Recombinant human GDNF protein (Qk051-CTG)

Product: Qk051-CTG Category: Cell Therapy Grade

Price range: £5,060.00 through £7,920.00

Recombinant human GDNF protein (Qk051-CTG)

Recombinant human GDNF protein (Qk051-CTG) - Image 2

Recombinant human GDNF protein (Qk051-CTG) - Image 3

Glial cell line-derived neurotrophic factor (GDNF) is a member of neurotrophin family, it plays a crucial role in the development, growth, and survival of neurons in particular midbrain dopaminergic neurons. GNDF is used to maintain neurons and cortical organoids and to differentiate dopaminergic neurons from human pluripotent stem cell-derived neural progenitors for neural regenerative therapy applications.

Recombinant human GDNF bioactive 30 kDa homodimer. This cell therapy grade protein is animal origin-free (AOF), carrier protein-free, and tag-free to ensure its purity with exceptional lot-to-lot consistency.

Qkine cell therapy grade high purity animal origin-free proteins are manufactured as GMP grade equivalents in an ISO 9001:2015-certified facility, under ISO 20399:2022 standards with GMP compliance, defined quality criteria and documentation.

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Price range: £5,060.00 through £7,920.00

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Summary:

High purity GDNF (Uniprot: P39905)

30.4 kDa (dimer)
Certified animal origin-free (AOF)
Cell and gene therapy grade
Manufactured in our ISO 9001:2015 facility in Cambridge, UK
Lot-to-lot consistency in bioactivity
Full traceability and documentation
Carrier protein-free, tag free
Expressed in E. coli
Lyophilized from acetonitrile, TFA
Resuspend in sterile-filtered water at >50 µg/ml, add carrier protein if desired, prepare single use aliquots and store frozen at -20 °C (short-term) or -80 °C (long-term).

Handling and storage FAQ

Featured applications:

Neurogenesis and neural differentiation
Neural stem cell (NSC) therapy
Regenerative stem cell therapy

Alternative protein names

Species reactivity

Alternative proteins

Recombinant human GDNF protein (Qk051)

GDNF activity was determined using a SH-SY5Y cell proliferation assay. Cells were incubated with different concentrations of GDNF in the presence of retinoic acid and recombinant GFR α1 for 3 days before viable cell measurement using an MTS assay. Data are n=2. EC50 = 18 ng/ml. Data from Qk051 batch #104372.

GDNF migrates as a single band at 30 kDa in non-reducing (NR) conditions and 15 kDa upon reduction (R). No contaminating protein bands are visible. Purified recombinant protein (3 µg) was resolved using 15% w/v SDS-PAGE in reduced (+β-mercaptothanol, R) and non-reduced (NR) conditions and stained with Coomassie Brilliant Blue R250. Data from Qk051 batch #104372.

Further quality assays

Mass spectrometry: single species with expected mass
Purity >98%, by SDS-PAGE quantitative densitometry
Recovery from stock vial: >95%
Sterility tested and mycoplasma negative
Endotoxin: <0.005 EU/μg protein (below level of detection)
Residual host cell protein <10 ng/µg
Residual host cell DNA <10 ng/μg
N-terminal sequence analysis

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MSDS file

We are a company founded and run by scientists to provide a service and support innovation in stem cell biology and regenerative medicine. All our products are exceptionally high purity, with complete characterisation and bioactivity analysis on every lot.

Protein background

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor and a member of the GDNF family of ligands (GFL) which include neurturin, artemin, and persephin [1,2]. GFLs regulate several biological processes including cell survival, cell proliferation, cell differentiation, cell migration, and neurite outgrowth [1,3,4]. GDNF protein plays a crucial role in the development, growth, and survival of neurons in particular midbrain dopaminergic neurons [5]. It promotes the axon growth and innervation of dopamine neurons. It also facilitates the differentiation of neural progenitors to astrocytes and is involved in neuroprotection[6,7]. In addition, it is involved in kidney development and spermatogenesis [8,9].

In cell culture, GDNF supports the survival and growth of neurons and astrocytes. It is used in combination with other growth factors to differentiate human induced pluripotent stem cell-derived neural progenitors into neurons and astrocytes. GDNF is used for the differentiation, survival, and maturation of dopaminergic neurons with brain-derived neurotrophic factor (BDNF), FGF-8a/FGF-8b, and Shh [10-13]. Glutamatergic and GABAergic neurons are obtained with combinations of BDNF, GDNF, NT-3, or insulin-like growth factor 1 (IGF-1) [14-16]. Also, the culture of cortical organoids requires BDNF and GDNF for maturation [17,18]. Finally, it can be used to generate and maintain astrocytes along with ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF) [19-21].

GDNF is mainly produced and released by glial cells such as astrocytes, Schwann cells, and satellite cells [22]. It is a homodimer of a molecular weight of 30 kDa which belongs to the cystine-knot protein family [1,23]. The GFLs act as biologically active homodimers that signal through the transmembrane RET receptor tyrosine kinase [24]. GFL activation of RET is dependent upon co-receptors, namely the four GDNF Family Receptor α (GFRα1-4). GFL signalling specificity arises from the preferentially binding of each ligand to one of the four GFRα receptors; GDNF preferentially binds GFRα1 with high affinity [1,24].

GDNF has shown promise in various therapeutic applications neurodegenerative diseases and disorders such as Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, peripheral nerve and spinal cord injuries [1,25]. The idea is to harness GDNF for clinical use to promote the survival and function of dopaminergic neurons, potentially slowing or reversing the progression of these diseases. Clinical trials using it has shown improved motor function in patients with Parkinson’s disease [26,27]. Finally, GDNF has also been proposed for the treatment of drug addiction and alcoholism [25].

Background references

[1] Airaksinen, M. S. & Saarma, M. The GDNF family: Signalling, biological functions and therapeutic value. Nat. Rev. Neurosci. 3, 383–394 (2002). doi: 10.1038/nrn812
[2] von dem Bussche, M. & Tuszynski, M. H. Growth Factors: Neuronal Atrophy. in Encyclopedia of Neuroscience (ed. Squire, L. R.) 987–992 (Academic Press, 2009). doi:10.1016/B978-008045046-9.00143-1.
[3] Airaksinen, M. S., Titievsky, A. & Saarma, M. GDNF Family Neurotrophic Factor Signaling: Four Masters, One Servant? Mol. Cell. Neurosci. 13, 313–325 (1999). doi: 10.1006/mcne.1999.0754
[4] Baloh, R. H., Enomoto, H., Johnson, E. M. & Milbrandt, J. The GDNF family ligands and receptors — implications for neural development. Curr. Opin. Neurobiol. 10, 103–110 (2000). doi: 10.1016/s0959-4388(99)00048-3
[5] Akerud, P., Alberch, J., Eketjäll, S., Wagner, J. & Arenas, E. Differential effects of glial cell line-derived neurotrophic factor and neurturin on developing and adult substantia nigra dopaminergic neurons. J. Neurochem. 73, 70–78 (1999). doi: 10.1046/j.1471-4159.1999.0730070.x
[6] Parsadanian, A., Pan, Y., Li, W., Myckatyn, T. M. & Brakefield, D. Astrocyte-derived transgene GDNF promotes complete and long-term survival of adult facial motoneurons following avulsion and differentially regulates the expression of transcription factors of AP-1 and ATF/CREB families. Exp. Neurol. 200, 26–37 (2006). doi: 10.1016/j.expneurol.2006.01.014
[7] Boku, S. et al. GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3. Biochem. Biophys. Res. Commun. 434, 779–784 (2013). doi.org/10.1016/j.bbrc.2013.04.011
[8] Costantini, F. & Shakya, R. GDNF/Ret signaling and the development of the kidney. BioEssays News Rev. Mol. Cell. Dev. Biol. 28, 117–127 (2006). doi.org/10.1002/bies.20357
[9] Hofmann, M.-C. Gdnf signaling pathways within the mammalian spermatogonial stem cell niche. Mol. Cell. Endocrinol. 288, 95–103 (2008). doi: 10.1016/j.mce.2008.04.012
[10] Granholm, A.-C. et al. Glial Cell Line-Derived Neurotrophic Factor Is Essential for Postnatal Survival of Midbrain Dopamine Neurons. J. Neurosci. 20, 3182–3190 (2000). doi.org/10.1523/JNEUROSCI.20-09-03182.2000
[11] Perrier, A. L. et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc. Natl. Acad. Sci. U. S. A. 101, 12543–12548 (2004). doi.org/10.1073/pnas.0404700101
[12] Brennand, K. et al. Modeling schizophrenia using hiPSC neurons. Nature 473, 221–225 (2011). doi: 10.1038/nature09915
[13] Kriks, S. et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480, 547–551 (2011). doi.org/10.1038/nature10648
[14] Fernandopulle, M. S. et al. Transcription-factor mediated differentiation of human iPSCs into neurons. Curr. Protoc. Cell Biol. 79, e51 (2018). doi: 10.1002/cpcb.51
[15] Li, X.-J. et al. Specification of motoneurons from human embryonic stem cells. Nat. Biotechnol. 23, 215–221 (2005). doi: 10.1038/nbt1063
[16] Lin, L., Yuan, J., Sander, B. & Golas, M. M. In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons. Stem Cells Transl. Med. 4, 775–788 (2015). doi: 10.5966/sctm.2014-0083
[17] McComish, S. F. & Caldwell, M. A. Generation of defined neural populations from pluripotent stem cells. Philos. Trans. R. Soc. B Biol. Sci. 373, 20170214 (2018). doi: 10.1098/rstb.2017.0214
[18] Jacob, F. et al. Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium. Cell Stem Cell 27, 937-950.e9 (2020). doi: 10.1016/j.stem.2020.09.016
[19] Krencik, R., Weick, J. P., Liu, Y., Zhang, Z. & Zhang, S.-C. Specification of Transplantable Astroglial Subtypes from Human Pluripotent Stem Cells. Nat. Biotechnol. 29, 528–534 (2011). doi: 10.1038/nbt.1877
[20] Serio, A. et al. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. Proc. Natl. Acad. Sci. U. S. A. 110, 4697–4702 (2013). doi.org/10.1073/pnas.1300398110
[21] Gunhanlar, N. et al. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells. Mol. Psychiatry 23, 1336–1344 (2018). doi.org/10.1038/mp.2017.56
[22] Rocha, S. M., Cristovão, A. C., Campos, F. L., Fonseca, C. P. & Baltazar, G. Astrocyte-derived GDNF is a potent inhibitor of microglial activation. Neurobiol. Dis. 47, 407–415 (2012). doi: 10.1016/j.nbd.2012.04.014
[23] Ibáñez, C. F. Emerging themes in structural biology of neurotrophic factors. Trends Neurosci. 21, 438–444 (1998). doi: 10.1016/s0166-2236(98)01266-1
[24] Takahashi, M. The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev. 12, 361–373 (2001). doi: 10.1016/s1359-6101(01)00012-0
[25] Hsieh, J. C. & Penn, R. D. Chapter 44 - Infusion Therapy for Movement Disorders. in Neuromodulation (eds. Krames, E. S., Peckham, P. H. & Rezai, A. R.) 561–570 (Academic Press, 2009). doi:10.1016/B978-0-12-374248-3.00045-8.
[26] Manfredsson, F. P. et al. The Future of GDNF in Parkinson’s Disease. Front. Aging Neurosci. 12, (2020). doi.org/10.3389/fnagi.2020.593572
[27] Barker, R. A. et al. GDNF and Parkinson’s Disease: Where Next? A Summary from a Recent Workshop. J. Park. Dis. 10, 875–891. doi: 10.3233/JPD-202004

Additional resources

FAQ

How is GDNF used in cell culture?

GDNF is used as a growth factor which is supplemented in cell culture media to promote the differentiation, growth, and maturation of dopaminergic neurons.

What is the difference between NGF, GDNF and BDNF?

NGF, GDNF, and BDNF are all part of the neurotrophins or neurotrophic factors family. They all regulate the development, growth, and survival of neurons and have more specific roles. NGF is associated with the growth and maintenance of sensory and sympathetic neurons. BDNF and GDNF are both associated with dopaminergic, glutamatergic, and GABAergic neurons. In addition, BDNF plays a crucial role in synapses formation whereas GDNF is involved in the growth and maintenance of other glial cells such as astrocytes.

What is the function of GDNF?

GDNF protein plays a crucial role in the development, growth, and survival of midbrain dopaminergic neurons.

Which cells release GDNF?

GDNF is mainly released by glial cells such as astrocytes, Schwann cells, and satellite cells.

Our products are for research use only and not for diagnostic or therapeutic use. Products are not for resale.

For use in manufacturing of cellular or gene therapy products. Not intended for in vivo applications.

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Recombinant human GDNF protein (Qk051-CTG)

Summary:

Featured applications:

Further quality assays

Protein background

Additional resources

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