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

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.

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.

Infectious disease issues in fetal tissue transplantation for Parkinson's disease

1993 ◽  
Vol 12 (9) ◽  
pp. 65-67
Author(s):  
Margarita Cancio ◽  
Thomas Rushton ◽  
Thomas B. Freeman ◽  
C.W. Olanow ◽  
John S. Sarzier ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Fetal Tissue ◽  
Tissue Transplantation ◽  
Fetal Tissue Transplantation

scholarly journals Informed Consent and Sham Surgery as a Placebo in Fetal Cell Transplant Therapy Research for Parkinson’s Disease

2016 ◽  
Vol 20 (1) ◽  
pp. 14
Author(s):  
Joshua David Rosenberg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Informed Consent ◽  
Fetal Tissue ◽  
Control Group ◽  
Cell Transplant ◽  
Research Subjects ◽  
Double Blind ◽  
Sham Surgery ◽  
Fetal Tissue Transplantation

Fetal cellular transplantation therapy research in Parkinson’s Disease has raised important ethical questions from its beginning. One of the most hotly debated aspects of the recent clinical research has been the use of sham surgery as a placebo for the control group. Ethicists and researchers have focused on the unique risk surgical placebos pose to research subjects as compared to conventional, medical placebos. This review will deal with informed consent and the use of use of sham surgery in the placebo arm of recent fetal tissue transplantation randomized, placebo controlled, double blind, clinical trials. Do current procedures for obtaining informed consent meet the challenge of adequately informing patients enrolling in experiments with significant risks not only in the experimental group but also in the placebo group?

scholarly journals Single Cell Gene Expression Analysis Reveals Human Stem Cell-Derived Graft Composition in a Cell Therapy Model of Parkinson’s Disease

2019 ◽  
Author(s):  
Katarína Tiklová ◽  
Sara Nolbrant ◽  
Alessandro Fiorenzano ◽  
Åsa K. Björklund ◽  
Yogita Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Single Cell ◽  
Fetal Tissue ◽  
Fetal Cell ◽  
Term Survival ◽  
Cell Replacement ◽  
A Cell ◽  
Graft Composition

Since the pioneering studies using fetal cell transplants in Parkinson’s disease (PD), brain repair by cell replacement has remained a long-standing and realistic goal for the treatment of neurodegenerative disorders including PD. Authentic and functional midbrain dopamine (DA) neurons can now be generated from human pluripotent stem cells (hPSCs) via a floor plate intermediate1,2, and these cell preparations are both safe and functional when transplanted to animal models of PD3. However, although resulting grafts from fetal brain tissue and hPSCs contain large numbers of desired DA neurons, these therapeutic cells are a minor component of the grafts. Moreover, the cellular composition of the graft has remained difficult to assess due to limitations in histological methods that rely on pre-conceived notions concerning cell types. Here, we used single cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from ventral midbrain (VM)-patterned human embryonic stem cells (hESCs) and VM fetal tissue after long-term survival and functional maturation in a pre-clinical rat model of PD. The analyses revealed that while both cell preparations gave rise to neurons and astrocytes, oligodendrocytes were only detected in grafts of fetal tissue. On the other hand, a cell type closely resembling a class of newly identified perivascular-like cells was identified as a unique component of hESC-derived grafts. The presence of these cells was confirmed in transplants from three different hESC lines, as well as from iPSCs. Thus, these experiments have addressed one of the major outstanding questions in the field of cell replacement in neurological disease by revealing graft composition and differences between hESC- and fetal cell-derived grafts, which can have important implications for clinical trials.

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