scholarly journals Glial cell line–derived neurotrophic factor–supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage

2002 ◽  
Vol 13 (5) ◽  
pp. 1-6 ◽  
Author(s):  
Adam O. Hebb ◽  
Kari Hebb ◽  
Arun C. Ramachandran ◽  
Ivar Mendez
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Fetal Tissue ◽  
Cresyl Violet ◽  
Control Group ◽  
Long Term Storage ◽  
Cell Counts ◽  
Fresh Culture

Object Investigation of fetal dopaminergic tissue transplantation is being conducted in animal models and clinical trials as a potential treatment for advanced Parkinson disease (PD). Because the availability of fetal tissue is limited, however, the duration of its storage prior to transplantation is a key practical issue. Longer storage times may enable fetal tissue obtained over several days to be pooled together for transplantation in a recipient. Glial cell line–derived neurotrophic factor (GDNF) has been shown to improve survival of stored human dopaminergic tissue prior to transplantation. The objective of this study was to evaluate GDNF-supplemented hibernation of fetal dopaminergic tissue for extended periods of 6 to 15 days. Methods A total of 27 rat ventral mesencephalons (VMs) were obtained in gestation Day 14 rat fetuses, and three were cultured immediately (fresh-culture control group). The remaining 24 VMs were divided sagittally along the mid-line to form 48 equal pieces of hemimesencephalons. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 “partner” hemimesencephalons were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and cresyl violet. Cell counts for all cultures and percentage of TH-immunoreactive cells were obtained. The percentage of TH-positive cells for the fresh control group was 6.3 ± 0.5%; that measured in cultures derived from tissue hibernated in GDNF-supplemented medium was significantly increased at 6 and 9 days posthiber-nation compared with the fresh-culture control group and the partner groups stored in hibernation medium only. No significant increase in percentage of TH-immunoreactive cells was observed in the 12- and 15-day hibernation groups. Conclusions In summary the authors found that fetal dopaminergic tissue can safely be stored up to 9 days in GDNF-supplemented hibernation medium. Furthermore the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-positive cells prior to transplantation. These observations may have important clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.

Glial cell line—derived neurotrophic factor—supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage

2003 ◽  
Vol 98 (5) ◽  
pp. 1078-1083 ◽  
Author(s):  
Adam O. Hebb ◽  
Kari Hebb ◽  
Arun C. Ramachandran ◽  
Ivar Mendez
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Storage Time ◽  
Fetal Tissue ◽  
Control Group ◽  
Content Type ◽  
Cell Counts ◽  
Fine Print

Object. Transplantation of fetal dopaminergic tissue is being investigated in animal models and clinical trials for its potential as a treatment for advanced Parkinson disease. At the same time, the availability of fetal tissue is limited, making its storage time prior to transplantation a key practical issue. Although it results in a smaller percentage of surviving cells, a longer storage time enables fetal tissue obtained over several days to be pooled for transplantation in a recipient. Glial cell line—derived neurotrophic factor (GDNF) has been shown to improve survival of human dopaminergic tissue that has been stored prior to transplantation. The objective of this study was to evaluate the effects on fetal dopaminergic tissue of GDNF-supplemented hibernation for extended periods of 6 to 15 days. Methods. The ventral mesencephalon (VM) was harvested in a total of 27 14-day-old rat fetuses, and three VMs were cultured immediately (fresh control group). The remaining 24 VMs were divided sagittally along the midline to yield 48 equal pieces of hemimesencephalon. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 “partner” hemimesencephalon pieces were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and double-stained with cresyl violet. Cell counts for all cultures and the percentage of TH-immunoreactive cells were obtained. The percentage of TH-immunoreactive cells for the fresh control group was 6.3 ± 0.5%. The percentage of TH-immunoreactive cells in cultures derived from tissue stored in GDNF-supplemented medium was significantly increased at 6 and 9 days posthibernation compared with the fresh control group and the “partner” groups stored in hibernation medium only. No significant increase in the percentage of TH-immunoreactive cells was observed in the 12- and 15-day groups. Conclusions. In this study the authors have demonstrated that fetal dopaminergic tissue can be safely stored for up to 9 days in GDNF-supplemented hibernation medium. Furthermore, the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-immunoreactive cells prior to transplantation. These observations have practical clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.

Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease

10.1038/nm850 ◽  
2003 ◽  
Vol 9 (5) ◽  
pp. 589-595 ◽  
Author(s):  
Steven S. Gill ◽  
Nikunj K. Patel ◽  
Gary R. Hotton ◽  
Karen O'Sullivan ◽  
Renée McCarter ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor

scholarly journals Enhancement of graft survival and sensorimotor behavioral recovery in rats undergoing transplantation with dopaminergic cells exposed to glial cell line-derived neurotrophic factor

1999 ◽  
Vol 7 (3) ◽  
pp. E6
Author(s):  
Vivek Mehta ◽  
Murray Hong ◽  
Julian Spears ◽  
Ivar Mendez
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Fetal Tissue ◽  
Cell Number ◽  
Genetically Engineered ◽  
Nigrostriatal Pathway ◽  
Behavioral Recovery ◽  
Additional Improvement ◽  
6 Hydroxydopamine

The goal of this study was to investigate the ability of fetal dopaminergic neurons to improve complex sensorimotor behavior. The authors obtained ventral mesencephalic tissue from 14-day-old rat fetuses. The cells were exposed to glial cell line-derived neurotrophic factor (GDNF) prior to transplantation into rats with unilateral 6-hydroxydopamine lesions of the dopaminergic nigrostriatal pathway. Animals that received 400,000 cells exposed to GDNF demonstrated significant improvement in contralateral forelimb function and showed improvement in rotational behavior faster than animals that received cells not exposed to GDNF. Increasing the number of implanted cells to 800,000 exposed to GDNF did not result in any additional improvement in functional recovery. As neural grafting procedures in the nervous system evolve and genetically engineered cells or stem cells replace fetal tissue, crucial questions about cell number and trophic regulation will need to be addressed. This study demonstrates that grafting of 400,000 cells exposed to GDNF before transplantation has a beneficial effect in the restoration of complex sensorimotor behavior.

Early transplantation of an encapsulated glial cell line—derived neurotrophic factor—producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease

2005 ◽  
Vol 102 (1) ◽  
pp. 80-89 ◽  
Author(s):  
Takao Yasuhara ◽  
Tetsuro Shingo ◽  
Kenichiro Muraoka ◽  
Kazuki Kobayashi ◽  
Akira Takeuchi ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Rat Model ◽  
Neurotrophic Factor ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Glial Proliferation ◽  
Fine Print

Object. Glial cell line—derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)—treated dopaminergic neurons in vitro and in vivo. Methods. First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA—induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase—positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum. Conclusions. These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor α1. The results of this study support a role for this grafting technique in the treatment of PD.

scholarly journals Can Early Electrical Stimulation Accelerates the Neural Regeneration by Increasing the Expression of BDNF and GDNF in Distal Part of Injured Peripheral Nerve? An Animal Experimental Study

2021 ◽  
Vol 9 (A) ◽  
pp. 1006-1010
Author(s):  
Agus Roy Rusly Hariantana Hamid ◽  
Sri Maliawan ◽  
DPG Purwa Samatra ◽  
I Nyoman Mantik Astawa ◽  
I Made Bakta ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Sciatic Nerve ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Distal Part ◽  
Neural Regeneration ◽  
Control Group ◽  
Distal Nerve

BACKGROUND: The role of neurotrophic factors (brain-derived neurotrophic factors and glial cell line-derived neurotrophic factors) and early electrical stimulation (EES) in the injured nerve has found promising in several studies. However, there is still limited knowledge about the effect of EES in the distal part of the nerve to sustain this level of expression of growth factors. AIM: We aim to evaluate the effects of EES in in neural regeneration by measuring the expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in animal model. METHODS: The research was conducted starting from April to May 2021 using male Wistar rats. Using general anesthesia, the sciatic nerve was cut. The intervention group was treated with EES in the distal stump, right after nerve resection (20 Hz, 1–2 mA, 2–5 s), while the control group received no treatment after nerve resection. A reoperation on day 3 was performed in both groups to measure BDNF and GDNF expression level of the distal nerve tissue by ELISA as well as histopathological examination of sprouting axons of the injured proximal nerve. RESULTS: A total of 32 samples were included in the study. A statistically significant levels of GDNF is found higher in the EES group (n = 16) than the control group (n = 16) (35. 71 pg/100 mg, confidence interval (CI) 95% 23.93, 47.48, p < 0.05). The number of sprouting axons is found lower in the EES group (p < 0.05). The BDNF level is similar between the two groups, however not significant. After a subgroup analysis, it was found that the greater the level of GDNF, the fewer the axon sprouts in both groups (fewer axon group 58.35 [n = 22, CI 95% 45.14, 71.55] vs. more axon group 47.14 [n = 10, CI 95% 35.33, 58.95]), p < 0.05. CONCLUSION: The EES proves its benefit in accelerating the axonal regeneration by increasing the expression GDNF in the distal nerve stumps in the electrical excited degenerated sciatic nerve in the rat model.

scholarly journals Parkinson Disease-associated DJ-1 Is Required for the Expression of the Glial Cell Line-derived Neurotrophic Factor Receptor RET in Human Neuroblastoma Cells

2010 ◽  
Vol 285 (24) ◽  
pp. 18565-18574 ◽  
Author(s):  
Rossana Foti ◽  
Silvia Zucchelli ◽  
Marta Biagioli ◽  
Paola Roncaglia ◽  
Sandra Vilotti ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Neuroblastoma Cells ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma

Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease

2006 ◽  
Vol 59 (3) ◽  
pp. 459-466 ◽  
Author(s):  
Anthony E. Lang ◽  
Steven Gill ◽  
Nik K. Patel ◽  
Andres Lozano ◽  
John G. Nutt ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Controlled Trial ◽  
Randomized Controlled

230 EFFECT OF DIFFERENT CONCENTRATIONS OF GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR ON EXPRESSION OF SELF-RENEWAL RELATED GENES IN GOAT (CAPRA HIRCUS) SPERMATOGONIAL STEM CELLS

2016 ◽  
Vol 28 (2) ◽  
pp. 246
Author(s):  
A. Sharma ◽  
S. M. Shah ◽  
N. Saini ◽  
M. K. Singh ◽  
S. K. Singla ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Transforming Growth Factor ◽  
Spermatogonial Stem Cells ◽  
Capra Hircus ◽  
Control Group ◽  
Self Renewal ◽  
Percoll Density Gradient Centrifugation

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β superfamily produced by Sertoli cells, is essential for the self-renewal of spermatogonial stem cells in vivo. The present study evaluated the effects of different concentrations of GDNF (human recombinant expressed in Escherichia coli) on expression of some self-renewal related genes in spermatogonial stem cells (SSC). The SSC were isolated from prepubertal goat testes (3–6 months of age) by using double enzymatic digestion method and filtration through 80- and 60-µm nylon mesh filters. Further enrichment was achieved by differential plating on Datura stramonium agglutinin (DSA) lectin-coated dishes and Percoll density gradient centrifugation. The enriched cells were cultured on goat Sertoli cell feeder layer in DMEM + 10% fetal bovine serum at 37°C in a 5% CO2 incubator. Primary SSC colonies were formed within 7 to 10 days. These colonies were characterised through alkaline phosphatase and immunofluorescence staining on Day 10 for different SSC-specific protein markers. Colonies were found to be positive for DBA, THY1, PLZF, UCHL1, OCT-4, SOX2, and NANOG, and negative for c-Kit expression. These colonies were cultured for 15 days without or with supplementation of GDNF forming following groups: (1) without GDNF (control), (2) 10 ng mL–1 GDNF, (3) 20 ng mL–1 GDNF, and (4) 40 ng mL–1 GDNF. RNA was isolated from 100 colonies from 3 different trials on Day 15 of culture, and relative expression of different self-renewal related genes was determined by qRT-PCR. Relative mRNA abundance of PLZF was higher (P < 0.05) following supplementation with 40 ng mL–1 GDNF than in other groups (i.e. control, 10 and 20 ng mL–1 GDNF). Expression of BCL6B and ID4 was found to be significantly higher (P < 0.05) after supplementation of GDNF at all concentrations compared with the control group. Expression of UCHL1 was higher with addition of 20 and 40 ng mL–1 GDNF (P < 0.05), whereas expression of THY1 was higher with supplementation of 10 ng mL–1 GDNF (P < 0.05). In conclusion, GDNF was found to benefit expression of goat SSC candidate genes at a concentration of 40 ng mL–1.

Sign in / Sign up

Export Citation Format

Share Document