Transplantation of Human Fetal Tissue from Spontaneous Abortions to a Rodent Model of Parkinson's Disease

1996 ◽  
Vol 5 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Takeshi Kondoh ◽  
Lisa L. Pundt ◽  
Jeffrey P. Blount ◽  
John A. Conrad ◽  
Walter C. Low
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Transplantation ◽  
Functional Expression ◽  
Fetal Tissue ◽  
Growth Potential ◽  
Functional Improvement ◽  
Spontaneous Abortions ◽  
Nigrostriatal Pathway ◽  
Human Fetal Tissue

The use of human fetal tissue from elective abortions for cell transplantation therapies has been the subject of considerable controversy. Because of concerns regarding the use of tissue from elective abortions, tissue from spontaneous abortions has been suggested as an alternate donor source. In the present study we have evaluated human fetal tissue from spontaneous abortions to assess its viability, growth potential, and functional expression. Viable cells (Grade I) from a donor (7 wk postconception) were transplanted as a suspension into the striatum of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway. A second group of animals received solid grafts of tissue from a Grade I donor 14 wk postconception. Tissue from Grade II and III specimens were not sufficiently viable for transplantation. Locomotor responses were monitored over a period of 15 wk and revealed an amelioration of rotational asymmetry by animals that received tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor showed no functional improvement. We found numerous graft-derived tyrosine hydroxylase (TH) immunopositive neurons contained within the transplantation site, and a rich plexus of TH-immunopositive fibers extending into the striatum of animals receiving tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor exhibited tissue necrosis at the transplant site and were devoid of TH-immunopositive neurons. These results suggest that human fetal ventral mesencephalic cells from spontaneous abortions can survive and develop after transplantation, and rectify locomotor deficits associated with experimental parkinsonism if the donor tissue is of the appropriate gestational age at the time of implantation. Our study further suggests, however, that the availability of tissue from spontaneous abortions of sufficient viability is quite limited and may thus restrict its potential use in cell transplantation therapies for Parkinson's disease.

Neural Tissue Xenotransplantation: What is Needed Prior to Clinical Trials in Parkinson's Disease?

2000 ◽  
Vol 9 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Roger A. Barker ◽  
A. Lisa Kendall ◽  
Håkan Widner ◽  
H. Widner ◽  
L. Larsson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Human Tissue ◽  
Neural Tissue ◽  
Fetal Tissue ◽  
Suitable Material ◽  
Human Fetal Tissue ◽  
Critical Issues ◽  
Alternative Sources

Embryonic allografted human tissue in patients with Parkinson's disease has been shown to survive and ameliorate many of the symptoms of this disease. Despite this success, the practical problems of using this tissue coupled to the ethical restrictions of using aborted human fetal tissue have lead to an exploration for alternative sources of suitable material for grafting, including xenogeneic embryonic dopaminergic-rich neural tissue. Nevertheless, xenografted neural tissue itself generates a number of practical, ethical, safety, and immunological issues that have to be addressed prior to any clinical xenotransplant program. In this article we review these critical issues and set out the criteria that we consider need to be met in the development of our clinical xenotransplantation research programs. We advocate that these, or similar, criteria should be adopted and made explicit by other centers contemplating similar clinical trials.

Utility of Fragmented Human Fetal Tissue as a Potential Dopaminergic Brain Graft in Parkinson's Disease

1993 ◽  
Vol 61 (1) ◽  
pp. 1-11 ◽  
Author(s):  
R.I. HogenEsch ◽  
M.J. Staal ◽  
I.P. Kema ◽  
C.H.C.M. Buys ◽  
K.G. Go
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Fetal Tissue ◽  
Human Fetal Tissue

scholarly journals Neural Transplantation in Parkinson's Disease

1997 ◽  
Vol 24 (04) ◽  
pp. 292-301 ◽  
Author(s):  
V. Mehta ◽  
J. Spears ◽  
I. Mendez
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Medical Management ◽  
Neurodegenerative Disorder ◽  
Fetal Tissue ◽  
Neural Transplantation ◽  
Current Status ◽  
Neurosurgical Procedures ◽  
Nigrostriatal Pathway

ABSTRACT:Parkinson's disease is a neurodegenerative disorder that affects about 1% of Canadians between the ages of fifty and seventy. The medical management for these patients consists of drug therapy that is initially effective but has limited long term benefits and does not alter the progressive course of the disease. The recalcitrance of longstanding Parkinson's disease to medical management has prompted the use of alternative surgical therapies. Many neurosurgical procedures have been utilized in order to improve the disabling symptoms these patients harbour. Although most of the current procedures involve making destructive lesions within various basal ganglia nuclei, neural transplantation attempts to reconstitute the normal nigrostriatal pathway and restore striatal dopamine. The initial success of neural transplantation in the rodent and primate parkinsonian models has led to its clinical application in the treatment of parkinsonian patients. Currently, well over one hundred patients throughout the world have been grafted with fetal tissue in an effort to ameliorate their parkinsonian symptoms. Although the results of neural transplantation in clinical trials are promising, a number of issues need to be resolved before this technology can become a standard treatment option. This review focuses on the current status of neural transplantation in Parkinson's disease within the context of other surgical therapies in current use.

scholarly journals Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Elisabetta Tronci ◽  
Camino Fidalgo ◽  
Manolo Carta
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Transplantation ◽  
Open Label ◽  
Double Blind ◽  
Clinical Investigations ◽  
Serotonin Neurons ◽  
Ventral Mesencephalic ◽  
Preclinical And Clinical Studies ◽  
Foetal Cell

Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson’s disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID.

scholarly journals Grafting of Encapsulated Dopamine-Secreting Cells in Parkinson's Disease: Long-Term Primate Study

2000 ◽  
Vol 9 (5) ◽  
pp. 705-709 ◽  
Author(s):  
Isao Date ◽  
Tetsuro Shingo ◽  
Hideyuki Yoshida ◽  
Kenjiro Fujiwara ◽  
Kazuki Kobayashi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Tumor Formation ◽  
Functional Improvement ◽  
Functional Changes ◽  
Polymer Encapsulation ◽  
Encapsulated Cells ◽  
Fluid Analysis

The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the primate brain in the long term and to effect functional improvement in the animals. Following polymer encapsulation, PC12 cells were transplanted into the striatum of hemiparkinsonian monkeys. The secretion of L-dopa and dopamine from the encapsulated cells, the morphology of these cells, the histology of the host striatum surrounding the capsule, and functional changes in the host animals were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the PC12 cells survived and continued to release L-dopa and dopamine even 12 months after transplantation. The histological response of the host brain surrounding the capsules was minimal and there were no signs of immunological rejection or tumor formation. The physical condition of the host animals was good for 12 months, and hematologic and cerebrospinal fluid analysis revealed that no animals suffered from infection or immunological reaction. These PC12 cell-grafted monkeys showed improvements in hand movements after transplantation, effects that lasted for at least 12 months. These results further support the potential use of this approach for the treatment of Parkinson's disease.

scholarly journals Dopamine cell transplantation in Parkinson's disease: challenge and perspective

2011 ◽  
Vol 100 (1) ◽  
pp. 173-189 ◽  
Author(s):  
Yilong Ma ◽  
Shichun Peng ◽  
Vijay Dhawan ◽  
David Eidelberg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Transplantation ◽  
Dopamine Cell
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