Autopsy findings in a patient who had an adrenal‐to‐brain transplant for Parkinson's disease

Peterson, Donald I.; Price, M.L.; Small, Clay

doi:10.1212/wnl.39.2.235

Cited by 139 publications

(21 citation statements)

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“…We propose that the poor survival of grafted chromaffin cells previously observed by our group Bing et al, 1990;Kordower et al, 1990a,b, 199 1) and others (Herrera-Marschitz et al, 1984;Morihisa et al, 1984;Stromberg et al, 1984;Freed et al, 1986;Bankiewicz et al, 1988;Frank et al, 1988;Hurtig et al, 1989;Jankovick et al, 1989;Peterson et al, 1989;Hirsch et al, 1990;Waters et al, 1990) is not due to the lack of NGF-mediated trophic support as previously believed. Rather, the fibroblasts and/or endothelial cells within the adrenal medulla appear deleterious to the viability of adrenal medullary grafts, an effect that can be overcome by NGF administration (Stromberg et al, 1985) or cografting with growth factor-producing cells Date et al, 1990a,b;Kordower et al, 1990a,b;Cunningham et al, 1991;Doering, 199 1;Chalmers et al, 1992).…”

Section: Discussionsupporting

confidence: 59%

“…Some studies failed to demonstrate the survival of histochemically identified grafted chromaffin cells for more than 400 min (Herrera-Marschitz et al, 1984;StrGmberg et al, 1984), and macrophages and inflammatory cells appear to be the principal cell types within the graft region. Recent postmortem analyses of patients receiving chromaffin cell implants confirmed findings reported in nonhumans (Frank et al, 1988;Hurtig et al, 1989;Jankovick et al, 1989;Peterson et al, 1989;Hirsch et al, 1990;Waters et al, 1990), with only one study demonstrating the survival of a few tyrosine hydroxylase (TH)-immunoreactive cells (Kordower et al,199 1).…”

mentioning

confidence: 79%

“…These studies have consistently reported poor viability of grafted cells (Morihisa et al, 1984;Bankiewicz et al, 1988Bankiewicz et al, , 1990aHansen et al, 1988Hansen et al, , 1989. Furthermore, all autopsy studies from Parkinson disease patients receiving adrenal chromaffin cell autografts have revealed poor chromaffin cell survival (Frank et al, 1988;Hurtig et al, 1989;Jankovick et al, 1989;Peterson et al, 1989;Hirsch et al, 1990;Waters et al, 1990), with only one case demonstrating a few viable TH-immunoreactive grafted cells (Kordower et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

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Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability

et al. 1993

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Previous investigations have demonstrated that adrenal chromaffin cells survive poorly when grafted into the striatum of rodents, nonhuman primates, and patients with Parkinson's disease. This poor survival has been attributed to the low levels of endogenous NGF within the striatum. However, chromaffin cells isolated from the nonchromaffin constituents of the adrenal medulla (fibroblasts and endothelial cells) have recently been demonstrated to survive grafting into a number of CNS sites. The present study determined whether nonchromaffin constituents of the adrenal medulla may be responsible for poor graft survival. We compared the survival of intrastriatally grafted isolated bovine chromaffin cells with that observed following implantation of either perfused adrenal medullary suspensions containing all adrenal medullary cell types or isolated chromaffin cells that were then reseeded with autologous fibroblasts and endothelial cells. Implants of perfused adrenal medullary cells survived poorly and most graft sites were infiltrated with macrophages. The chromaffin cells in this group that did survive appeared to be in the process of degeneration. In contrast, large numbers of isolated chromaffin cells survived for up to 2 months following transplantation. These cells maintained their endocrine phenotype and stained for all enzymatic markers of catecholamine synthesis as well as chromogranin A. Morphologically, these cells resembled chromaffin cells seen in situ and the perigraft region was essentially devoid of macrophages. When isolated chromaffin cells were reseeded with autologous fibroblasts and endothelial cells, the implants degenerated and few, if any, surviving chromaffin cells were observed. Interestingly, these latter grafts induced a host- derived sprouting response of tyrosine hydroxylase-immunoreactive fibers. These data demonstrate that large numbers of adrenal chromaffin cells can survive intrastriatal implantation in the absence of exposure to exogenous NGF. Rather, the nonchromaffin cells of the adrenal medulla (fibroblasts and endothelial cells) appear to compromise the viability of grafted chromaffin cells. Once they are eliminated from the graft, robust survival of chromaffin cells occurs. If clinical trials employing adrenal medullary grafts are still to be considered for the treatment of Parkinson's disease, isolation of the chromaffin cells should be considered to enhance graft viability.

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability

et al. 1993

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“…Survival of chromaffin cells transplanted into the brain parenchyma is, however, generally poor (Freed et al, 1986;Bohn et al, 1987;Hansen et al, 1988;Hurtig et al, 1989;Jankovic et al, 1989;Peterson et al, 1989;Hirsch et al, 1990;Kordower et al, 199 1). To increase the survival of grafted chromaffin cells, supplementation with NGF has been successfully employed (Stromberg et al, 1985;Date et al, 1990;Kordower et al, 1990;Cunningham et al, 1991).…”

mentioning

confidence: 99%

Enhanced survival and neuronal differentiation of adrenal chromaffin cells cografted into the striatum with NGF-producing fibroblasts

et al. 1995

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Although adrenal medullary chromaffin cells have been used extensively for intracerebral grafting, their survival has generally been poor. Improved survival of the implanted cells has been achieved by exposing the chromaffin cells to NGF in vivo. Culture studies have shown, however, that chromaffin cells are converted into sympathetic neurons when NGF is included in the medium. The degree to which such a transdifferentiation may occur in vivo has not been determined. We assessed the effects of cografting chromaffin cells with primary fibroblasts genetically engineered to express NGF. Chromaffin cells from 10 d old rats were implanted with NGF-producing or beta- galactosidase-producing primary fibroblasts (control fibroblasts) into the striatum of 6-hydroxydopamine treated adult rats of the same strain. Eight weeks postgrafting, chromaffin cells cografted with NGF- producing fibroblasts displayed many of the features of mature sympathetic neurons such as large somata, long processes, transmitter vesicles similar to those found in neurons, and positive immunolabeling for the neuronal markers neurofilament, MAP2 and SCG10. Chromaffin- derived neuron number was also significantly enhanced in the presence of NGF-producing fibroblasts. While control fibroblasts were also found to increase chromaffin cell number above that of chromaffin cells grafted alone, the control fibroblasts did not induce neuronal transdifferentiation. These results demonstrate that chromaffin cells cografted with NGF-producing fibroblasts undergo transdifferentiation in vivo and express many characteristics of mature sympathetic neurons. The consequences of this transdifferentiation on the long term survival and function of the transplanted cells in vivo remain to be clarified.

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“…In spite of the political controversy involving this pioneer studies, the clinical improvement obtained in some patients set off the interest of transplant therapy in PD patients around the world (Deacon et al, 1997;Freed 1990Freed , 2001Hirsch et al, 1990;Itakura et al, 1997;Kordower 1995Kordower , 1996Lindvall et al, 1990;Peterson et al, 1989;Sawle et al, 1992;Watts et al, 2003) (See table 2). However, the employment of human fetal dopaminergic neurons as a DA source for transplant is a complicated approach, due to its availability, which is imposed by ethical affairs; for this reason, they have been only employed in some human cases (Freed et al, 1990;Hauser et al, 1999;Kordower et al, 1995;Lindvall, et al, 1990;Madrazo et al, 1988;Mendez et al, 2008;Sawle et al, 1992).…”

Section: Transplant Therapy In Pd Patients: a Leap Forward To A Potenmentioning

confidence: 99%

Cell Therapy for Parkinson’s Disease: Failure or Success?

Guerra-Crespo¹,

Herrán-Arita²,

Hernández‐Cruz³

et al. 2011

Stem Cells in Clinic and Research

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Autopsy findings in a patient who had an adrenal‐to‐brain transplant for Parkinson's disease

Abstract: Autopsy findings in a patient who had an adrenal-to-brain transplant for Parkinson's disease 4 months before his death showed adrenal tissue in the basal ganglia, but it was necrotic. Symptomatic improvement lasted for only 2 weeks.

Cited by 139 publications

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Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability

Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability

Enhanced survival and neuronal differentiation of adrenal chromaffin cells cografted into the striatum with NGF-producing fibroblasts

Cell Therapy for Parkinson’s Disease: Failure or Success?

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