Open Access
Research
(Published
online: 19-06-2016)
12.
Human umbilical mesenchymal stem cells
conditioned medium promote primary wound healing regeneration -
Dwi Liliek Kusindarta, Hevi Wihadmadyatami, Yuda Heru Fibrianto,
Widagdo Sri Nugroho, Heru Susetya, Dewi Kania Musana, Hery
Wijayanto, Surya Agus Prihatna and A. E. T. H. Wahyuni
Veterinary World, 9(6): 605-610
doi:
10.14202/vetworld.2016.605-610
Dwi Liliek Kusindarta:
Department of Anatomy, Faculty of Veterinary Medicine,
Universitas Gadjah Mada, Yogyakarta, Indonesia; indarta@ugm.ac.id
Hevi Wihadmadyatami:
Department of Anatomy, Faculty of Veterinary Medicine,
Universitas Gadjah Mada, Yogyakarta, Indonesia;
heviwihadmadyatami@ugm.ac.id
Yuda Heru Fibrianto:
Department of Physiology, Faculty of Veterinary Medicine,
Universitas Gadjah Mada, Yogyakarta, Indonesia; fibrianto1802@gmail.com
Widagdo Sri Nugroho:
Department of Veterinary Public Health, Faculty of Veterinary
Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia;
weesnugroho@ugm.ac.id
Heru Susetya:
Department of Veterinary Public Health, Faculty of Veterinary
Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia;
heruanggikiki@yahoo.com
Dewi Kania Musana:
Department of Anatomy, Faculty of Veterinary Medicine,
Universitas Gadjah Mada, Yogyakarta, Indonesia; musanakd@ugm.ac.id
Hery Wijayanto:
Department of Anatomy, Faculty of Veterinary Medicine,
Universitas Gadjah Mada, Yogyakarta, Indonesia; herykh@ugm.ac.id
Surya Agus Prihatna:
Department of Obstetrics and Gynecology, Faculty of Veterinary
Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia;
prihatno@ugm.ac.id
A. E. T. H. Wahyuni:
Department of Microbiology, Faculty of Veterinary Medicine,
Universitas Gadjah Mada, Yogyakarta, Indonesia; wahyuni_aeth@yahoo.com
Received: 13-12-2015, Accepted: 06-05-2016, Published online:
19-06-2016
Corresponding author:
Dwi Liliek Kusindarta, e-mail: indarta@ugm.ac.id
Citation:
Kusindarta DL, Wihadmadyatami H, Fibrianto YH, Nugroho WS,
Susetya H, Musana DK, Wijayanto H, Prihatna SA, Wahyuni AETH
(2016) Human umbilical mesenchymal stem cells conditioned medium
promote primary wound healing regeneration,
Veterinary World, 9(6):
605-610.
Abstract
Aim:
This research was conducted to clarify the capability of human
umbilical mesenchymal stem cells conditioned medium (HU-MSCM) to
promote regenerations of primary wound healing on the incision
skin injury.
Materials and Methods:
In this study, two approaches
in vitro
and
in vivo
already done. On
in vitro
analysis, tube formation was performed using HU vein endothelial
cells in the presence of HU-MSCM, in some experiments cells line
was incubated prior the presence of lipopolysaccharide and
HU-MSCM then apoptosis assay was performed. Furthermore,
in vivo
experiments 12 female rats (Rattus
norvegicus)
were used after rats anesthetized, 7 mm wound was made by
incision on the left side of the body. The wound was treated
with HU-MSCM containing cream, povidone iodine was run as a
control. Wound healing regenerations on the skin samples were
visualized by hematoxylin-eosin staining.
Results:
In vitro
models elucidate HU-MSCM may decreasing inflammation at the
beginning of wound healing, promote cell migration and
angiogenesis. In addition
in vivo
models show that the incision length on the skin is decreasing
and more smaller, HE staining describe decreasing of
inflammation phase, increasing of angiogenesis, accelerate
fibroplasia, and maturation phase.
Conclusions:
Taken together our observation indicates that HU-MSCM could
promote the acceleration of skin tissue regenerations in primary
wound healing process.
Keywords:
human umbilical mesenchymal stem cells conditioned medium,
regenerations, wound healing.
References
1. Hardy, M.A. (1989) The biology of scar formation. Phys.
Ther., 69(12): 1014-1024.
PMid:2479956 |
|
2. Heureux, N.L. (2000) Stem cell and blood. Mol. Ther., 1,
S83-S106.
http://dx.doi.org/10.1006/mthe.2000.0153 |
|
3. Okita, K., Nagata, N. and Yamanaka, S. (2011)
Immunogenicity of induced pluripotent stem cells. Circ.
Res., 109(7): 720-721.
http://dx.doi.org/10.1161/RES.0b013e318232e187
PMid:21921270 |
|
4. Araki, R., Uda, M., Hoki, Y., Sunayama, M., Nakamura, M.,
Ando, S., Sugiura, M., Ideno, H., Shimada, A., Nifuji, A.
and Abe, M. (2013) Negligible immunogenicity of terminally
differentiated cells derived from induced pluripotent or
embryonic stem cells. Nature, 494(7435): 100-104.
http://dx.doi.org/10.1038/nature11807
PMid:23302801 |
|
5. Tan, Y., Ooi, S. and Wang, L. (2014) Immunogenicity and
tumorigenicity of pluripotent stem cells and their
derivatives: Genetic and epigenetic perspectives. Curr. Stem
Cell Res. Ther., 9(1): 63-72.
http://dx.doi.org/10.2174/1574888X113086660068
PMid:24160683 PMCid:PMC3873036 |
|
6. Wei, X., Yang, X., Han, Z., Qu, F., Shao, L. and Shi, Y.
(2013) Mesenchymal stem cells: A new trend for cell therapy.
Acta Pharmacol. Sin., 34(6): 747-754.
http://dx.doi.org/10.1038/aps.2013.50
PMid:23736003 PMCid:PMC4002895 |
|
7. Christopeit, M., Schendel, M., Föll, J., Müller, L.P.,
Keysser, G. and Behre, G. (2008) Marked improvement of
severe progressive systemic sclerosis after transplantation
of mesenchymal stem cells from an allogeneic
haploidentical-related donor mediated by ligation of CD137L.
Leukemia, 22(5): 1062-1064.
http://dx.doi.org/10.1038/sj.leu.2404996
PMid:17972956 |
|
8. Dominici, M., Le Blanc, K., Mueller, I.,
Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R.J.,
Keating, A., Prockop, D.J. and Horwitz, E.M. (2006) Minimal
criteria for defining multipotent mesenchymal stromal cells.
The international society for cellular therapy position
statement. Cytotherapy, 8(4): 315-317.
http://dx.doi.org/10.1080/14653240600855905
PMid:16923606 |
|
9. Kim, H.O., Choi, S.M. and Kim, H.S. (2013) Mesenchymal
stem cell-derived secretome and microvesicles as a cell-free
therapeutics for neurodegenerative disorders. Tissue Eng.
Regen. Med., 10(3): 93-101.
http://dx.doi.org/10.1007/s13770-013-0010-7 |
|
10. Baglio, S.R., Pegtel, D.M. and Baldini, N. (2012)
Mesenchymal stem cell secreted vesicles provide novel
opportunities in (stem) cell-free therapy. Front Physiol.,
3: 1-11.
http://dx.doi.org/10.3389/fphys.2012.00359
PMid:22973239 PMCid:PMC3434369 |
|
11. Fukuoka, H., Suga, H., Narita, K., Watanabe, R. and
Shintani, S. (2012) The latest advance in hair regeneration
therapy using proteins secreted by adipose-derived stem
cells. Am. J. Cosmet. Surg., 29(4): 273-282.
http://dx.doi.org/10.5992/AJCS-D-12-00015.1 |
|
12. Zhou, B.R., Xu, Y., Xu, Y., Guo, S.L., Wang, Y., Zhu,
F., Permatasari, F., Wu, D., Yin, Z. and Luo, D. (2013) The
effect of conditioned media of adipose-derived stem cells on
wound healing after ablative fractional carbon dioxide laser
resurfacing. Biomed. Res Int., 2013: 519126.
http://dx.doi.org/10.1155/2013/519126
PMid:24381938 PMCid:PMC3867954 |
|
13. Park, B.S., Kim, W.S., Choi, J.S., Kim, H.K., Won, J.H.,
Ohkubo, F. and Fukuoka, H. (2010) Hair growth stimulated by
conditioned medium of adipose-derived stem cells is enhanced
by hypoxia: Evidence of increased growth factor secretion.
Biomed. Res., 31(1): 27-34.
http://dx.doi.org/10.2220/biomedres.31.27 |
|
14. Hwang, J. and Weiss, R.E. (2014) Steroid-induced
diabetes: A clinical and molecular approach to understanding
and treatment. Diabetes Metab. Res. Rev., (30): 96-102.
http://dx.doi.org/10.1002/dmrr.2486
PMid:24123849 PMCid:PMC4112077 |
|
15. Di Santo, S., Yang, Z., von Ballmoos, M.W., Voelzmann,
J., Diehm. N., Baumgartner, I. and Kalka, C. (2009) Novel
cell-free strategy for therapeutic angiogenesis: In vitro
generated conditioned medium can replace progenitor cell
transplantation. PLoS One, 4(5): e5643.
http://dx.doi.org/10.1371/journal.pone.0005643 |
|
16. Teodelinda, M., Michele, C., Sebastiano, C., Ranieri, C.
and Chiara, G. (2011) Amniotic liquid derived stem cells as
reservoir of secreted angiogenic factors capable of
stimulating neo-arteriogenesis in an ischemic model.
Biomaterials, 32(15): 3689-3699.
http://dx.doi.org/10.1016/j.biomaterials.2011.01.071
PMid:21371750 |
|
17. Wihadmadyatami, H., Röder, L., Berghöfer, H., Bein, G.,
Heidinger, K., Sachs, U.J. And Santoso, S. (2016)
Immunisation against αIIbβ3 and αvβ3 in a Type 1 variant of
Glanzmann's thrombasthenia caused by a missense mutation
Gly540Asp on β3. Thromb. Haemost., 116(2).
http://dx.doi.org/10.1160/TH15-12-0982
PMid:27098940 |
|
18. Brooks, P.C., Montgomery, A.M.P., Rosenfeld, M.,
Reisfeld, R.A., Hu, T.H., Klier, G. and Cheresh, D.A. (1994)
Integrin avb3 antagonists promote tumor-regression by
inducing apoptosis of angiogenic blood-vessels. Cell, 79(7):
1157-1164.
http://dx.doi.org/10.1016/0092-8674(94)90007-8 |
|
19. Pawitan, J.A. (2014) Prospect of stem cell conditioned
medium in regenerative medicine. Biomed. Res. Int., 2014:
965849.
http://dx.doi.org/10.1155/2014/965849
PMid:25530971 PMCid:PMC4229962 |
|
20. Velnar, T., Bailey, T. and Smrkolj, V. (2009) The wound
healing process: an overview of the cellular and molecular
mechanisms. J. Int. Med. Res., 37(5): 1528-1542.
http://dx.doi.org/10.1177/147323000903700531 |
|
21. Mutsaers, S.E., Laurent, G.J., Bishop, E. and
Mcgrouther, G. (1997) Mechanisms of Tissue Repair: From
Wound Healing to Fibrosis. Int. J. Biochem. Cell Biol.,
29(1): 5-17.
http://dx.doi.org/10.1016/S1357-2725(96)00115-X |
|
22. Brooks, P.C., Clarck, R.A.F. and Cheresh, D.A. (1994)
Requirement of vascular integrin avb3 for angiogenesis.
Science, 264(5158):569-571.
http://dx.doi.org/10.1126/science.7512751
PMid:7512751 |
|
23. Horton, M A. (1997) The alpha v beta 3 integrin
vitronectin receptor. Int. J. Biochem. Cell Biol., 29(5):
721-725.
http://dx.doi.org/10.1016/S1357-2725(96)00155-0 |
|
24. Aggarwal, S. and Pittenger, M.F. (2009) Human
mesenchymal stem cells modulate allogeneic immune cell
responses. Transplantation, 105(4): 1815-1822. |
|
25. Singer, N.G. and Caplan, A.I. (2011) Mesenchymal stem
cells: Mechanisms of inflammation. Annu. Rev. Pathol., 6:
457-478.
http://dx.doi.org/10.1146/annurev-pathol-011110-130230
PMid:21073342 |
|
26. Zheng, Z.H., Li, X.Y., Ding, J., Jia, J.F. and Zhu, P.
(2008) Allogeneic mesenchymal stem cell and mesenchymal stem
cell-differentiated chondrocyte suppress the responses of
Type II collagen-reactive T cells in rheumatoid arthritis.
Rheumatology, 47(1): 22-30.
http://dx.doi.org/10.1093/rheumatology/kem284
PMid:18077486 |
|
27. Wu, Y.S. and Chen, S.N. (2014) Apoptotic cell: Linkage
of inflammation and wound healing. Front Pharmacol., 5: 1-6.
http://dx.doi.org/10.3389/fphar.2014.00001
PMid:24478702 PMCid:PMC3896898 |
|
28. Desmoulière, A., Badid, C., Bochaton-Piallat, M.L. and
Gabbiani, G. (1997) Apoptosis during wound healing,
fibrocontractive diseases and vascular wall injury. Int. J.
Biochem. Cell Biol., 29(1): 19-30.
http://dx.doi.org/10.1016/S1357-2725(96)00117-3 |
|
29. Branski, L.K., Gauglitz, G.G., Herndon, D.N. and Jeschke,
M.G. (2009) A review of gene and stem cell therapy in
cutaneous wound healing. Burns, 35(2): 171-180.
http://dx.doi.org/10.1016/j.burns.2008.03.009
PMid:18603379 PMCid:PMC3899575 |
|
30. Chen, L., Tredget, E.E., Wu, P.Y.G., Wu, Y. and Wu, Y.
(2008) Paracrine factors of mesenchymal stem cells recruit
macrophages and endothelial lineage cells and enhance wound
healing. PLoS One, 3(4): e1886.
http://dx.doi.org/10.1371/journal.pone.0001886 |
|
31. Kim, W.S., Park, B.S., Sung, J.H., Yang, J.M., Park,
S.B., Kwak, S.J. and Park, J.S. (2007) Wound healing effect
of adipose-derived stem cells: A critical role of secretory
factors on human dermal fibroblasts. J. Dermatol. Sci.,
48(1): 15-24.
http://dx.doi.org/10.1016/j.jdermsci.2007.05.018
PMid:17643966 |
|
32. Singer, J.A. and Clark, R.A.F. (1999) Cutaneus wound
healing. N. Engl. J. Med., 341: 738-746.
http://dx.doi.org/10.1056/NEJM199909023411006
PMid:10471461 |
|