Reviews and Reports. 2011 Jun 1;7(2):269-91.

2 Perdisa F, Gostyńska N, Roffi A, Filardo G, Marcacci M, Kon E. Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence.Stem Cells Int. 2015;2015:597652. Full research article

3. Liao HT, James IB, Marra KG, Rubin JP. The Effects of Platelet-Rich Plasma on Cell Proliferation and Adipogenic Potential of Adipose-Derived Stem Cells Tissue Eng Part A. 2015 Nov;21(21-22):2714-22.

4. Jurgens WJ, van Dijk A, Doulabi BZ, Niessen FB, Ritt MJ, van Milligen FJ, Helder MN.Jurgens WJ1, van Dijk A, Doulabi BZ, Niessen FB, Ritt MJ, van Milligen FJ, Helder MN. Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue. Cytotherapy. 2009;11(8):1052-64.

5. Pak J, Lee JH, Park KS, Park M, Kang L-W, Lee SH. Current use of autologous adipose tissue-derived stromal vascular fraction cells for orthopedic applications. Journal of Biomedical Science. 2017;24:9.

6. Tobita M, Tajima S, Mizuno H. Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness. Stem cell research & therapy. 2015 Nov 5;6(1):215. [Pubmed] [Google Scholar]

7. Simson J, Crist J, Strehin I, Lu Q, Elisseeff JH. An orthopedic tissue adhesive for targeted delivery of intraoperative biologics. J Orthop Res. 2012 Oct 23. doi: 10.1002/jor.22247. [Pubmed] [Google Scholar]

8. Xie X, Wang Y, Zhao C, Guo S, Liu S, Jia W, Tuan RS, Zhang C. Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration Biomaterials. 2012 Oct;33(29):7008-18. doi: 10.1016/j.biomaterials.2012.06.058. Epub 2012 Jul 19. [Pubmed] [Google Scholar]

9. Lin BN, Whu SW, Chen CH, Hsu FY, Chen JC, Liu HW, Chen CH, Liou HM. Bone marrow mesenchymal stem cells, platelet-rich plasma and nanohydroxyapatite-type I collagen beads were integral parts of biomimetic bone substitutes for bone regeneration. J Tissue Eng Regen Med. 2012 Jun 28. doi: 10.1002/term.1472. [Pubmed] [Google Scholar]
10 Itose M, Suzawa T, Shibata Y, Ohba S, Ishikawa K, Inagaki K, Shirota T, Kamijo R. Knee meniscus regeneration using autogenous injection of uncultured adipose tissue-derived regenerative cells. Regenerative Therapy. 2022 Dec 1;21:398-405. [Google Scholar]
11 Schweich‐Adami LC, da Silva RA, da Silva Menezes JN, Baranoski A, Kassuya CA, Bernardi L, Oliveira RJ, Antoniolli‐Silva AC. The intra‐articular injection of adipose‐derived stem cells decreases pain and reduces inflammation in knee osteoarthritis, with or without the addition of platelet‐rich plasma also improves functionality. [Google Scholar]

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