Human fetal tissues grafted to rodent hosts: structural and functional observations of brain, adrenal and heart tissues in oculo

Abstract

The potential for growth and development of human tissue grafts was explored by transplantation to the anterior chamber of the eye of rats and mice. Tissues were obtained from therapeutic abortions, performed in the eighth to twelfth week of gestation, using a slight modification of routine vacuum aspirations. Recipients were either adult rats immunosuppressed with cyclosporin A and protected with antibiotics, or nude immunodeficient Balb C mice. Catecholamine-rich tissues such as chromaffin cells from the adrenal medulla, sympathetic ganglia, central dopamine neuroblasts from the substantia nigra, and noradrenaline neuroblasts from the locus coeruleus all survived grafting, and in many cases formed nerve fibers that invaded the host iris. Similarly, central serotonin neurons from developing raphe nuclei grafts were able to innervate host irides. Human fetal cerebellar and cerebral cortical transplants continued their development in rat host eyes. Extracellular recordings from such cerebellar and cortical grafts revealed spontaneously active cells with immature action potential waveforms. Spinal cord grafts also survived and contained substance P-immunoreactive neurons. Dorsal root ganglia were able to form nerve fibers invading the host iris, as evidenced by neurofilament immunohistochemistry. Heart tissue survived and manifested spontaneous rhythmic contractions in oculo. Both human cortex cerebri and heart tissue grafts became innervated by sympathetic adrenergic nerve fibers from the rat host iris. Thus both graft-to-host and host-to-graft neuronal connections may be established between man and rat. Taken together, these data suggest that transplantation of human fetal nervous tissues to the anterior chamber of immunosuppressed or immunodeficient rodent hosts yields a unique model system for studies of human brain development, developmental disturbances, connectivity, and the action of drugs.