Research supporting PRP combined use of PRP and stem cells

Ross Hauser, MD explains using Stem Cell Therapy and Platelet Rich Plasma Therapy as a combination treatment.

Stem cell therapy or stem cell Prolotherapy is a non-surgical injection treatment utilizing the patient’s stem cells to accelerate healing.

Platelet Rich Plasma Therapy (known as PRP) is also a non-surgical injection treatment. It differs from stem cells in that it uses the healing factors found in blood plasma to heal degenerative or acute damage in joints. For a detailed discussion on the use of PRP, please read my article What is Platelet Rich Plasma Therapy?

One of the most frequent questions we answer is why not use stem cell therapy for every patient with osteoarthritis and joint degeneration?

It is in the best interest of the patient to use simple treatments if simple treatments will do the job of achieving the patient’s goal of healing

Of our treatment options Prolotherapy injections are the simplest. In more difficult cases we may introduce Platelet Rich Plasma or PRP Prolotherapy and for cases where warranted Stem Cells. If we get to a situation where we decide to use stem cell therapy, we augment this treatment with Prolotherapy and PRP, and sometimes a combination treatment using bone marrow stem cells and fat derived stem cells.

These treatments, used in combination, are designed to treat the entire joint as opposed to an isolated injury. Please see my article on Why stem cells did not work for my knee pain, for a discussion of why it is best, in our opinion to use Prolotherapy, PRP, and stem cells in combination.

Combining stems cells with Platelet Rich Plasma Therapy

Combining stems 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.

In a 2017 study, data published in the Journal of Translational Medicine showed that stromal vascular fraction cells (where a source of fat derived stem cells are found) freshly isolated from adipose tissue, combined with PRP and administered intra-articularly (injections), demonstrate healing potential in patients with degenerative osteoarthritis.

The researchers noted “This is consistent with previously published results from both preclinical and clinical studies. Patients demonstrated significant improvements in their degenerative osteoarthritis leading to a better quality of life. These improvements included a clinically significant reduction in pain.”

The studied showed:

Pain functional status of osteoarthritic knees were improved 12 months post injection in all patients and this improvement was maintained at the 2 year time point.
Some patients showed improvements as early as 3 and 6 months after the injection of SVF and PRP.
- This confirms the mechanism of action of regenerative medicine to be a cascade of events that occur over time.
- These events include an immuno-modulatory effect (Regulating the immune system) that can lead to tissue remodeling.
- The anti-inflammatory and pain reduction effects may be attributed to the soluble growth factors secreted from the stem cells.
- The stem cell and PRP injections also significantly reduced the requirement of pain medication in 8 out of 10 patients.
- The researchers were able to demonstrate safety with no serious side effects reported during the 2 year follow-up.

The conclusion of this research: SVF (adipose stem cell) combined with PRP has a great potential as a therapeutic agent in regenerative medicine especially in orthopedic conditions.1

The idea of using PRP as a bed or scaffold for stem cells to grow in has been researched for many years. In a 2012 study doctors at the Shanghai Jiaotong University School of Medicine in China suggested that PRP is a candidate bioactive scaffold capable of releasing endogenous growth factors and that bone marrow stem cells and adipose derived stem cells seeded within the PRP scaffold were able to change into chondrocytes (cartilage building blocks) suitable for cell-based cartilage repair.2

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.

New and recent research on combining PRP and stem cell therapy

Researchers in Tokyo tested and showed that platelet rich plasma (PRP) to be an effective medium that mesenchymal stem cells grew more quickly in.4 This research was supported more recently by animal studies,5 and in various research studies which is testing various “PRP nutrient gels” for various healing growth factors to take root in. 6

Doctors at the Sungkyunkwan University School of Medicine, Seoul, Korea suggest in a new study from January 2017 that bone marrow aspirate concentrates and platelet-rich plasma (PRP) are effective for tendinopathy and rotator cuff tendon tear.7 This follows on earlier research from University School of Medicine doctors who found stimulating bone marrow to release stem cells combined with a biomateral scaffold patch on the site of huge surgical incisions significantly reduced retear and high surgical failure rates in the arthroscopic repair of massive rotator cuff tears.8

Doctors at the Hospital for Special Surgery in New York say in their animal studies bone marrow stem cells accelerated healing after arthroscopic surgery at the bone/tendon interface.9

A new study from October 2016 found that PRP manages the repair and regeneration of damaged articular cartilage in the joints and delays the degeneration of cartilage by stimulation stem cells to get to the site of an injury, multiply once they get there, and then change into the bone, cartilage or soft tissue cells needed to repair the joint.10

Another study from September 2016 found that PRP combined with bone marrow stem cells promoted difficult to treat tendon-bone healing in a rabbit model.11

Doctors in China writing in the Journal of tissue engineering and regenerative medicine wrote that platelet rich growth factors significantly enhanced cell DNA synthesis (cell replication) improved viability and promoted proliferation, while facilitating cell migration and the recruitment of tendon-derived stem cells. In other words, PRP promoted the creation and multiplication of stem cells.12

Doctors in Turkey found: “The use of PRP and MSCs provides hope for the treatment of Achilles tendon ruptures that limit human beings’ functionalities and quality of life, particularly for athletes. It is thought that the use of MSC can be more effective for tendon healing.”13

In a patient given a total knee replacement or hip replacement surgical date who is anxious to avoid surgery, an aggressive combined treatment healing program may be designed.

Here is where stem cells may be introduced. Stem cells have unique talents to repair cartilage and bone damage. They can differentiate or change themselves into the raw material to rebuild bone and soft tissue. When injected into a damaged area they signal the native healing and inflammatory cells in the joint and jump start the immune system’s rebuilding process. These signals are received by the blood plasma cells and confirmation signals are sent back.

This starts the healing cascade. Sometimes in an injury depleted joint more plasma cells are needed to fix or rebuild the communication network and to provide growth and healing factors.

References for this article

1 Bansal, H., Comella, K., Leon, J., Verma, P., Agrawal, D., Koka, P., & Ichim, T. (2017). Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis. Journal of Translational Medicine, 15, 141. [Pubmed] [Google Scholar]

2. 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]

4. Tobita M, et al. Adipose tissue-derived mesenchymal stem cells and platelet-rich plasma: stem cell transplantation methods that enhance stemness. Stem Cell Res Ther. 2015; 6: 215. [Pubmed]
5. Tang HC et al. Differentiation Effects of Platelet-Rich Plasma Concentrations on Synovial Fluid Mesenchymal Stem Cells from Pigs Cultivated in Alginate Complex Hydrogel. Int J Mol Sci. 2015 Aug 7;16(8):18507-21. doi: 10.3390/ijms160818507. [Pubmed]
6. Jalowiec JM et al. An in vitro investigation of PRP-gel as a cell and growth factor delivery vehicle for tissue engineering. Tissue Eng Part C Methods. 2015 Oct 15. [Pubmed]
7 Kim SJ, Song DH, Park JW, Park S, Kim SJ. Effect of Bone Marrow Aspirate Concentrate Platelet-Rich Plasma on Tendon Derived Stem Cells and Rotator Cuff Tendon Tear. Cell Transplant. 2017 Jan 20. doi: 10.3727/096368917X694705. [Pubmed]
8 Degen RM, Carbone A, Carballo C, Zong J, Chen T, Lebaschi A, Ying L, Deng XH, Rodeo SA. The Effect of Purified Human Bone Marrow-Derived Mesenchymal Stem Cells on Rotator Cuff Tendon Healing in an Athymic Rat. Arthroscopy. 2016 Dec;32(12):2435-2443. doi: 10.1016/j.arthro.2016.04.019. [Pubmed]
9 Yoon JP, Chung SW, Kim JY, Lee BJ, Kim HS, Kim JE, Cho JH. Outcomes of Combined Bone Marrow Stimulation and Patch Augmentation for Massive Rotator Cuff Tears. Am J Sports Med. 2016 Apr;44(4):963-71. doi: 10.1177/0363546515625044. Epub 2016 Feb 5. [Pubmed]
10. Sakata R, Reddi AH. Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration. Tissue Eng Part B Rev. 2016 Oct;22(5):408-419. [Pubmed]
11. Teng C, Zhou C, Xu D, Bi F. Combination of platelet-rich plasma and bone marrow mesenchymal stem cells enhances tendon–bone healing in a rabbit model of anterior cruciate ligament reconstruction. Journal of Orthopaedic Surgery and Research. 2016;11(1):96. doi:10.1186/s13018-016-0433-7. [Pubmed]
12 Xu K, Al-Ani MK, Sun Y, et al. Platelet-rich plasma activates tendon-derived stem cells to promote regeneration of Achilles tendon rupture in rats. J Tissue Eng Regen Med. 2017 Apr;11(4):1173-1184. doi: 10.1002/term.2020. [Pubmed]
13 Yuksel S, Guleç MA, Gultekin MZ, Adanır O, Caglar A, Beytemur O, Küçükyıldırım BO, Avcı A, Subaşı C, İnci Ç, Karaoz E. Comparison of the Early-Period Effects of Bone Marrow-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma on Achilles Tendon Ruptures in Rats. Connect Tissue Res. 2016 May 18. [Pubmed]

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