- 1 Stem Cell & PRP Therapy for Cartilage Regeneration
- 1.1 Mechanism of Cartilage Regeneration
- 1.2 Clinical Applications of Adipose Derived Stem Cells
- 1.3 Isolation and Application of Platelet Rich Plasma
- 1.4 Scientific Evidence for Adipose Derived Stem Cell Regeneration of Cartilage in Humans
- 1.5 Our Clinical Research & Treatment of Degenerative Joint Disease and Osteoarthritis
- 2 Stem Cell & PRP Therapy for Chronic Back Pain (Degenerative Disc Disease)
Stem Cell & PRP Therapy for Cartilage Regeneration
Articular cartilage repair remains a significant challenge in orthopedics. This has led to increased interest in stem cell-based therapies for tissue engineering, or regenerative medicine and musculoskeletal applications. Fat or “Adipose tissue” derived stem cells (ADSCs) in the form of stromal vascular fraction (SVF) offer certain advantage:
- Adipose derived stem cells are easy to isolate in large numbers by liposuction.
- Adipose derived stem cells are self-regenerating and have a high expansion potential.
- ADSCs are capable of differentiating into several different cell lines, including cartilage, tendon, bone and ligament.
Mechanism of Cartilage Regeneration
Although the exact mechanism of cartilage repair and regeneration is not fully understood, stem cells are known to be involved in this process by:
- Adipose stem cells secret cytokines, chemokines, growth factors, and exosomes which stimulate microvascular growth, collagen production, and cellular repair.
- Stem cells that are introduced into the diseased joints by injection may actually become engrafted into the tissue, and differentiate into tissue specific cells, such as cartilage, blood vessels, etc.
- Most likely, it is a combination of direct action of stem cells and their indirect stimulation of other cells by their signaling secretions.
Clinical Applications of Adipose Derived Stem Cells
Recent advances in the field of tissue engineering seek to combine mesenchymal stem cells, growth factors, and biomaterial scaffolds (the so-called tissue engineering triad), to create functional cartilage tissue replacement. Non-cultured expanded ADSCs in the form of SVF, combined with Platelet Rich Plasma (PRP), and hyaluronic acid (HA), have recently been used in humans to treat osteoarthritis and other musculoskeletal abnormalities. Hyaluronic acid is a naturally occurring scaffolding material. It has a high affinity for cartilage defects and provides an environment for stem cells to adhere to the lesion and differentiate.
Isolation and Application of Platelet Rich Plasma
PRP consists of autologous blood with concentrations of platelets above baseline values. It is created through a two phase centrifugation process called plasmapheresis, in which plasma and platelets are separated from red blood cells and white blood cells. After this process, the PRP serum contains high concentrations of protein growth factors, such as platelet derived growth factor, vascular endothelial growth factor, endothelial cell growth factor, fibroblast growth factor, epidermal growth factor, transforming growth factor β1, thrombospondin-1 and insulin-like growth factor. These PRP protein factors have been shown to be critical in joint repair.
Scientific Evidence for Adipose Derived Stem Cell Regeneration of Cartilage in Humans
- In 2011, Pak et al. successfully treated patients with osteoarthritis of the knees by using autologous ADSCs in the form of SVF along with platelet rich plasma (PRP) and hyaluronic acid (HA). He was able to document the regeneration of cartilage-like tissue in these patients through Magnetic Resonance Imaging (MRI) studies. In 2013, Pak et al. treated patients with chondromalacia patella of the knee with ADSCs, PRP, and HA. After three months of treatment, patients showed clinical improvement, and positive regeneration of hyaline-cartilage-like tissue at the patellofemoral joints. In 2014, Pak treated a patient with a documented meniscal tear of the knee. The patient was treated with SVF containing ADSCs, PRP, and HA. After three months, the patient documented clinical improvement, and the meniscus tear had improved, if not entirely disappeared in subsequent follow-up MRIs after three months.
- In 2012, Koh et al., treated 18 patients with osteoarthritis of the knees. ADSCs were percutaneously injected into the knees with activated PRP after arthroscopic debridement. The whole organ MRI scores, particularly the cartilage whole organ MRI score improved. The authors concluded that improvements in the clinical and MRI results were positively related to the number of ADSCs injected. In 2015, Koh published a study involving 30 patients with osteoarthritis of the knees. They were injected with SVF containing ADSCs, and PRP under arthroscopic guidance. At a minimum of two years after the operation, almost all patients showed significant improvement in knee injury. In a second-look arthroscopy, 63% had improved cartilage, 25% had maintained their cartilage, and 12% had failed in healing their cartilage defects.
- The very first double-blind, randomized clinical trial involving ADSCs were published in 2014. The ADSCs were injected and involved three separate groups with low-dose, mid-dose and high-dose stem cells. The regeneration of the cartilage was confirmed by MRI and arthroscopy. Furthermore, the histology of the regenerated tissue was consistent with hyaline cartilage in characteristics. This study clearly showed that ADSCs are effective in regenerating cartilage, and that higher dosage of ADSCs were more efficacious than a lower numbers in regenerating cartilage.
- The most recent study published in January 2017 by Nguyen et al., included 30 patients with grade II or III osteoarthritis. The placebo group consisted of 15 patients, and the treatment group consisted of 15 patients. In the treatment group, the SVF was suspended in PRP before being injected into the joint. Patients were evaluated 6, 12, and 18 months status-post treatment. Treatment efficacy was significantly different between placebo and treatment groups. All treatment group patients had significantly reduced pain scores and increased functional scores. The findings of this study suggest that SVF/PRP injection efficiently improved osteoarthritis for 18 months after treatment. Per the authors of this study, the patients will be continually monitored for an additional 24 months.
Our Clinical Research & Treatment of Degenerative Joint Disease and Osteoarthritis
Currently, there is no cure for painful osteoarthritis in stage II and stage III. For these patients, the intra-articular injection of ADSCs in the form of SVF, with PRP, can be efficacious in symptom improvement and cartilage regeneration. The addition of hyaluronic acid as a scaffolding agent may also be helpful.
Stem Cell & PRP Therapy for Chronic Back Pain (Degenerative Disc Disease)
Degenerative disc disease (DDD) is a condition associated with the degeneration of one or more of the discs in the spine. It can result in severe chronic pain in the low back which can radiate to the hips and legs. A series of therapies have been developed to treat DDD, including physical therapy, chiropractic, acupuncture, and surgical intervention. However, the therapeutic results of such treatments have remained insufficient.
Can Stem Cells Help Back Pain and Degenerative Discs?
Recent studies have focused on the use of adult stem cell-based therapies for DDD. Adipose derived stem cells (ADSCs) in the form of stromal vascular fraction (SVF) injected into the nucleus pulposus of the degenerated intervertebral discs appears to be effective in the treatment of DDD.
Currently, the mechanism of regeneration is not completely clear:
- It could be due to the secretory effects of the stem cells injected, as adipose stem cells excrete a variety of cytokines, chemokines, growth factors, and exosomes;
- It could be due to direct engraftment and differentiation of the stem cells that were introduced into the degenerated and diseased discs, as there is evidence that stem cells injected may actually become engrafted into the tissue, and differentiate into tissue specific cells; or
- It could be due to the combination of secretory effects and direct engraftment of stem cells.
- In 2015, Song et al. demonstrated that ADSCs are able to stimulate matrix synthesis and cell proliferation of degenerated nucleus pulposus cells, thus promoting the restoration of damaged nucleus cells in a degenerated disc.
- In 2015, Pettine et al. reported on the use of adult stem cells to treat discogenic low back pain as an alternative to surgery. The stem cells were injected directly into the nucleus pulposus with no complications reported. Results of this study demonstrated a 71% reduction in pain and 64% improvement in disability rating. Over 81% of the patient’s avoided surgery through the two years of the study. Platelet rich plasma (PRP) has also been studied as a treatment for degenerative disc disease of the spine. PRP is a sample of autologous blood with concentrations of platelets above baseline values. It is created through a two phase centrifugation process called plasmapheresis, in which plasma and platelets are separated from red blood cells and white blood cells. After this process, the PRP serum contains high concentrations of protein growth factors, such as platelet derived growth factor, vascular endothelial growth factor, endothelial cell growth factor, fibroblast growth factor, epidermal growth factor, transforming growth factor β1, thrombospondin-1 and insulin-like growth factor. These PRP protein factors have been shown to be critical in tissue repair.
- In 2016, Tuakli-Wosornu et al. undertook a study to determine whether a single injection of PRP into symptomatic degenerative intervertebral discs will improve patient reported pain and function. Results of this study indicated there were statistically significant improvements in patients who received intradiscal PRP with regard to pain, function, and satisfaction, compared to controls. However, although PRP offers autologous growth factors, it does not provide any stem or progenitor cells.
- In 2017, Kristin et al. evaluated the safety and efficacy of administering both SVF and PRP intradiscally into patients with DDD. Patients demonstrated statistically significant improvement in several parameters, including flexion, pain ratings, and short form questionnaires. Additionally, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the procedure.
Our Clinical Research & Treatment of Degenerative Disc Disease and Chronic Back Pain
Based on the safety and success of intradiscal injection with stem cells and PRP as documented in published studies, the Stem Cell Institute of Los Angeles offers this procedure to patients with chronic back pain caused by degenerative disc disease.