Snake venom is a complex mixture of different compounds which have potential pharmacological properties and may affect mesenchymal stem cells (MSCs). In this study we investigate the effects of two Iranian vipers; vipera albicornuta and vipera latifii crude venoms on the viability of MScs in vivo and in vitro. The cells in in vitro tests were treated with different concentrations (1, 2, 3, 4 and 5 μg/100μl) of mentioned venoms for 24, 48 and 72 hours.
The cells in in vivo experiment only were treated with v. Latifii venom at the concentration of 1μg/100μl and time intervals as in vitro tests. The cell viability in in vitro experiment was assessed using MTT assay. The results of in vitro experiments showed that maximum cell viability was observed at concentrations of 1 and 2 μg/100μl of v. albicornuta and v. latifi ivenoms aft er 48 and 72 hours, respectively. The results of in vivo experiment showed that the cells treated with v. Latifii venom for 72 hours in situ have the highest proliferation rate after passages three, four and five in comparison to control. The results of this study showed that the v. albicornuta and v. latifi i venoms can affect the confluence and viability of the MSCs.
Mesenchymal stem cells, Venom, Viper snake, Cell culture, Bone marrow
Stem Cells in Hematopoietic Stem Cell Transplantation.
Allogeneic Stem Cell Transplant. 2010;477–90.
2. Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley
B, Hows JM. Adult bone marrow is a rich source of human
mesenchymal “stem” cells but umbilical cord and mobilized
adult blood are not. Br J Haematol. 2003;121(2):368–74.
3. Friedenstein A, Chailakhjan R, Lalykina K. the Development
of Fibroblast Colonies in Monolayer Cultures of Guinea. Cell
4. da Silva Meirelles L, Caplan AI, Nardi NB. In Search of the
In Vivo Identity of Mesenchymal Stem Cells. Stem Cells.
5. E. Hanson S, L. Th ibeault S, Hematti P. Clinical Applications
of Mesenchymal Stem Cells in Laryngotracheal Reconstruction.
Curr Stem Cell Res Th er. 2010;5(3):268–72.
6. Trounson A, Th akar RG, Lomax G, Gibbons D. Clinical trials
for stem cell therapies. Vol. 9, BMC Medicine. 2011. p. 52.
7. Udalamaththa VL, Jayasinghe CD,
Udagama PV. Potential role of herbal
remedies in stem cell therapy: proliferation
and diff erentiation of human
mesenchymal stromal cells. Stem Cell
Res Th er. 2016;7(1):1–8.
8. Mackessy SP. Th rombin-like enzymes
in snake venoms. Toxins Hemost
From Bench to Bedside. 2011;519–57.
9. Tu AT. Snake venoms: general background
and composition. Venoms
Chem Mol Biol. 1988;1–19.
10. Siigur E, Aaspõllu A, Siigur J. Sequence
diversity of Vipera lebetina
snake venom gland serine proteinase
homologs - Result of alternative-splicing
or genome alteration. Gene.
11. Kessler P, Ménez A, Michalet S,
Gilquin B, Servent D, Tzartos S, et al.
Relative Spatial Position of a Snake
Neurotoxin and the Reduced Disulfi
de Bond α(Cys 192 -Cys 193 )
at the αγ Interface of the Nicotinic
Acetylcholine Receptor. J Biol Chem.
12. Harvey AL. Natural products in drug
discovery. Drug Discovery Today.
Drug Discov Today. 2015;13:894–901.
13. Chan WY, Xia L, Chan YS, Cheung
RCF, Wong JH, Ng TB. Snake venom
toxins: toxicity and medicinal applications.
Appl Microbiol Biotechnol.
14. Lu Z, Lei D, Jiang T, Yang L, Zheng
L, Disease JZ-C death &, et al. Nerve
growth factor from Chinese cobra
venom stimulates chondrogenic differentiation
of mesenchymal stem
cells. NatureCom. 2017;8(5).
15. Li X, Chen M, Lei D, Yang B, Liao G-S,
Shu Y-Y, et al. Bioactivities of nerve
growth factor from Chinese cobra
venom. J Nat Toxins. 1999;8(3):359–
16. Asaoka Y, Yoshida K, Sasaki Y,
Nishizuka Y. Potential role of phospholipase
A2 in HL-60 cell diff erentiation
to macrophages induced by
protein kinase C activation. Proc Natl
Acad Sci U S A. 1993;90(11):4917–21.
17. Li W, Yeo LS, Vidal C, McCorquodale
T, Herrmann M, Fatkin D, et al. Decreased
bone formation and osteopenia
in lamin A/C-defi cient mice.
Vanacker J-M, editor. PLoS One. 2011
18. Gasparotto VPO, Landim-Alvarenga
FC, Oliveira ALR, Simões GF, Lima-
Neto JF, Barraviera B, et al. A new
fi brin sealant as a three-dimensional
scaff old candidate for mesenchymal
stem cells. Stem Cell Res Th er.
19. Kouchesfahani HM, Nabiuni M, Parivar
K, Ebrahimi S. Eff ect of honey bee
venom on diff erentiation of cholinergic
neurons. J Venom Res. 2010;1:29–
20. Chen HH, Decot V, Ouyang JP, Stoltz
JF, Bensoussan D, De Isla NG. In vitro
initial expansion of mesenchymal
stem cells is infl uenced by the culture
parameters used in the isolation process.
Biomed Mater Eng. 2009;19(4–
21. Sun Y, Zhang L, Wang H, Zhu H,
Wang H, Gao Y, et al. Soluble Tumor
Necrosis Factor Receptor 1 Released
by Skin-Derived Mesenchymal Stem
Cells Is Critical for Inhibiting Th 17
Cell Diff erentiation. Stem Cells Transl
Med. 2016 Mar;5(3):301–13.
22. Collins C, Liem M, Ravichandran
KS, Atkin-Smith GK, Mathivanan S,
Goodall KJ, et al. A novel mechanism
of generating extracellular vesicles
during apoptosis via a beads-on-astring
membrane structure. Nat Commun.
23. Valadi H, Ekström K, Bossios A,
Sjöstrand M, Lee JJ, Lötvall JO. Exosome-
mediated transfer of mRNAs
and microRNAs is a novel mechanism
of genetic exchange between cells. Nat
Cell Biol. 2007;9(6):654–9.
24. Pállinger É, László V, Pásztói M, Nagy
G, Pál Z, Kittel Á, et al. Membrane
vesicles, current state-of-the-art:
emerging role of extracellular vesicles.
Cell Mol Life Sci. 2011;68(16):2667–
25. Vlassov A V., Magdaleno S, Setterquist
R, Conrad R. Exosomes: Current
knowledge of their composition,
biological functions, and diagnostic
and therapeutic potentials. Vol. 1820,
Biochimica et Biophysica Acta - General
Subjects. 2012. p. 940–8.
26. Crescitelli R, Lässer C, Szabó TG, Kittel
A, Eldh M, Dianzani I, et al. Distinct
RNA profi les in subpopulations
of extracellular vesicles: Apoptotic
bodies, microvesicles and exosomes. J
Extracell Vesicles. 2013;2(1):20677.
27. Trummal K, Tõnismägi K, Paalme
V, Järvekülg L, Siigur J, Siigur E.
Molecular diversity of snake venom
nerve growth factors. Toxicon.
28. Nakashima S, Kitamoto K, Arioka M.
Th e catalytic activity, but not receptor
binding, of sPLA2s plays a critical role
for neurite outgrowth induction in
PC12 cells. Brain Res. 2004;1015(1–
29. Mora R, Valverde B, Díaz C, Lomonte
B, Gutiérrez JM. A Lys49 phospholipase
A2 homologue from Bothrops
asper snake venom induces proliferation,
apoptosis and necrosis in a
lymphoblastoid cell line. Toxicon.
30. J.B. H, T. S-D. Secreted phospholipases
A2 of snake venoms: Eff ects on
the peripheral neuromuscular system
with comments on the role of phospholipases
A2 in disorders of the CNS
and their uses in industry. Toxins (Basel).
This work is licensed under a Creative Commons Attribution 4.0 International License.