Are Amniotic Fluid Products Stem Cell Therapies? A Study of Amniotic Fluid Preparations for Mesenchymal Stem Cells With Bone Marrow Comparison

Panero, Alberto; Hirahara, Alan M.; Andersen, Wyatt J.; Rothenberg, Joshua; Fierro, Fernando A.

doi:10.1177/0363546519829034

Cited by 29 publications

(21 citation statements)

References 29 publications

(50 reference statements)

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“…Since these cells have not been culture expanded, they do not meet the ISCT criteria for an MSC population and should not be referred to as “mesenchymal stem cells.” A recent independent analysis of 3 commercially available amniotic fluid products found that none formed any CFUs in culture, confirming the absence of any MSCs in these products. 11 Most of the commercially available cell formulations derived from placental and amniotic tissues are poorly characterized and currently lack rigorous analysis of the cell content and biologic activity. These materials are often marketed as “stem cell” preparations, which they clearly are not.…”

Section: Placenta Umbilical Cord Blood and Amniotic Tissuesmentioning

confidence: 99%

Stem Cells 101

Rodeo¹

2021

Am J Sports Med

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In a recent issue of The American Journal of Sports Medicine, Ruoss and coauthors 13 characterized mesenchymal stromal cells (MSCs) in human bone marrow aspirate concentrate at the single-cell transcriptome level. They reported that currently available methods lack consensus at the single-cell transcriptome and protein expression levels, demonstrating the challenges in quantifying the presence, biologic activity, and heterogeneity of MSCs. The journal receives a large number of submissions presenting the results of studies of cell therapy for a number of sports medicine issues. These cell therapy studies include a large diversity of cell types, including cells derived from bone marrow, adipose tissue, placenta, umbilical cord blood, and amnion, with cell sources ranging from autogenic to allogenic and even xenogenic. Furthermore, there is wide diversity in the techniques used for harvesting and processing the cells, with some being culture expanded, digested using enzymes, microfragmented using mechanical dissociation, or even transfected with a specific gene. It goes without saying that there is tremendous heterogeneity in the final composition and biologic activity of these cell formulations, many of which are lumped together as ''stem cells.''As the field of orthobiologics continues to expand, cellbased therapies will play a central role. After all, no amount of growth factors, cytokines, signaling molecules, or high-tech tissue engineered scaffold can support new tissue formation without cells. To accurately report studies and move the field forward, accurate nomenclature is critical. To that end, in this editorial I try to provide some clarity to help investigators report their studies and readers who study this material.The term ''stem cell'' is perhaps one of the most overused terms in the orthopaedic literature. Caplan 1 introduced the term ''mesenchymal stem cells'' to the orthopaedic vernacular in a classic 1991 article. The term conjures up images of cells that can support the formation of a variety of new tissues after transplantation. However, true tissue formation in vivo using culture-expanded cells has proven to be elusive. The term ''stem cells'' has been widely misused in aggressive advertising and marketing, implying promise that has largely not been demonstrated in preclinical and clinical studies. At the same time, positive effects of cell transplantation are certainly known to occur, even without long-term engraftment or survival of transplanted cells.

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Section: Placenta Umbilical Cord Blood and Amniotic Tissuesmentioning

confidence: 99%

Stem Cells 101

Rodeo¹

2021

Am J Sports Med

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“…Mid-trimester and term human amniotic fluid stem cells (hAFSCs) are available in large quantities and have been well characterized as multipotent cells that can be a resource for clinical transplantation and allow their future therapeutic use as an ''off-the-shelf'' cell source in regenerative medicine. 8,9 hAFSCs collected during pregnancy were demonstrated to have remarkable plasticity, and immunomodulatory effects and have the potential for the treatment of various diseases especially in neonates when autologous cell therapy is required; even immediately after birth. 5,9 They also have a pluripotent potential property identical to embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) that can be reprogrammed to a pluripotency potential without any genetic manipulation.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Age and Type of Media on Growth Kinetics of Human Amniotic Fluid Stem Cells

Borzou

Mehrabani

Zare

et al. 2020

Biopreservation and Biobanking

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This study compared growth kinetics of human amniotic fluid stem cells (hAFSCs) in different maternal age groups and two different media of AmnioMAX and Dulbecco's modified Eagle's medium (DMEM). Materials and Methods: Three milliliters of amniotic fluid (AF) was provided from 16 pregnant women who were referred for amniocentesis from 16 to 18 weeks of gestation. Mothers were divided to 20-29 (n = 5), 30-39 (n = 5) and 40-49 (n = 6) years old age groups. AF was immediately centrifuged and the cell pellet was cultured. Cells were characterized morphologically, by flow cytometry and for osteogenic and adipogenic inductions. Population doubling time (PDT) and growth kinetics were determined. AFSCs cultured in AmnioMAX were compared in various age groups. A comparison of growth kinetics of AFSCs cultured in AmnioMAX and DMEM from 40 to 49 years old pregnant women was undertaken. Results: AFSCs were adherent to culture flasks and were spindle shape, and positive for osteogenic and adipogenic inductions and for expression of CD73, CD90 and CD105 markers, but negative for CD34 and CD45. PDT among 20-29, 30-39, and 40-49 years old women was 30.9, 38.3, and 43.9 hours, respectively showing a higher cell proliferation in younger ages. When comparing AmnioMAX and DMEM, PDT was 53 and 96.9 hours, respectively denoting to a higher cell proliferation in AmnioMAX. Conclusions: Higher proliferation and plasticity of hAFSCs were noted in AmnioMAX and in younger mothers' samples. These findings can be added to the literature and open a new avenue in regenerative medicine, when hAFSCs are targeted for cell therapy purposes.

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“…A recent, elegant study evaluated stem cells in amniotic fluid products and also showed that no live stem cells were identified in 3 tested products. 22 It is common that 1 or a limited number of cell surface/CD markers are used to identify MSCs in a product. A critical concept is that there is no single CD marker that will identify MSCs; a panel of markers, used simultaneously, is required to positively identify stem cells.…”

Section: Discussionmentioning

confidence: 99%

Amnion and Umbilical Cord–Derived Products in Sports Medicine: From Basic Science to Clinical Application

et al. 2021

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Background: Birth tissue products from amnion, chorion, umbilical cord, amniotic fluid, or cord blood are frequently marketed as viable sources of stem cells and growth factors. It can be difficult for health care professionals to differentiate implied from explicit conclusions in reported product analyses. Purpose: To provide an educational platform for health care professionals to interpret data presented in the promotion of birth tissue products. Study Design: Descriptive laboratory study and expert opinion; Level of evidence, 5. Methods: A cord blood product was analyzed by 3 methods for cell viability, 2 methods for assessment of cell morphology and cell type, multicolor flow cytometry to identify stem cells, and enzyme-linked immunosorbent assay (ELISA) plus Western blot for analysis of interleukin 1 receptor antagonist protein (IL-1ra). These data were compared with analyses reported by the manufacturer. Results: Cell viability in the cord blood product was less than reported by the manufacturer, the cells were primarily leukocytes, no stem cells were present, and the concentration of IL-1ra was falsely increased due to nonspecific antibody binding in the sample. Conclusion: To assess birth tissue products, health care professionals should consider the following: (1) Understanding fluorescent dyes is important for assessing cell viability data—green does not always mean alive. (2) The report of “cells” in the product does not necessarily mean “stem cells”; microscopic images of at least ×20 or a hemogram should be evaluated to determine cell type (leukocyte, red blood cells, etc). (3) There is no single cluster of differentiation (CD) marker on flow cytometry to identify stem cells. (4) Biological tissues are complex substances, and inaccurately increased measurements of growth factors could be present in ELISA results because most ELISAs are not designed or validated for use in biologics. Furthermore, the reported measurement of growth factors should be considered relative to concentrations in native biological tissues and plasma. Clinical Relevance: Health care professionals should be able to interpret cell viability, cell morphology, stem cell analysis using CD markers, and growth factor analysis when considering use of a birth tissue product in patients.

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Are Amniotic Fluid Products Stem Cell Therapies? A Study of Amniotic Fluid Preparations for Mesenchymal Stem Cells With Bone Marrow Comparison

Cited by 29 publications

References 29 publications

Stem Cells 101

Stem Cells 101

The Effect of Age and Type of Media on Growth Kinetics of Human Amniotic Fluid Stem Cells

Amnion and Umbilical Cord–Derived Products in Sports Medicine: From Basic Science to Clinical Application

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