Amniotic Stem Cells

Learn More About How Human Amniotic Membrane, Tissue, and Fluid may Help You!

Amniotic Stem Cell Therapy Overview

The historical use of various clinical applications of amniotic membranes began relatively early in the 20th century. The first applications were in wound healing, followed by a large variety of other applications, including use in musculoskeletal conditions. More recently, applications have been described as using umbilical cords and various other combinations of birth tissue. The use of amniotic fluid as a treatment for orthopedic conditions was recorded as early as 1938.

Amniotic fluid has a variety of homologous uses as in utero it naturally functions to protect and cushion, reduce inflammation and enhance mobility. It is a dynamically changing biological fluid that changes in both volume and composition throughout the course of gestation and the fluid normally ranges from 25 mL at 10 weeks to about 400 mL at the time of delivery.
Composition of amniotic fluid. Key elements of amniotic fluid include growth factors, carbohydrates, proteins, lipids, electrolytes, and other nutrients, as well as hyaluronic acid (HA), a principal component of viscosity and lubrication in synovial fluid.
Functions of the amniotic fluid in utero include:
  • An extension of the fetal extracellular compartment.
  • A connection between the intracoelemic and extracoelemic components of the developinginfant.
  • A physiologic buffer for various extra-fetal compounds.
  • Modulation of fluid and electrolyte transport between the mother and fetus across fetal andplacental membranes.
  • Nutritional support of the fetus.
  • Provision of a supportive fluid cushion to the developing fetus, allowing fetal movement andgrowth.
  • Protective functions provided by the inclusion of multiple growth factors and biologicalmolecules.
  • Provide antimicrobial effectors that protect the fetus

Stem Cells from Bone Marrow Aspirate


Concentrations of the various composition of amniotic fluid vary over the course of gestation, frequently changing near the time of delivery. Actual measurements of concentrations have been done for some of the components as follows:

Sozanskii measured the concentrations of various compounds in pregnancy and compared serum and AF concentrations. He found that “in 136 women at various terms of pregnancy…the biochemical composition of amniotic fluid changed as follows: there was a rise of urea, rest nitrogen, and of the total protein; sugar concentration dropped; chloride level remained unchanged.”
Campbell did a similar measurement set and found comparable results. “Levels of sodium, potassium and bicarbonate were significantly higher in amniotic fluid whilst chloride, urea, bilirubin, protein, albumin, glucose, creatinine, calcium and phosphate were present in higher concentrations in extraembryonic coelomic fluid. All differences in concentration were significant (P less than 0.05; unpaired t-test). No relation was demonstrated between electrolyte concentrations in amniotic fluid or coelomic fluid and stage of gestation.”

Biological activity

Many of the above compounds and substances have well characterized biological activities. While the exact mechanism of activity is known for individual compounds, the subtle interrelationship of how these agents interact is continuously being researched. Further, various pathologic states have been associated with dysregulation of the amounts and concentrations of these materials.

Studies with Amniotic Fluid

Burns, et al., looked at the concentration of various inflammatory cytokines in amniotic fluid:6
“In this study, we examined matched samples of term maternal blood, cord blood, and amniotic fluid obtained from 24 elective cesarean deliveries for both pro- and anti-inflammatory cytokines thought to be important in maintaining a balanced response leading to successful pregnancy outcome. These included interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-10, and IL-1 receptor antagonist (IL- 1ra). Amniotic fluid levels for each of the cytokines examined were significantly higher than those for cord blood or maternal plasma.”
Karacal, et al., have noted that human amniotic fluid may have a positive effect on bone healing in an experiment done with New Zealand white rabbits.
Ozganel, et al., noted a salutary effect of human amniotic fluid on nerve healing in rats. “Preliminary data showed that human amniotic fluid enhances peripheral nerve regeneration. The preventive effect of human amniotic fluid on epineural scarring and the rich content of neurotrophic and neurite-promoting factors possibly contribute to this result.”
Shimberg in 1938 reported on a series of 68 cases in which amniotic fluid was used in the treatment of patients with joint disease for various orthopedic conditions. His paper concluded the following:
  • In sixty-eight cases in which amniotic-fluid concentrate has been employed in the treatment of various pathological conditions of joints, the use of the fluid concentrate has not been attended by a single unfavorable reaction.
  • Its action is probably both biological and mechanical.
  • It speeds up a defense-repair mechanism within the joints.
  • The results obtained have been impressive in intra-articular fractures, and encouraging in selected cases of a trophic arthritis, as well as in persistent joint effusions.
  • It successfully prevents the formation of new adhesions after closed manipulation of joints.
  • It is a valuable prophylactic after arthrotomy of any type.
  • Its use both in soft tissues and in other serous cavities is suggested.
Demesmin, in unpublished research presented in an open forum in June, 2015, reviewed an “Interim Analysis of Prospective, Multi-Center Outcome Observational Cohort Registry of Amniotic Fluid Treatment for Osteoarthritis of the Knee.” With the caveats that this is an open label, non-randomized, uncontrolled trial, and that the full explanation for the N analyzed at the various time points was not presented, the data suggest a potential positive effect of AmnioVisc™, an allograft amniotic fluid viscosupplement, on osteoarthritis of the knee.
This effect was achieved with one dose, while the HA data compared were from a study in which 3-4 doses were given. VAS and WOMAC scores were measured in the study. The positive impact possibly persists out to 90 days. While this potential efficacy signal needs to be confirmed in a controlled trial, the results are encouraging.
Lastly, the safety profile as presented showed only 4 treatment-related adverse events (2.2%) were reported. This was noted as transient pain and tenderness which, in all cases, resolved within days with no treatment.