Robust survival of isolated bovine adrenal chromaffin cells following lntrastriatal transplantation

A novel hypothesis of adrenal graft viability

Sherry B. Schueler, John D. Ortega, Jacqueline Sagen, Jeffrey H. Kordower

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Previous investigations have demonstrated that adrenal chromaf fin cells survive poorly when grafted into the striatum of rodents, nonhuman primates, and patients with Parkinsons 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 nonchromaftin 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 endocrihe 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 chromaffincells 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 Parkinsons disease, isolation of the chromaffin cells should be considered to enhance graft viability.

Original languageEnglish
Pages (from-to)4496-4510
Number of pages15
JournalJournal of Neuroscience
Volume13
Issue number10
StatePublished - Dec 1 1993
Externally publishedYes

Fingerprint

Chromaffin Cells
Transplantation
Transplants
Survival
Adrenal Medulla
Endothelial Cells
Fibroblasts
Nerve Growth Factor
Graft Survival
Parkinson Disease
Macrophages
Chromogranin A
Tyrosine 3-Monooxygenase
Primates
Catecholamines
Rodentia
Suspensions
Clinical Trials

Keywords

  • Adrenal medulla
  • Chromaffin cells
  • Grafts
  • Parkinson's disease
  • Rats
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Robust survival of isolated bovine adrenal chromaffin cells following lntrastriatal transplantation : A novel hypothesis of adrenal graft viability. / Schueler, Sherry B.; Ortega, John D.; Sagen, Jacqueline; Kordower, Jeffrey H.

In: Journal of Neuroscience, Vol. 13, No. 10, 01.12.1993, p. 4496-4510.

Research output: Contribution to journalArticle

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