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Neural tissue transplant represents one of the most exciting and controversial areas of current basic neuroscience research. It offers enormous therapeutic promise for patients with degenerative and traumatic neurologic disorders. This article reviews the functions of several common neurotransmitters and examines the clinical applications of tissue transplant into the human nervous system.
The quasi-steady-state distribution volume of brain glucose was measured using 3-O-[14C]methylglucose quantitative autoradiography in a group of rats (n = 5) which 12-15 weeks previously had undergone unilateral ibotenic acid-induced lesion of the nucleus basalis magnocellularis, followed by implantation into ipsilateral neocortex of primordial basal forebrain cell suspensions. The effects of the lesion and the presence of transplanted tissue in neocortex were visualized by acetylcholinesterase histochemistry. The 3-O-[14C]methylglucose tracer was distributed homogeneously throughout the host brain areas analysed, with no side-to-side differences, despite a marked unilateral depletion of acetylcholinesterase activity ipsilateral to the lesion site. Whilst the transplants were indistinguishable from the homogeneity of surrounding host frontal cortex, there was a 70% increase in the apparent distribution volume of methylglucose localized around the ibotenate injection site and associated needle tract. Brain glucose content is an important experimental variable affecting the lumped constant of the 2-deoxyglucose technique. There was no evidence of any significant difference in the lumped constant between transplant and host tissue which might compromise the validity of the 2-deoxyglucose technique when used together with intracerebral implantation of fetal neuronal cell suspensions.
Thyroid and thymus tissue autografts were used to examine the suitability of different transplant sites in the pig for endocrine tissue transplantation. The omental pouch, gall bladder fossa and renal subcapsular space showed optimal implantation, preservation and vascularisation of graft tissue. Marked dissemination of graft tissue was observed at intramuscular sites and graft viability at subcutaneous sites in the ear was poor. The omental pouch represents a potentially suitable site for pancreatic islet tissue transplantation studies in the pig.
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Recent research using fetal tissue transplants has expanded possible treatment options for several traumatic and degenerative neurologic disorders. However, the expectations of therapeutic benefit to be gained from these methods have been challenged by an equivalent degree of controversy. Fundamental viewpoints regarding abortion, physical autonomy and the principle of harm have been raised against continuing research and the use of fetal tissue transplants. In this article, we first attempt to elucidate the practice, potential and limitations of such techniques. The critical, yet unresolved issues of supply and sources of fetal tissue are also discussed. In light of these concepts, we examine certain pertinent obligations and ethical concerns that may clarify the nurses' role in dealing with cases involving the use of fetal tissue transplants.
Functional vascular connections must form rapidly to prevent ischemic damage to grafted neural tissues. The temporal sequence by which transplant circulation is re-established provides information about the angiogenic capacity of either intact or damaged CNS blood vessels. This study compares the time course and mechanism of vascular reperfusion in allografts of superior cervical ganglia or adrenal medulla inserted either into the fourth ventricle or directly into the parietal cortex of perinatal rats. Tritiated thymidine was administered to recipients to determine angiogenic patterns at various postoperative time periods. After processing for light microscopic autoradiography, host and graft endothelial labelling indices were determined in order to establish the temporal sequence and location of vascular proliferation. Correlative electron microscopy depicted the morphological changes in transplant vasculature. Some recipients were prelabelled with 3H thymidine prior to transplantation to determine if host vessels invaded the grafts. Intraventricular graft vessels initially collapsed but sustained minimal ischemic damage and were completely reperfused by 24 hours postoperative. Adjacent intact host vessels attained peak 3H thymidine incorporation at 20 hours. Intrinsic graft vessels were radioactively labelled only after 48 hours. Intraparenchymal transplants surrounded by minimal trauma exhibited a similar temporal sequence of reperfusion and host endothelial proliferation. Intrinsic graft vessels in intraparenchymal grafts sustained more severe damage. With increased trauma, a concomitant delay in graft reperfusion time was observed. Grafts within prelabelled hosts rarely contained any labelled endothelium, indicating that anastomotic connections were made between original, intrinsic graft vessels and nearby host vascular sprouts. This study demonstrates that mature autonomic tissue stimulates the growth of adjacent host vessels when transplanted to undamaged brain surfaces. The anastomosis of nascent host vessels with pre-existing graft vessels is responsible for the rapid re-establishment of circulation within the transplants. A similar mechanism occurs within intraparenchymal grafts, although the rapidity of reperfusion appears to be predicated on the amount of trauma present at the graft site.
Use of a small diameter (5.1 cm) radiofrequency coil provided relatively high resolution magnetic resonance (MR) images of rat heads at 0.14 Tesla. On T1-weighted images, the rat brain was clearly visible in the rat head as a region of high signal intensity. No structures were distinguished within the normal rat brain. In contrast, in the brains of rats receiving unilateral kainic acid lesions of the striatum, enlarged lateral ventricles, which are characteristic of the lesion, were clearly visible as dark areas of low signal intensity. Extrastriatal damage on the lesioned side of the brain was also evident in some of the images. Fetal striatal tissue transplants growing within the lesioned striata were also identified in the MR images. The transplanted tissue appeared as areas of high and intermediate signal intensity, similar to the host brain. MR imaging is a useful technique for monitoring excitotoxin lesions of brain and fetal striatal tissue transplants in vivo.
Hyperplasia of the parathyroid glands usually is treated surgically by total parathyroidectomy, which would deprive the patient of the parathormone essential for calcium metabolism. The postoperative management of patients submitted to total parathyroidectomy consists either in oral administration of vitamin D and calcium, or in the transplantation of parathyroid tissue, which would produce the required parathormone. The purpose of this study is the scintigraphic assessment of parathyroid tissue transplantation patients. Eighteen patients were examined in the immediate and during a later postoperative period. The examination had three parts. The first one consisted of the assessment of the viability and function of the transplant by dynamic study, using TI-201. The second part consisted of the acquisition of static images of the transplant, and the third part was investigation for possible remnants of pathologic parathyroid tissue in the neck by dual tracer (TI-201/Tc-99m) subtraction imaging.
Previous experiments have proven brain tissue transplantation effective in reversing lesion-induced behavioral deficits in mature rats. This study reversed the usual experimental paradigm, so that fetal substantia nigra was transplanted into intact neonatal rats and allowed to mature in the host brain. Upon maturation substantia nigra lesions were made bilaterally to reveal the functional contribution of the transplanted tissue. In control animals these lesions depleted striatal dopamine, producing rigidity, poverty of movement and abnormal posture comparable to Parkinson's disease in the human; cessation of feeding and drinking led to progressive weight loss and death. In contrast, fetal substantia nigra transplanted into the neonatal rat became well-integrated in the host brain and was shown to protect the animal from this syndrome produced by subsequent substantia nigra lesions. We suggest that transplantation in these neonatal rats was performed during a crucial period of synaptogenesis, an environment particularly favorable to host-transplant interaction.
Ethical controversy over transplantation of human fetal tissue has arisen because the source of tissue is induced abortions. Opposition to such transplants has been based on various arguments, including the following: rightful informed consent cannot be obtained for use of fetal tissue from induced abortions, and fetal tissue transplantation might result in an increase in the number of abortions. These arguments were not accepted by the National Institutes of Health (NIH) Human Fetal Tissue Transplantation Research Panel. The majority opinion of the panel stated that abortion and fetal tissue use are entirely separate issues, and that tissue use is ethically acceptable because it can be morally insulated from the issue of abortion. In support of this view, panel members and others have replied to the arguments put forward by opponents of fetal tissue use. However, replies to the two arguments mentioned above have been unsatisfactory, and the shortcomings of those replies are identified herein. Examination of the arguments pro and con suggests that fetal tissue use cannot be completely insulated from the issue of abortion. Thus, in seeking an ethical justification for fetal tissue transplantation we must consider reasons other than those put forward by the NIH panel. In this paper it is argued that whatever wrong is involved in using fetal tissue from induced abortions must be balanced against the benefits for patients, and it is on this basis that fetal tissue transplantation can be ethically justified.
The ultrastructure of pancreatic light and clear endocrine cells in normal and transplanted tissue fragments in the anterior eye-chamber of rats was described by electron microscopy. Compared to the dark cells, the light cells contain a conspicuously poorly stained cytoplasmic ground substance with varying number of rough endoplasmic reticulum cisterns and secretory granules. The quantities of these two organelles are inversely proportional to each other. "Light" alpha, beta, delta and pancreatic polypeptide cell-types were identified in normal and transplanted tissue. Out of these, the light alpha cell is the most commonly occurring. The "clear" endocrine cells are much fewer in number than the light cells. They contain well stained cytoplasm with numerous low electron density vesicles and few secretory granules. There is no ultrastructural difference between the light and clear cells in normal and in transplanted tissue for 77 and 534 days. The occurrence of light and clear cells in the transplanted tissue shows that these transplants behave morphologically like normal tissue. These cell types might be related to the different stages of secretory granule synthesis and maturation.
The following factors are relevant to ethical considerations regarding fetal tissue transplantation for treatment of neurological disorders: the empirical status of human fetuses or abortuses, different purposes and sites of tissue retrieval or implantation, the therapeutic potential of the technique, the means through which tissue becomes available, possible motives, and possible donors and recipients of transplant tissue. After examining each of these, the author concludes that (1) only dead fetuses should be used as tissue sources, (2) decisions regarding abortion and transplantation should be kept separate, (3) anonymity between donor and recipient should be observed, and (4) buying and selling of fetal tissue should not be permitted.
Neural tissue transplantation has become recognized widely as a powerful experimental tool for studying structure-function relationships, development, plasticity, and capacities for regeneration in the adult CNS. In addition, this area of investigation has generated considerable interest in approaches that might be applicable to a variety of catastrophic neurological disorders. In this regard, attention has been given to neural tissue grafting as a potential therapeutic strategy in various forms of neurodegenerative disease. More recently, however, other investigations have begun to focus on the possible application of peripheral and central neural tissue transplants for promoting repair in forms of CNS trauma. This review highlights various neural transplantation approaches that have been explored primarily in the context of injury to the adult CNS, with emphasis on spinal cord injury. An overview is presented of the evolution of this area of research in terms of emerging biological perspectives, technological advances, and experimental modelling. Discussion centers on progress that has been made and a variety of theoretical and practical issues that remain to be resolved.
The tumors formed by rat C-6 glioma cells were isointense with the normal rat brain on precontrast T1 weighted magnetic resonance (MR) images. Following i.v. peripheral administration of the MR imaging contrast agent gadolinium (Gd)-DTPA, there was no significant change in the signal intensity from normal brain tissue. However, the tumor appeared as areas of high signal intensity demonstrating the abnormal vascular properties of the tumor. Fetal rat striatal tissue transplanted into unlesioned adult rat striatum appeared isointense with the host brain on precontrast T1 weighted images and there was no evidence for enhancement of the transplanted tissue relative to host brain following i.v. administration of Gd-DTPA. Using this technique we found no evidence with respect to permeability of the contrast agent of an abnormal blood-brain barrier within the striatal transplant in vivo.
The liver morphology of fetal hepatic tissue transplanted into an ectopic location was investigated over one year period. Fetal liver fragments prepared from a maternal rat on the 18th or 19th day of pregnancy were injected into the splenic parenchyma of syngeneic rats using a 21 gauge needle. Histologically, the fetal liver did not essentially show any apparent lobular architecture or cord structure. The transplanted fetal hepatic tissues survived and formed hepatic cords in the spleen instead of undergoing degeneration and necrosis. Three characteristic features became complete during the 4 weeks following transplantation, namely; clumps of hepatocytes with obvious hepatic cords and sinusoids, markedly proliferating bile ducts and proliferating individual hepatocytes. Macroscopic nodules of the hepatocytes on the spleen were seen at about 6 months after transplantation. When the differentiation of the transplanted fetal hepatic tissue was compared with the development of a normal neonatal liver after birth, it was delayed by only about one week, while there was no proliferation of bile ducts in the normal neonatal liver. This experimental model provides a useful system for investigating liver regeneration and the mechanism of cell growth.
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Fetal spinal cord tissue was transplanted into either a hemisection or complete transection lesion site at lumbar levels of the adult rat spinal cord that had been produced 3, 6, or 11 weeks prior to grafting. Tissue sections containing the graft and adjacent regions of the host spinal cord were processed for calcitonin gene-related peptide immunoreactivity (CGRP-IR) 2-6 months later. Numerous CGRP-IR axons within laminae I, II, V and X of the host spinal cord were observed crossing the graft-host interface as they spread diffusely throughout the caudal-rostral extent of the transplants. Many of these immunolabeled axons terminated in a distinct bouton-like formation. These results indicate that within the chronically injured spinal cord at least one-specific neuronal population retains the potential for regrowth in a long-term injury condition and that this capacity for axonal elongation can be sustained by the presence of fetal spinal cord tissue grafts.