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At least 19 recordsLinked to original sources
PubMed2004

Fetal stem cells.

Fetal stem cells can be isolated from fetal blood and bone marrow as well as from other fetal tissues, including liver and kidney. Fetal blood is a rich source of haemopoietic stem cells (HSC), which proliferate more rapidly than those in cord blood or adult bone marrow. First trimester fetal blood also contains a population of non-haemopoietic mesenchymal stem cells (MSC), which support haemopoiesis and can differentiate along multiple lineages. In terms of eventual downstream application, both fetal HSC and MSC have advantages over their adult counterparts, including better intrinsic homing and engraftment, greater multipotentiality and lower immunogenicity. Fetal stem cells are less ethically contentious than embryonic stem cells and their differentiation potential appears greater than adult stem cells. Fetal stem cells represent powerful tools for exploring many aspects of cell biology and hold considerable promise as therapeutic tools for cell transplantation and ex vivo gene therapy.

Bone Marrow Cells↗
PubMed1993

Cryopreservation of fetal stem cells.

Fetal liver cells may be transplanted, in utero, to treat disorders affecting the hematopoietic system. Conventional immunological methods were employed to determine whether pooled cryopreserved cells could be a suitable basis for a tissue bank. We found that cryopreservation did not adversely change the population, viability or immunological capacity of human fetal liver cells and therefore, pooled and cryopreserved fetal stem cells may be suitable for transplantation.

Cryopreservation↗
PubMed2006

Fetal stem cells: betwixt and between.

Fetal stem cells can be isolated not only from fetal blood and hemopoietic organs in early pregnancy, but from a variety of somatic organs as well as amniotic fluid and placenta throughout gestation. Fetal blood is a rich source of hemopoietic stem cells, which proliferate more rapidly than those in cord blood or adult bone marrow. First-trimester fetal blood, liver, and bone marrow also contain a population of mesenchymal stem cells, which appear to be more primitive with greater multipotentiality than their adult counterparts. Fetal stem cells may thus represent an intermediate cell type in the current debate focusing on dichotomized adult versus embryonic stem cells, and thus prove advantageous as a source for downstream cell therapy applications. They have also been implicated in fetomaternal trafficking in pregnancy, and in long-term microchimerism in postreproductive women.

Female↗
PubMed1998

Current status in intrauterine fetal stem cell therapy.

In utero fetal stem cell transplantation, a today experimental treatment option, represents a new therapeutic strategy with broad implications for diseases related to the hematopoietic system. The object of the present paper is to give a review of the published literature on fetal stem cell therapy with special reference to immunological and strategical considerations. Furthermore, ethical considerations on account of the use of fetal cells are pointed out and a prospective view concerning experimental and clinical future perspectives is presented.

Fetus↗
PubMed1998

[The fetus as patient: intrauterine fetal stem cell transplantation].

In utero fetal stem cell transplantation, a still experimental treatment option, represents a new therapeutic strategy with broad implications for diseases related to the hematopoietic system. This survey reviews immunological and strategical considerations as well as previously published cases. Furthermore, ethical considerations on account of the use of fetal cells are discussed and a prospective view concerning experimental and clinical future perspectives is presented.

Female↗
PubMed1996

[Intrauterine fetal stem cell transplantation].

In utero fetal stem cell transplantation represents a new and still experimental therapeutic strategy for diseases related to the hematopoietic system. The broad therapeutic implications as well as potentials and limitations of this new technique are presented. To date, 6 cases of fetus-to-fetus transplantation have been published in the literature.

Female↗
PubMedDate not supplied

Screening of fetal stem cells for infection and cytogenetic abnormalities.

Fetal stem cell transplantation may rely on material from therapeutic abortions. It is essential that the stem cell transplant does not transmit any microorganisms that may affect the fetus and that genetically abnormal cells are avoided. To evaluate such contamination, human fetal stem cells collected February 1992 - December 1993 were analyzed for bacterial and fungal growth, and the placentas were karyotyped. Four samples of 70 were positive for different pathogens. Serological screening of 43 women during this period resulted in five seroconversions and revealed one carrier of anti-HCV. Karyotyping revealed two abnormal findings out of 72 samples. Thus, the concept of using material from therapeutic abortions is safe.

Abortion, Induced↗
PubMed1992

T cell repertoire and tolerance after fetal stem cell transplantation.

We studied the T cell repertoire and the mechanism of tolerance in two patients with severe combined immunodeficiency transplanted with HLA mismatched fetal liver stem cells. They are 17 and 5 years old now, healthy, and show normal immunoresponses to recall antigens. Their T cells are of donor origin, whereas monocytes and B cells remained of the host. The NK cells have different sources since in one patient they derive from the donor and in the other one from the host. Despite the HLA mismatch between donor and host cells, no acute or chronic graft-versus-host disease was observed. In vitro experiments with PBMC showed specific nonresponsiveness for the HLA antigens expressed by the host cells. However, an extensive clonal analysis showed that CD4+ and CD8+ host-reactive T cell clones recognizing class II and class I HLA molecules of the host, respectively, were present in the peripheral blood of both patients. Limiting dilution experiments indicated that the frequency of CD8+ host-reactive cells was in the same range as that observed for alloreactive T cells. In contrast, no donor reactive CD8+ T cells could be isolated. Host-reactive CD4+ and CD8+ T cell clones were normal in their capacity to produce IL-2, IFN-gamma, GM-CSF and IL-5, but they failed completely to synthesize IL-4. In addition, CD4+ T cell clones from patient RV secreted very high levels of IL-10. Interestingly, exogenous IL-10 was able to inhibit the proliferative responses of the CD4+ host-reactive T cell clones. Our data demonstrate that host-reactive cells are not deleted from the donor T cell repertoire following allogenic fetal liver stem cell transplantation. Therefore, in vivo tolerance between the host and the donor is maintained by a peripheral autoregulatory mechanism in which cytokines may play a role.

Adolescent↗
PubMed1996

Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies.

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.

Adult↗
PubMed1994

Establishment of a tissue bank for fetal stem cell transplantation.

STUDY OBJECTIVE: To analyse the yield of fetal liver tissue in first trimester abortions and to evaluate the number of nucleated cells obtained from each fetal liver during the sixth to twelfth week of gestation. DESIGN: Prospective descriptive study: LOCATION: University Hospital. MATERIAL: Women seeking abortion during a 12 month period 1992/1993. RESULTS: Out of 1271 women seeking abortion, 152 were asked whether they were willing to donate fetal tissue for fetal transplantation. Of these women, 105 (69%) accepted the proposal and underwent a modified low suction vacuum curettage. Fetal liver tissue was obtained in 61 (58%) of these procedures. The frequency at which tissue was retrieved was strongly related to gestational age and rose from 29% in week 6 to 79% in the tenth to twelfth week of gestation. The mean number of nucleated cells obtained from each fetal liver demonstrated a concomitant increase with gestational age, rising from 16 to 43 x 10(6) per liver during these weeks of gestation. Of the 61 cases in which fetal liver was obtained, four subjects were shown to be abnormal by laboratory analyses and 11 did not alter the mandatory follow-up appointment. This left 46 cases for use in the program of fetal to fetal transplantations. CONCLUSIONS: Most women seeking abortion seem to be in favor of the idea of fetal tissue donation for the treatment of other fetuses. The possibility of obtaining fetal liver tissue and the number of fetal stem cells retrieved are closely correlated to gestational age. A tissue bank appears to facilitate the operation of a fetal to fetal stem cell transplantation program.

Attitude to Health↗
PubMed2005

Stem cells for the treatment of liver disease.

Stem cells tantalise. They alone have the capacity to divide exponentially, recreate the stem cell compartment as well as create differentiated cells to build tissues. They should be the natural candidates to provide a renewable source of cells for transplantation. Does the reality support the promise of this exciting alternative to conventional therapies for metabolic and degenerative liver disease? Can techniques be developed to provide the large number of cells that could be required? Must there be "space" in the liver to accept the cells? To what extent is the liver immunoprivileged, and is immunosuppression necessary for stem cell therapy? Is it better to use haematopoietic stem cells, fetal stem cells, mesenchymal cells, embryonic stem cells, hepatocytes or all of the above, but for different disease indications? This paper discusses why the exploration of stem cells for the treatment of liver disease is of great potential, and delineates some of the hurdles that need to be overcome before patients see benefits from laboratory-based research into stem cell transplantation and function.

Animals↗
PubMed2000

Collection of fetal stem cells and newborn effects.

The aim of this work was to test fetal stem cells (FSC) number modification in relation to clamping time and newborn effect. The results show that a fast sample, between 20 and 40 seconds, from umbilical cord after fetus birth and before placental detachment assured a greater quantity of blood useful for the transplants; and that it was necessary to enrich the collected blood in CD34+ cells with specific clonogenic culture, as this is otherwise a small number for a donation to an adult. In the "new donors" the effects of the unconscious donation always depend on the clamping time, which should be the shortest possible to avoid blood overload, which is very dangerous in the presence of heart malformation.

Antigens, CD34↗
PubMed2003

[The revised Japanese pharmaceutical law and research ethics: risk-benefit assessment of fetal stem cell research].

The Japanese Pharmaceutical Law was revised at the end of July 2002. The important features of this revision are the postmarketing safety scheme, especially for biological products, and reconstruction of the legislation for effective pharmaceutical development. This is based on the national policy to foster life sciences such as genetic research and regenerative medicine for both healthcare improvement and industrial promotion. Such research requires study participants who donate human tissue including abandoned embryos or aborted fetuses, which may touch the human dignity. In particular, fetal stem cell research appears to have unpredictable risks not only to women who undergo abortions but also to societal epistemology. The authors conducted risk-benefit assessment of fetal stem cell research, reviewing the scientific, ethical, legal, and social aspects, including a case study of critical appraisal on a report of the double-blind, sham surgery-controlled trial of implantation of fetal tissues in patients with Parkinson's disease conducted in the USA. It is concluded that risk-benefit assessment with a wide, profound perspective is necessary for advanced biotechnology. Some types of research should not be assessed based only on such utilitarian viewpoints as risk and benefit. Conscientious reflection is necessary to reach a public consensus on which types of human material can be utilized as research or pharmaceutical resources.

Abortion, Induced↗
PubMed1992

SCID-hu mice as a model to study tolerance after fetal stem cell transplantation.

SCID-hu mice were constructed with human fetal liver and human fetal thymus, obtained from the same or from different donors. Hematopoietic cells originating from the fetal liver migrate to the fetal thymus and give rise to medullary and cortico-medullary macrophages and dendritic cells. Thymic epithelial cells remain of thymic donor origin. The fetal liver donor derived stem cells differentiate in this environment into double positive and finally single positive CD4 or CD8 expressing T cells. The TCR V beta repertoire generated at the double positive stage is identical to that generated in the thymus of the donor. Thymic selection induces changes in V beta usage comparable to those previously reported for normal human thymus. Single-positive, functionally mature, and mainly TCR alpha beta+ T cells reach the peripheral blood compartment of the SCID-hu mice. These T cells are able of specific proliferative and cytotoxic alloresponses. No autoreactivity is observed. Single positive T cells which differentiated in the thymus of SCID-hu mice transplanted with liver and thymus of two different donors are tolerant to the HLA antigens of both donors. By limiting dilution analysis, it could be demonstrated that tolerance to the fetal liver donor is due to clonal deletion whereas tolerance to the fetal thymus donor is not. These data show that human T cell development is progressing normally in these mice and gives rise to a mature, functional and polyclonal T cell repertoire which is comparable to that observed in normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

A new methodology of fetal stem cell isolation, purification, and expansion: preliminary results for noninvasive prenatal diagnosis.

We developed a combined methodological approach to enrich and to proliferate in vitro fetal CD34+ stem progenitor cells. Using a magnetic cell-sorting technique, CD34+ cells from pregnant women at the early-second trimester were isolated and enriched and compared to those isolated from blood of nonpregnant women. The number and frequency of CD34+ cells were significantly higher (p < 0.001) in the pregnant women. Unenriched peripheral blood mononuclear cells (PBMC) and enriched CD34+ cells were cultured in a methylcellulose system to evaluate the cloning potential of progenitor cells. After culture, the numbers of burst-forming units erythroid/colony-forming units erythroid (BFU-E/CFU-E) and colony-forming units granulocyte-macrophage (CFU-GM) colonies were increased by 33 and 16 times, respectively. Finally, to distinguish between fetal and maternal cells, four cases of cultured cells were hybridized with specific probes for X and Y chromosomes and two cases with a specific probe for chromosome 21. In normal pregnancies, we identified a high number of male fetal cells and an elevated fetal/maternal ratio. When we analyzed blood samples from pregnancies with trisomic fetuses, we scored a high ratio of trisomic cells respect to maternal cells that was significantly different from the ratio of pregnancies with normal fetuses. Our results demonstrate fetal progenitor cells may be cultured and detected successfully with an appropriate combined methodological approach, which may significantly increase the feasibility of noninvasive prenatal diagnosis.

Antigens, CD34↗
PubMed1983

Long-term erythropoietic repopulating ability of old, young, and fetal stem cells.

It is possible that erythropoietic stem cells do not age. This would mean that stem cells from old donors can function as well as those from young or fetal donors. The competitive repopulation assay has been used to test long-term stem cell function by directly comparing how well competing stem cells repopulate a recipient and produce differentiated cell types. C57BL/6J (B6) mice were used as donors, while recipients and competitors were WBB6F1 hybrids with genetically distinguishable hemoglobin. Lethally irradiated young WBB6F1 recipients were given a mixture of 2.5 X 10(6) cells from B6 old marrow, young marrow, or fetal liver donors; each recipient also received a standard dose of 1 X 10(6) marrow cells from a pool of young WBB6F1 competitors. Surprisingly, the old marrow cells competed the best in repopulating the recipients. This pattern was maintained even after recovery from sublethal irradiation, a treatment that severely stresses stem cells. This stress was demonstrated when sublethal irradiation caused a 20-fold decline in repopulating ability measured using hemoglobin markers, and a 3- to 7-fold decline using chromosome markers. Stem cells from old marrow competed better than young or fetal cells in similar experiments using immunologically crippled recipients or using unirradiated W/Wv recipients that are immunologically intact. In both types of recipients, the advantage of old marrow cells again persisted after recovery from sublethal irradiation. Other genotypes were tested, and marrow cells from old B6CBAF1 donors competed better than those from young donors of that genotype. However, marrow cells from young CBA donors completed better than those from old CBA donors. These results support the hypothesis that stem cells do not age, and suggest that regulatory changes with age promote rapid stem cell repopulation in B6 and B6CBAF1 mice, but inhibit it in CBA mice.

Aging↗
PubMed2004

Isolation of murine and porcine fetal stem cells from somatic tissue.

Adult stem cells have been previously isolated from a variety of somatic tissues, including bone marrow and the central nervous system; however, contribution of these cells to the germ line has not been shown. Here we demonstrate that fetal somatic explants contain a subpopulation of somatic stem cells (FSSCs), which can be induced to display features of lineage-uncommitted stem cells. After injection into blastocysts, these cells give rise to a variety of cell types in the resultant chimeric fetuses, including those of the mesodermal lineage; they even migrate into the genital ridge. In vitro, FSSCs exhibit characteristics of embryonic stem cells, including extended self-renewal; expression of stem cell marker genes, such as Pou5f1 (Oct4), Stat3, and Akp2 (Tnap) and growth as multicellular aggregates. We report that fetal tissue contains somatic stem cells with greater potency than previously thought, which might form a new source of stem cells useful in somatic nuclear transfer and cell therapy.

Animals↗