Ž . Brain Research 822 1999 246–250 Short communication Sertoli cells enhance the survival of co-transplanted dopamine neurons Alison E. Willing a, ) , Agneta I. Othberg a,1 , Samuel Saporta b , Alex Anton b , Stacy Sinibaldi b , Stephen G. Poulos a , Donald F. Cameron b , Thomas B. Freeman a , Paul R. Sanberg a a Neuroscience Program, DiÕision of Neurosurgery, UniÕersity of South Florida College of Medicine, 12901 Bruce B. Downs BouleÕard, Tampa, FL 33612, USA b Neuroscience Program, Department of Anatomy, UniÕersity of South Florida College of Medicine, 12901 Bruce B. Downs BouleÕard, Tampa, FL 33612, USA Accepted 29 December 1998 Abstract Ž . Ž . wx One of the major issues in neural transplantation is the low survival rate -5% of transplanted dopamine DA neurons 3 . Recently it has been shown that it is possible to enhance the survival of these neurons, which in turn may decrease the amount of tissue that is required for each transplantation patient. The present paper demonstrates a novel approach for enhancing neuronal survival by Ž . co-transplantation of neuronal tissue with Testis-derived Sertoli cells SC . This strategy could improve neuronal survival through the provision of trophic support. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Dopamine; Tyrosine hydroxylase; Trophic factor; Sertoli cell; Transplantation The SC is intrinsic to the testis where its function is to provide an appropriate environment for the development of the antigenic germ cells. They secrete numerous trophic factors and regulatory proteins, many of which have been shown to increase tyrosine hydroxylase expression and the survival of DA neurons, including insulin-like growth Ž . w x factor-I IGF-I 8,11 , basic fibroblast growth factor Ž . w x Ž bFGF 5,8,22,25 , transforming growth factors-a TGF- . wx w x Ž . a 2 and -b 14 , platelet-derived growth factor PDGF w x Ž . w x Ž . w x 6,17 , neurturin NTN 10 , interleukin 1a IL-1a 1,16 Ž . w x and interleukin 6 IL-6 27 . When SC are co-cultured Ž . with fetal ventral mesencephalon VM , there is an in- crease in the number of surviving TH-positive neurons w x 4,18,23 . Furthermore, the soma size and neuritic out- w x growth are enhanced 18 . When the VM tissue was co-cul- tured with peritubular cells of the testis, however, no increase in TH neuron survival was observed, suggesting that this trophic effect was specific to the SC. The purpose of the current in vivo study was to deter- mine whether allografts of Sertoli cells co-transplanted with dopaminergic neurons obtained from fetal rat ventral ) Corresponding author. Fax: q1-813-974-3078; E-mail: awilling@com1.med.usf.edu 1 Present address: Theracell Inc., Somerville, NJ 08876, USA. Ž . mesencephalon VM would enhance the survival of dopaminergic neurons transplanted into the 6-hydroxy- dopamine lesioned rat striatum. Ž . Male Sprague–Dawley rats 275–325 g were lesioned with 6-OHDA. The animals were maintained and handled in accordance with the NIH guidelines for the care and use Ž of animals. The rats were anesthetized with equithesin 3.5 . Ž mlrkg and a single injection of 6-OHDA Sigma, St. Louis, MO, USA; 2.5 ml, 3.6 mgrml in 0.2% ascorbic . acid was made at 4.4 mm posterior to bregma, y1.2 mm laterally and y7.8 mm ventral to dura with the toothbar set at y2.4 mm. The animals were allowed to recover from surgery for three weeks at which time they were Ž tested for motor asymmetry with apomorphine 0.2 mgrkg . s.c. every 3–4 days to verify the lesion. In order to be included in the study, each animal had to average at least 8 turnsrmin over the 30 min test on three occasions. Once the existence of the lesion was established, the animals were assigned to one of four groups: 24 h survival of VM alone or VM q SC and 7 day survival VM alone or VM q SC. The VM was isolated from E15 embryos and dissected in HBSS q 15 mM Hepes. The tissue was then Ž . incubated for 20 min at 378C in 0.1% trypsin Sigma and Ž . 0.05% DNase Sigma in HBSSrHepes, rinsed 5 times with 0.05% DNase, and mechanically dissociated using fire polished glass pipettes in a 100 ml volume. Viability 0006-8993r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 01128-2