Fetal Tissue from Spontaneous Abortions: A New Alternative for Transplantation Research?

Due to immunological immaturity, the fetus is the ideal recipient as well as donor of haemopoietic stem cells (HSCs); thus intrauterine therapy may prove to be effective in all major haemopoietic disorders when early prenatal diagnosis is available. In man, ‘fetus-to-fetus’ transplantation has demonstrated the possibility of grafting donor HSCs and reconstituting immunodeficient fetuses. The limitations of fetal tissue use for transplantation derive from the origin of tissues from elective abortions. Early and late live spontaneous abortions may constitute an alternative to elective abortions, but are widely considered as unsuitable for fetal tissue collection because of rapid loss of viability and/or infections. The aim of this retrospective study was to assess the number of live abortions in a population of women who underwent spontaneous abortion in a single centre. In a 19-month period, 9 spontaneous abortions alive at the moment of delivery and 8 with a heart beat at the last ultrasound scan before abortion were recorded. In 1 case, fetal liver (FL) harvesting was easily performed and the tissue was cryopreserved, subsequently thawed and injected into a monkey fetus. This case shows the feasibility of this approach. The majority of cases reviewed consisted of late abortions. These findings clearly show that fetal tissue collection from spontaneous abortions is feasible for research purposes, for postnatal FL transplantation and for intrauterine transplantation, provided that depletion of more mature cells is performed when FL of later gestational age are used. The number of fetuses collected could be further augmented provided that a multicentre network for fetal tissue collection is established.

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fetal Tissue Collection from Spontaneous Abortions: A Report from a Single Centre

Tocci¹,

Menichella

Perretta

et al. 1994

“…Over 10 years ago we carried an epidemiological study on the incidence of spontaneous miscarriages [47]. This work provided important data to show that the number of miscarriages that could provide viable second trimester fetal tissue was very large.…”

Section: Comparative Study Of Stem Cells Derived From Various Sourcesmentioning

confidence: 99%

Which Stem Cells Should be Used for Transplantation?

Michejda¹

2003

Self Cite

In view of the ever-increasing demand for human stem cells for transplantation, we initiated in vitro and in vivo studies of human fetal bone marrow stem/progenitor cells derived from lost pregnancies at 16–20 weeks. Utilizing non-human primates as models, we demonstrated that fetal tissue has distinctive biological and therapeutic properties that are optimal for transplantation. Subsequently, we tested and compared the phenotypic and functional characteristics of fetal bone marrow (FBM), adult bone marrow (ABM), and cord blood (CB) and peripheral blood (PB) sources of the most primitive stem/progenitor cells. A striking ontogenic difference in the proportion of CD34+ cells in FBM, ABM, PB and CB was observed (24.6 vs. 2.1 vs. 0.5 vs. 2%). The clonogenic potential, as measured by the CFU-c assay, was also higher in FBM when compared with ABM, PB and CB (202.5 vs. 73.5 vs. 40.8 vs. 65.5 colonies/10⁵cells). Moreover, there was a significant decrease in proliferative responsiveness in the mixed lymphocyte reaction (MLR) assay of FBM and CB as compared to ABM and PB. The cytokinetic profiles of the cells from the four sources were also analyzed. This study revealed that both FBM and ABM had a higher proportion of S-phase (21.7 and 11.5%, respectively), compared to PB and CB cells (1.2 and 2.8%, respectively). FBM and ABM also showed a higher proportion of cells in the G₂-M phase (6.4 and 2.6%, respectively) compared with PB and CB (1.7 and 1.2%, respectively). These data show that FBM has the highest number of proliferating cells. We have also investigated the ontogenic differences in stromal cells derived from FBM, ABM and CB, with a special focus on the expression of selected cytokines, such as CSF, GM-CSF, G-CSF, M-CSF, IL-3, IL-6, IL-10 and IL-11. FBM showed the highest levels of expression of CSF, IL-6 and IL-11 when compared to the other sources. These cytokines may have an important role in engraftment and homing of stem cells. The levels of expression of the other cytokines were similar in all sources of stromal cells, with the exception of G-CSF, which was not detected in CB. Moreover, the number of colonies FBM and ABM cells was higher when inoculated with fetal stromal cells. These results suggested an important regulatory role of cytokines in ontogeny of hematopoiesis. In summary, the foregoing observations indicate that each source of hematopoietic and stromal cells has different intrinsic properties, closely correlated with ontogenetic age, which is a vital determinant for phenotypic characteristics, lineage commitments, immunogenicity as well as proliferative potentials. Our data clearly indicate that FBM is the best source of stem cells for engraftment and therapeutic reconstitution due to its very high proliferative capacity, low immunogenicity and highest number of primitive stem/progenitor cells. It should also be stressed that FBM stem cells retrieved at their optimal stage of hematopoiesis (16–20 weeks) may be the cells of choice for both therapeutic cellular reconstitution...

“…Also, another option is to secure fetal tis sue from spontaneous abortions, as dis cussed by Thorne and Michejda [22], They showed that the number of such events that occur in hospitals in the United States (pos sibly 750,000) are large enough to justify organized preparedness to use these tissues instead of those from elective abortions.…”

Section: Two Options For Actionmentioning

confidence: 99%

Fetal Tissue Transplantation Research and Federal Policy: A Growing Wall of Separation

Fletcher

1990

The federal moratorium on fetal tissue transplantation research is creating an ever growing wall of separation between public and private research. This federal policy is based on undocumented psychological assumptions about what motivates women to have abortions, neglects to consider the suffering that could be prevented by allowing such research, disregards the fact that other forms of fetal research are performed at federal expense, infringes on the scientific freedom of federally employed scientists and compromises the federal government’s ability to control the quality of research. Efforts must be made to legally dismantle this wall before it further impedes the goals of medical research.