Amniotic fluid and placental stem cells

doi:10.1016/j.bpobgyn.2004.07.001

Best Practice & Research Clinical Obstetrics & Gynaecology

Volume 18, Issue 6, December 2004, Pages 877-891

https://doi.org/10.1016/j.bpobgyn.2004.07.001 Get rights and content

The amniotic fluid and the placenta are unique sources of different populations of stem cells—mesenchymal, hematopoietic, trophoblastic—and, possibly, of more primitive stem cells. Although much of the amniotic cavity/fluid and the placenta share a common embryonic origin, the specific origins of the stem cells found in these two compartments remain to be determined. Accordingly, it is not yet known whether all or part of these two stem-cell subsets are actually the same. The multilineage potential of the different stem cell populations from these two sources has begun to be described but still much remains to be learned. Thus, it is not surprising that clinical applications related to the use of these cells have yet to be reported. Nevertheless, fertile experimental work from many different groups has introduced a number of promising novel therapeutic concepts utilizing these cells, such as in tissue engineering, cell transplantation, and gene therapy.

Section snippets

Amniotic fluid

Embryonic and fetal cells from all three germ layers have long been identified in the amniotic fluid.2., 3., 4., 5. However, the specific origins of many subsets of these cell types still remain to be determined. The profile of the cellular component of the amniotic fluid varies with gestational age.6., 7. In addition to the common origin with the mesenchymal portion of the placenta, as mentioned above, throughout pregnancy the amniotic cavity/fluid receives cells shed from the fetus and, quite

Placenta

The cell types found in the placenta at different gestational ages are a result of the mechanisms behind placental development. In the human placenta, villous development starts between 12 and 18 days post-conception (p.c.), when the trophoblastic trabeculae of the placental anlage proliferate and form trophoblastic protrusions, the primary villi, into the maternal blood surrounding the trabeculae.⁴¹ Two days later, embryonic connective tissue from the extra-embryonic mesenchyme invades these

Ethical considerations

The cells present in the amniotic fluid and in most of the placenta are fetal cells. The use of fetal tissue/cells has always been object of intense ethical debate. The main reason for the current ethical controversies comes from the fact that the primary source of fetal tissue is induced abortion. Spontaneous abortion does not usually raise many moral issues. The National Institutes of Health, the American Obstetrical and Gynecological Society and the American Fertility Society, in accordance

Perspectives of clinical applications

Because the proposition that stem cells can be isolated from the amniotic fluid and the placenta, then expanded and manipulated in culture, is so recent, it is not surprising that a therapeutic application of these cells has yet to be reported in humans. Nevertheless, different uses of these cells have already been demonstrated experimentally in animal models.

One example is the concept of utilizing the amniotic fluid or the placenta as stem cell sources for fetal tissue engineering (Figure 2).

Summary

The amniotic fluid and the placenta might provide the least invasive access to different stem cell populations, including mesenchymal and—possibly—embryonic stem cells. Mesenchymal stem cells are by far the more abundant and easy to isolate. What could be embryonic-like stem cells, however, cannot always be isolated with current methods and represent less than 1% of the cells present in amniotic fluid or placental samples. To date, mesenchymal amniocytes have shown multilineage potential into

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Cited by (228)

Bidirectional Feto-Maternal Traffic of Donor Mesenchymal Stem Cells Following Transamniotic Stem Cell Therapy (TRASCET)
2024, Journal of Pediatric Surgery
Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has emerged experimentally as a potential treatment for different congenital diseases and maternal diseases of pregnancy. The broad applicability of TRASCET is predicated on hematogenous routing of donor MSCs via the placenta. We investigated whether donor MSC kinetics includes bidirectional traffic between the fetus and mother.
Eight time-dated dams had their fetuses (n = 96) divided in 4 groups on gestational day 17 (E17, term = E21). Groups populating one uterine horn received intra-amniotic injections (50 μL) of either donor amniotic fluid-derived MSCs (2×10⁶ cells/mL) labelled with a firefly luciferase reporter gene (MSC-injected, n = 32), or of acellular luciferase (luciferase-injected, n = 26). Contra-lateral (CL) horn fetuses received no injection (MSC-CL, n = 20 and luciferase-CL, n = 18). At term, samples from 11 fetal anatomical sites from CL fetuses, along with placentas from all fetuses and maternal blood were screened for luciferase activity via microplate luminometry.
Overall survival was 95 % (91/96). When controlled by the acellular injection, positive luciferase activity was observed in the placentas of all MSC-injected fetuses, confirming viability of the donor cells at term. When controlled by the acellular injection group, MSC-CL fetuses showed positive luciferase activity in the bone marrow, peripheral blood, brain and skin (p = <0.001–0.048). No luciferase activity was detected in any maternal blood sample.
Amniotic fluid-derived MSCs can traffic between the fetus and mother in both directions after simple intra-amniotic injection, in a healthy rat model. This phenomenon must be considered in TRASCET performed in twin/multiple pregnancies.
N/A (animal and laboratory study).
Transamniotic stem cell therapy (TRASCET): An emerging minimally invasive strategy for intrauterine stem cell delivery
2023, Seminars in Perinatology
Transamniotic stem cell therapy (TRASCET) is an emerging strategy for prenatal stem cell therapy involving the least invasive method described to date of delivering select stem cells to virtually any anatomical site in the fetus, including the blood and bone marrow, as well as to fetal annexes, including the placenta. Such broad therapeutic potential derives, to a large extent, from unique routing patterns following stem cell delivery into the amniotic fluid, which have commonalities with naturally occurring fetal cell kinetics. First reported experimentally only less than a decade ago, TRASCET has yet to be attempted clinically, though a first clinical trial appears imminent. Despite significant experimental advances, much promise and perhaps excessive publicity, most cell-based therapies have yet to deliver meaningful large-scale impact to patient care. The few exceptions typically consist of therapies based on the amplification of the normal biological role played by the given cells in their natural environment. Therein lays much of the appeal of TRASCET, in that it, too, is in essence a magnification of naturally occurring processes in the distinctive environment of the maternal-fetal unit. As much as fetal stem cells possess unique characteristics compared with other stem cells, so does the fetus when compared with any other age group, converging into a scenario that enables therapeutic paradigms exclusive to prenatal life. This review summarizes the diversity of applications and biological responses associated with the TRASCET principle.
Transamniotic stem cell therapy (TRASCET) for intrauterine growth restriction (IUGR): A comparison between placental and amniotic fluid donor mesenchymal stem cells
2023, Journal of Pediatric Surgery
Citation Excerpt :
Both the amniotic fluid and the placenta can serve as relatively easily accessible sources of fetal MSCs. The amniotic fluid-derived afMSCs are known to be anti-inflammatory and could possibly modulate uNK cell associated inflammatory signaling in IUGR [7–9]. Placenta-derived MSCs (pMSCs) could possibly contribute to regulating angiogenesis, thus improving IUGR-associated spiral artery remodeling and placental dysfunction [10–11].
Transamniotic stem cell therapy (TRASCET) with donor mesenchymal stem cells (MSCs) has been shown experimentally to reverse central effects of intrauterine growth restriction (IUGR). We sought to compare amniotic-fluid and placenta-derived MSCs (afMSCs and pMSCs, respectively) as TRASCET donor cells in a murine IUGR model.
Pregnant Sprague-Dawley dams (n=8) were exposed to alternating 12-hour hypoxia (10.5% O₂) cycles, starting on gestational day 15 (E15; term=E21-22). On E17, fetuses (n=100) were divided into four groups. An untreated group had no further manipulations (n=24). Three groups received volume-matched intra-amniotic injections of either saline (sham; n=27), or suspensions of afMSCs (n=24), or pMSCs (n=25). Normal fetuses served as controls (n=21). All infused MSCs consisted of syngeneic Lewis rat cells phenotyped by flow cytometry and GFP-labeled. At term, fetal and placental morphometrics were calculated, and placental TNF-α levels were determined by ELISA. Statistical comparisons were by Fischer's T-test or Wilcoxon rank sum test (p≤0.05).
Overall survival of the hypoxic groups was 83% (83/100). Compared to normal, maternal-adjusted fetal weights were significantly decreased in all hypoxia groups (pairwise p<0.001), however only the afMSC group showed higher adjusted-fetal weights than sham (p<0.001). Placental efficiency was decreased in untreated, sham, and pMSC groups (p<0.001-0.056) but normalized in the afMSC group (p=0.205). Maternal-adjusted placental weights were lower than normal in all hypoxia groups (p<0.001-0.045), except for the pMSC group (p=0.387).
Amniotic fluid-derived mesenchymal stem cells are superior to their placenta-derived counterparts in transamniotic stem cell therapy for intrauterine growth restriction in a rat model.
Basic/Translational science.
Routing pathway of syngeneic donor hematopoietic stem cells after simple intra-amniotic delivery
2022, Journal of Pediatric Surgery
We sought to determine the pathway through which syngeneic hematopoietic stem cells (HSCs) delivered into the amniotic fluid can reach the fetal circulation.
Lewis rat fetuses were divided in two groups based on the content of intra-amniotic injections performed on gestational day 17 (E17; term=E21–22): either a suspension of luciferase-labeled syngeneic HSCs (n = 137), or acellular luciferase (n = 44). Samples from placenta, chorion, amnion, amniotic fluid, umbilical cord, and 8 fetal sites were procured at 5 daily time points thereafter until term for analysis.
When controlled by acellular luciferase, donor HSCs were identified in the amnion, chorion, placenta, and amniotic fluid of fetuses receiving cells at all time points (p = 0.033 to <0.001), peaking first at the amnion and subsequently at the chorion and placenta. Cells could be detected in the fetal liver as early as day 1, progressively expanding to all the other fetal sites over time, in parallel to their increased presence in the chorion and placenta.
The chronology of syngeneic donor hematopoietic stem cell trafficking after intra-amniotic injection is suggestive of controlled routing through the gestational membranes and placenta. Hematogenous donor cell routing is a constituent of transamniotic hematopoietic stem cell therapy, significantly expanding its potential applications.
Intrauterine Growth Restriction (IUGR) as a potential target for transamniotic stem cell therapy
2022, Journal of Pediatric Surgery
Citation Excerpt :
These cells are naturally present in the placenta and have a number of biological roles there, many of which are unrelated to inflammation [25,26]. Indeed, the placenta is known to have a sizeable mesenchymal progenitor cell component [26]. Its role in placental development involves, at least in part, the recruitment of its cells to support the vigorous angiogenesis that occurs during vascularization of the villous sprouts, in addition to the angiogenesis based on the proliferation of endothelial precursors [27].
We sought to determine whether intrauterine growth restriction (IUGR) could be a target for mesenchymal stem cell (MSC)-based transamniotic stem cell therapy (TRASCET).
Pregnant dams subjected to hypoxia (10.5% O₂) cycles had their fetuses divided into four groups: untreated (n = 24) and three groups receiving volume-matched intra-amniotic injections of either saline (sham; n = 16), or suspensions of luciferase-labeled, syngeneic amniotic fluid-derived MSCs that were either native (TRASCET-unprimed; n = 29), or primed by exposure to IFNγ and IL-1β (TRASCET-primed; n = 31). Normal fetuses served as additional controls (n = 22). Multiple analyses were performed at term.
Compared to normal, fetal weights were significantly decreased in all hypoxia groups (p = 0.002 to <0.001), except for TRASCET-primed. Placental efficiency (fetal/placental weight) was significantly decreased in all hypoxia groups (p = 0.002 to <0.001), but normalized in both TRASCET groups. A significant increase in metrial expression of IFNγ in both the untreated and sham groups (p = 0.04 to 0.02) was reversed only in the TRASCET-primed group. Luciferase DNA was present in both TRASCET groups’ placentas.
Transamniotic stem cell therapy with primed mesenchymal stem cells reverses some of the effects of intrauterine growth restriction in a rat model. Further study into this novel approach for the treatment of this disease is warranted.
N/A (Animal and Laboratory Study)
Unselected CD117 expression in amniotic and placental mesenchymal stem cells
2021, Journal of Pediatric Surgery

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4Amniotic fluid and placental stem cells

Section snippets

Amniotic fluid

Placenta

Ethical considerations

Perspectives of clinical applications

Summary

Methods in Cell Biology

Blood

Neuroscience Letters

Neuroscience

Blood

Journal of Pediatric Surgery

Journal of the American College of Surgeons

Experimental Hematology

Cell

Mutation Research

Placenta

Placenta

Cell Transplantation

Journal of Pediatric Surgery

Placenta

Placenta

Placenta

Journal of Pediatric Surgery

Journal of Pediatric Surgery

Journal of Pediatric Surgery

An embryogenic model to explain cytogenetic inconsistencies observed in chorionic villus versus fetal tissue

Prenatal Diagnosis

Amniotic fluid cell culture

Amniotic fluid cell types and culture

British Medical Bulletin

Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research?

Human Reproduction

Identification of hematopoietic progenitor cells in human amniotic fluid before the 12th week of gestation

Italian Journal of Anatomy and Embryology

Prenatal diagnosis of common aneuploidies using quantitative fluorescent PCR

Prenatal Diagnosis

Dynamics and disorders of amniotic fluid

Ion fluxes across the pulmonary epithelium and the secretion of lung liquid in the foetal lamb

Journal of Physiology

Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb

Journal of Applied Physiology

Amniotic fluid digestive enzymes: diagnostic value in fetal gastrointestinal obstructions

Prenatal Diagnosis

Protein analysis in amniotic fluid and fetal urine for the assessment of fetal renal function and dysfunction

Fetal Therapy

Human and ovine amniotic fluid composition differences: implications for fluid dynamics

Journal of Maternal Fetal Medicine

The biochemistry of amniotic fluid

In vitro transformation of amniotic cells to muscle cells-background and outlook

Wiener Medizinische Wochenschrift

Collagen synthesis in long-term amniotic fluid cell cultures

Nature

Biochemical characteristics of collagen produced by long term cultivated amniotic fluid cells

Human Genetics

4
Amniotic fluid and placental stem cells