November 18, 2019
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Review of Amniotic Fluid Injections

Advertisements in newspapers and magazines publicize stem cell injections with claims that are often times not backed up with medical evidence. Nomenclature can be confusing, but stem cell injections range from adipose derived stem cells, bone marrow derived stem cells and amniotic fluid stem cells. The goal of a stem cell injection is to inject a cell with differentiation potential and cause the release of growth factor and immune regulatory cells (Adam Anz, 2014). For the purpose of this review, we will look at the evidence behind amniotic fluid stem cell injections.

Background

Amniotic stem cell injections are obtained from human placentas. Amniotic fluid is found within the amniotic cavity and helps protect the developing fetus (Coppi, 2019). Studies have shown that amniotic fluid in vivo does contain live stem cells (Alberto Panero, 2019). One advantage of embryonic stem cells verse adult stem cells is that they are pluripotent and can differentiate all adult cell types (Robert LaPrade, 2016). Another benefit of amniotic fluid injections is that they have been found to contain multiple different growth factors (Jonathan Riboh, 2015). The process of harvesting amniotic stem cells for an injection involves removing the amion and adding digestive agents (trypsin and collagenase) to help free up the amniotic mesenchymal stem cells (Natasha Topoluk, 2018). After the cells have been isolated, they are typically frozen and then thawed out prior to the procedure. The collection of the amniotic cells occurs after delivery (Jonathan Riboh, 2015). The amniotic cell injections hold an advantage over the bone marrow or adipose derived because they do not require an invasive cell harvest (Jonathan Riboh, 2015).

One concern in the use of amniotic fluid injections is in preventing the spread of infection. There is a difference in the infection risk between fresh and preserved amniotic membrane product (Jonathan Riboh, 2015). The reason amniotic fluid injections are cryopreserved is because a fresh amniotic membrane transplant has been shown to have an infection rate of 8% (Jonathan Riboh, 2015). Within the amniotic fluid, bacteria are thought to be in an active incubation period and seroconvert after incubation (Jonathan Riboh, 2015). Due to the concern for infection, all amniotic membrane fluid is cryopreserved to prevent bacterial seroconversion (Jonathan Riboh, 2015). However, the cryopreservation process itself can alter the properties of the amniotic fluid. A study in 2011 published in Cryobiology looked at the effects on the isolated cells during different preservation. What they found was that cryopreservation did not affect endothelial cell attachment, which is thought to be important in the success of a stem cell injection (Hassan Niknejad, 2011).
amniotic fluid stem cell injection

Image 1. Demonstration of amniotic fluid injection of the knee (courtesy of weil)

Musculoskeletal role

The goal of an amniotic fluid injection is to deliver mesenchymal stem cells into a given media (joint, tissue, etc.) where they can differentiate into cartilage or provide growth factors that stimulate healing within a damaged tendon. The hope is that these pluripotent stem cells can help create new cartilage or muscle (Coppi, 2019)

A study published in the American Journal of Sports Medicine looked at whether there were live mesenchymal stem cells and growth factors in 3 commercially available Amniotic Fluid Products (Alberto Panero, 2019). The three amniotic products they evaluated were found to have no mesenchymal stem cells (Alberto Panero, 2019). They were able to find multiple cytokines and growth factor within the amniotic injection (Alberto Panero, 2019). Some of these growth factors and cytokines that have been isolated from amniotic fluid include platelet derived growth factor, IL-8, and Hyaluronan (Alberto Panero, 2019).

There is a paucity of literature on human recipients of amnion derived injections. Published in Arthritis Research & Therapy in 2014, researchers injected an amniotic/chorionic injection into rats with osteoarthritis and evaluated their capabilities as a disease modifying agent. This study shows promise because the group injected with the amnion/chorion had fewer erosions and cartilage degeneration (N WIllett, 2014).

There are also studies that look at the role of amnion derived cells in chronic tendon issues. In 2014 in Foot & Ankle International, researchers looked at the role of cryopreserved amniotic membrane injections in patients with plantar fasciitis. They randomized a group of patients with plantar fasciitis to receive a corticosteroid injection or a cryopreserved amniotic membrane injection (Andrew Hanselman, 2014). Then at 6 weeks, they were offered a second injection if they had not experienced pain relief. What they found was that in patients who required a single injection, those who received a corticosteroid injection had better pain relief at 6 weeks. However, in the group that received two injections, the stem cell group had better pain relief at 18 weeks (Andrew Hanselman, 2014).

Conclusion

Overall, amniotic derived stem cell injections show promise in their role in treating cartilage damage and chronic tendon damage. We know that in utero amniotic fluid does contain mesenchymal stem cells, but that in the study we highlighted by Panero, these cells were not found on the commercially available products they analyzed. One of the further challenges we found in our literature review is that most of the studies were done on animal models and not humans. Further analysis is needed on the other commercially available amniotic fluid products and future research is needed as to their role in chronic joint and tendon degeneration.

Bibliography

Adam Anz, J. H. (2014). Application of Biologics in the Treatment of the Rotator Cuff, Meniscus, Cartilage, and Osteoarthritis. The Journal of the American Academy of Orthopaedic Surgeons, 68-79.

 

Alberto Panero, A. H. (2019). Are Amniotic Fluid Products Stem Cell Therapies? The American Journal of Sports Medicine, 1230-1235.

 

Andrew Hanselman, J. T. (2014). Cryopreserved Human Amniotic Membrane Injection for Plantar Fasciitis: A Randomized, Controlled, Double-Blind Pilot Study . Foot & Ankle International.

 

Coppi, P. D. (2019). Stem Cells from the Amion. In R. L. Anthony Atala, Principles of Regenerative Medicine (pp. 133-148). Elsevier.

 

Hassan Niknejad, e. a. (2011). The effects of preservation procedures on amniotic membrane’s ability to serve as a substrate for cultivation of endothelial cells. Cryobiology, 145-151.

 

Jonathan Riboh, B. S. (2015). Human Amniotic Membrane-Derived Products in Sports Medicine. The American Journal of Sports Medicine, 2425-2434.

 

N WIllett, T. T. (2014). Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development. Arthritis Research & Therapy.

 

Natasha Topoluk, K. S. (2018). Amniotic mesenchymal stem cells mitigate osteoarthritis progression in a synovial macrophage-mediated in vitro explant coculture model . Journal of Tissue Engineering and Regenerative Medicine, 1097–1110.

 

Robert LaPrade, J. D. (2016). AAOS Research Symposium Updates and Consensus: Biologic Treatment of Orthopaedic Injuries. Journal of the American Academy of Orthopaedic Surgeons, e62-e78.

 

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