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Fetal Treatment Laboratory Research
Fetal Stem Cell Transplantation
A variety of studies are ongoing, all directed towards improving the clinical uses of hematopoietic stem cells, both fetal and adult, for in-utero fetal transplantation as well as ex vivo progenitor expansion and gene therapy. Our laboratory has demonstrated that both adult and fetal stem cells can be transplanted into a pre-immune fetus (less than 15 weeks gestational age) producing long-lasting engraftment without graft-versus-host disease, without rejection, or the need for immunosuppression.
Studies are underway to develop methods to increase the level of chimerism in these fetal recipients as well as the development of tolerance to donor tissue such that postnatal solid organ transplantation could be performed without the need for long-term immunosuppression. The overall strategy can also be used to treat fetuses with detectable inherited diseases such as hemoglobinopathies, immunologic deficiencies and enzyme deficiencies, all of which can be diagnosed early enough in pregnancy to allow fetal transplantation. Related studies involve understanding the mechanisms which regulate fetal and adult hematopoiesis, specifically the environmental signals such as growth factors and cell surface molecules. All studies are performed in rodent, sheep and monkey animal models.
Myometrial-Targeted Liposomal Tocolysis
The effectiveness of current tocolytic therapies following open fetal surgery and in the general obstetrical practice is greatly reduced by the pronounced systemic side effects and fleeting tocolytic action. We will attempt to overcome these disadvantages by designing tocolytic agents with reduced systemic side effects, targeted to the myometrium, and with prolonged duration of action through formulation of tocolytic drugs within a recently introduced drug carrier, long-circulating liposomes.
Long-circulating liposomes have already proved useful for increasing specificity of drug delivery and reducing systemic side effects of cytotoxic drugs in the chemotherapy of solid tumors. Within this project, tocolytic agents will be encapsulated into long-circulating liposomes. Site-specific effect and retention of long-circulating liposomes in myometrial tissue will be achieved by coating them with synthetic peptides having high affinity to the human uterine oxytocin receptor; while the prolonged action of liposome-encapsulated tocolytic agent will be achieved by its sustained release through the liposome membrane.
Development of Tissue Engineering
This research will assist in the care of children, infants, and unborn patients with diseases, in particular, investigation of signaling mechanisms for improving engraftment of hepatocytes on biodegradable polymer three-dimensional polymer matrices. This background will then be used to investigate liver regeneration as well as developing therapies for liver replacement of the pediatric and fetal population.
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