Ross Hauser, MD; Danielle Matias, PA-C; Demi Foster, APRN

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

Liopgems are better understood as an FDA-approved device that may make it easier for your doctor to inject adipose stem cells.

• In the Lipogem procedure, lipoaspirate or liposuction is done into the “love handles,” or fatty areas of the abdomen. A possible drawback with lipoaspiration is that it is challenging to do in a person who has very little body fat.
• The adipose or fat tissue is then cleaned or processed in a “kit,” which makes the injection more tolerable to the patient in the form of a “micro fragmented fat,” perhaps one way to describe this would be a less chunky injection solution.

While bone marrow has historically been used as a source of stem cells, adipose (fat)-derived stem cells have been shown in some research to have:

• nearly identical fibroblast-like morphology and colonization (simply the ability of collagen-producing cells to multiply 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).

Writing in the journal Stem cell reviews and reports, researchers in 2011 reviewed possible benefits of Adipose stem cells. Here are the take-home points of that research published in the journal Stem Cell Reviews (1):

• 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.
• 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).
• Adipose stem cells may be retrieved in high numbers from either liposuction aspirates or subcutaneous adipose tissue fragments, making their stem cells more abundant in some cases than bone marrow stem cells.

Direct injection of fat stem cells 

In reviewing the cumulative research of both animal and human studies, doctors at the Rizzoli Orthopaedic Institute in Italy, published in the journal Stem Cell International, (2) found the injection of adipose-derived mesenchymal stem cells 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. (Due to the current regulatory environment, culture-expanded stem cells are considered to be a pharmaceutical product and require governmental clearance and approval. Therefore expanded or cultured adipose-derived mesenchymal stem cells are an unapproved and unregulated procedures and cannot be offered in the United States.)

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

A June 2022 study led by Charles Sturt University in Australia and published in the journal Regenerative Medicine (3) offered a large two-year prospective study on the long-term safety and effectiveness of adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis.

In this study, 329 patients with knee osteoarthritis underwent intra-articular adipose-derived mesenchymal stem cell therapy. The patients were then followed up for 24 months and were separated based on the severity of their knee osteoarthritis.

The published results of this study were:

• “Treatment was well tolerated with no related serious adverse events.
• All participant groups reported clinically and statistically significant pain improvement.
• Clinical outcome was not influenced by patients’ age or BMI (obese, overweight, normal weight, underweight).”
• Conclusion: adipose-derived mesenchymal stem cell therapy is an effective, safe, and long-lasting treatment option for knee osteoarthritis with the potential to delay total joint replacement.

Five year follow-up on adipose-derived (AD) MSCs reported in the medical literature

In May 2022, doctors in South Korea writing in the journal Stem Cells Translational Medicine (4) wrote: “Although successful short-term results of the intra-articular injection of mesenchymal stem cells (MSCs) for the conservative treatment of knee osteoarthritis have been reported, the mid-term results of the injection of adipose-derived (AD) MSCs remains unknown.” To add to the research on mid-term results, or in this case five year out study, the researchers assessed eleven patients with knee osteoarthritis who received a single intra-articular injection of autologous high-dose adipose-derived mesenchymal stem cells. The researchers found: “A single intra-articular injection of autologous, high-dose ADMSCs provided safe and clinical improvement without radiologic aggravation for five years. Furthermore, structural changes in the osteoarthritic knee showed significant improvement up to three years, suggesting a possible option for disease-modifying outpatient treatment for patients with knee osteoarthritis.”

A May 2023 study in the Journal of orthopaedic surgery and research (5) compared autologous mesenchymal stem cells injections from bone marrow cells and adipose-derived stromal cells for alleviating symptoms of knee osteoarthritis. In this study 51 patients undergoing a single intra-articular injection of bone marrow aspirate concentration and 51 patients undergoing a single intra-articular injection of adipose-derived stromal cells were followed. What the researchers found was that both treatments provided similar positive pain, function and quality of life outcomes in  patients one month and six months following the injection. Patients who had osteoarthritis Kellgren and Lawrence grades 1 & 2 (onset to moderate) faired better than patients with Kellgren and Lawrence grades 3 & 4 (more severe). Conclusion: “Both intra-articular BMAC and ADSC injections significantly improved pain and functional outcomes at 6-month follow-up in patients with knee osteoarthritis. The difference between bone marrow aspirate concentrate and adipose-derived stromal cells groups as tissue sources of MSCs was not statistically significant in terms of clinical and functional outcomes.”

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

An October 2022 paper in the Journal of tissue engineering and regenerative medicine (6) 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, and the 4th: Arthroscopy. The researchers found that taking all the results into account, therapies with adipose-derived stem cells (ADSCs) and adipose-derived stem cells (ADSCs) by themselves 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 proposed interventions.

Research comparing PRP, Bone Marrow, and Adipose-Derived Stem Cells. Results: They all worked well.

A July 2020 study published in the journal Clinical Medicine Insights Arthritis and Musculoskeletal Disorders, (7) compared Platelet-Rich Plasma (PRP), bone marrow aspirate concentrate, and adipose-derived mesenchymal stem cell (MSC) injections in the treatment of osteoarthritis of the knee using functional scores.

• Methods: A total of 89 patients with painful knee osteoarthritis were included in this study.
• Patients were assigned to one of the 3 treatments according to the severity of osteoarthritis as indicated by symptoms and radiography to PRP (stage I osteoarthritis), bone marrow aspirate concentrate (stage II osteoarthritis), or adipose-derived MSC (stage III osteoarthritis).
• Clinical assessment was performed using standard scoring systems, Surveys were completed at preoperative, and at 90, 180, and 265 days post-treatment.

Results: They all worked well.

• In a general statement, the PRP worked just as well in stage 1 knee osteoarthritis patients as the bone marrow aspirate worked in stage 2 knee osteoarthritis patients and the adipose-derived stem cells worked for stage 3 knee osteoarthritis patients. To quote the researchers: “Our findings support previous reports and encourage further research on the use of these cost-effective treatments for osteoarthritis of the knee.”

This is also a validation of our policy of not going straight to stem cell therapy in some of our patients. PRP or Prolotherapy, can provide equally good results without the added expense.

More articles

Prolotherapy Knee Injections : Prolotherapy is a non-surgical injection treatment that introduces small amounts of an irritant solution (simple dextrose) into the knee with the goal of helping the immune system rebuild the soft connective tissue of the knee ligaments and knee tendons to restore stability to the knee and alleviate pain and improve function. The research is well documented and will be presented below. Prolotherapy does not work for every patient.

Chronic Knee Pain and Knee Instability : In this article, we will discuss the degenerative knee disease process that leads to knee instability. We will spend some time talking about the knee ligaments. As you will see in the research and clinical case histories below. The knee ligaments are often the most over looked, unless you have a ACL or other ligament rupture, component of knee instability.

When stem cell therapy will not work for your knee pain : If you are reading this article, it is very likely that you are exploring stem cell therapy for your degenerative knee condition or for the knee problems or surgical recommendations of knee replacement for a loved one. Either you or your loved one is in a lot of pain now, and maybe right now is not the right time to get a knee replacement. When opting for regenerative medicine injections, providers and patients have to have a realistic idea of just how effective or ineffective these treatments can be.

The regeneration of articular cartilage with prolotherapy | Caring Medical Research

References

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