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Biomedical subjects

M Michejda

Publications and source records attributed to M Michejda.

At least 19 recordsLinked to original sources

Analysis and characterization of hematopoietic progenitor cells from fetal bone marrow, adult bone marrow, peripheral blood, and cord blood.

Hematopoietic stem cell transplantation has been increasingly used to replace a defective hematopoietic system and to treat various genetic defects as well as malignant diseases. However, the limitations of conventional bone marrow transplantation have stimulated an intense interest in exploring the use of alternative sources of hematopoietic stem cells, including peripheral blood mononuclear cells (PBMC) and cord blood (CB). A major investigative effort of our laboratory has been focused on evaluating fetal bone marrow (FBM) for transplantation. The current study compares and characterizes the functional and phenotypic characteristics of FBM, CB, adult bone marrow (ABM), and PBMC by clonogenicity assays, immunogenicity, and the quantification of progenitor cells. There was a striking difference in the proportion of CD34+ cells in FBM, ABM, PBMC, and CB (24.6%, 2.1%, 0.5%, and 2.0%, respectively). The clonogenic potential, as measured by colony forming unit in culture (CFU-C) assay, was significantly higher in FBM when compared with ABM, PBMC, and CB (202.5, 73.5, 40.8, and 65.5 colonies/10(5) cells, respectively). There was a significant decrease in proliferative responsiveness in mixed lymphocyte reaction (MLR) assay of FBM and CB compared with ABM and PBMC. These observations indicate that each source of hematopoietic stem cells has different intrinsic properties closely correlated with ontogenetic age that is a vital determinant for phenotypic characteristics, lineage commitments, immunogenicity, and proliferative potentials.

Adult↗

Quo vadis? Fetal tissue transplantation.

The epidemiology and biologic characteristics of fetal tissue harvested from elective and spontaneous abortions are reviewed. The use of fetal bone marrow obtained from second trimester lost pregnancies is discussed. Allogeneic fetal tissue transplantation carried out in utero is reviewed. Data on intrauterine transplantation of human fetal bone marrow obtained from second trimester lost pregnancies into baboon fetuses are presented. The viability of this tissue, its clonogenic efficiency, engraftment, use in the future, and banking are discussed.

Abortion, Induced↗

Fetal tissue from spontaneous abortions: a new alternative for transplantation research?

While transplantation of fetal tissues may alleviate a great deal of suffering, current policy bars federal funding of research using tissue from elective abortions. Using fetal tissue from spontaneous abortions would obviate the moral concerns. If existing studies of small samples are extrapolated to the US population, then each year about 750,000 fetuses are aborted spontaneously by week 28 (500,000 in the first trimester and 250,000 in the second trimester). The consensus among researchers is that spontaneously aborted fetuses are few in number, and inappropriate for transplantation because they are born dead or have defects. This intuition may not be supported by the evidence, and there is a compelling need to focus research on these issues.

Aborted Fetus↗

Allogeneic fetal bone cranioplasty in Macaca mulatta.

Teratogen-induced herniation of the occipital lobes (encephalocele) associated with cranium bifidum in monkey fetuses (Macaca mulatta) were repaired by amputation and cranioplasty in utero or postnatally. Fetal allogeneic cranial bone which had been fresh frozen was used in conjunction with a bone paste to provide a protective covering of the neural tissue following repair of the encephalocele. The bone graft in those animals treated in utero or 1-2 weeks post-partum developed a strong union with the calvarium, provided good protection for the underlying dura and neural tissue, had a smooth surface, and provided good cosmetic-reconstructive results. In contrast, when the cranioplasty procedure was performed on infant monkeys at 2-3 months of age the bone graft was rejected.

Age Factors↗

New animal model for the study of neural tube defects.

The induction of spina bifida in rhesus monkeys by treating the pregnant females with the anticonvulsant drug, valproic acid (VPA), during the early stage of gestation which coincides with the critical period of neural tube fusion is discussed. It was found that both the dosage and timing of VPA administration were crucial in the development of lesions which are similar to human spina bifida aperta. The teratogenic protocols and the gross and hystologic characterization of the induced lesions are presented and the epidemiological findings are discussed.

Animals↗

Present status of intrauterine treatment of hydrocephalus and its future.

At a time when the intrauterine diagnosis of hydrocephalus is common and pioneering efforts of antenatal therapy are evolving, an assessment of intrauterine treatment of this disorder becomes pertinent. Consequently, the current status of the intrauterine treatment of fetal hydrocephalus is presented. The new data from the International Fetal Surgery Registry at the University of Manitoba in Winnipeg are discussed. The technical problems of antenatal shunting, the clinical trials, and experimental treatment are assessed. The prognostication and possible new approaches in intrauterine treatment of hydrocephalus are presented as well as the new diagnostic and surgical techniques. The outcome of the antenatal diagnosis and treatment of fetal hydrocephalus is evaluated.

Animals↗

Intrauterine treatment of hydrocephalus.

The current status of the intrauterine treatment of fetal hydrocephalus is presented. The new data from the International Fetal Surgery Registry at the University of Manitoba in Winnipeg are discussed. Technical problems of antenatal shunting, clinical trials and experimental treatment are assessed. The outcome of the antenatal diagnosis and treatment of fetal hydrocephalus is evaluated.

Cerebrospinal Fluid Shunts↗

The fetal neural tube: is intervention progress?

Fetal therapy has now become a reality and many centres specializing in this field have been established in several countries. The in utero treatment of fetal hydrocephalus is bedevilled by many problems, including poor patient selection, problems with shunt design and general lack of understanding of the pathogenesis of hydrocephalus. Implantation of a ventriculo-amniotic shunt employing a one-way valve into the fetal skull allows continuous evacuation of CSF. One such model has been developed by us and should be ready for clinical trials in the near future. There is strong evidence that the fetal brain has a high capacity for rapid growth and regeneration. However, the process is poorly understood and there is great need for further study. No attempts have yet been made to treat spina bifida in utero. However, the advantages demonstrated in our earlier studies using allogeneic bone transplantation in utero resulted in the development of an allogenic bone paste. This substance can be moulded to any desired shape and is ideal for the restoration of bone loss resulting from cranial injuries or the correction of skull defects. The allogeneic bone paste has been also applied in utero for the repair of surgically induced spina bifida-like lesions in the animal model.

Animals↗