Effects of PBMC and Combined-PBMC with BM-MSCs to the Expression of α2β1 Integrin Level on Full Thickness Rat’ Burn Skin

  • Gusti Revilla Department of Anatomy, Faculty of Medicine, Andalas University. Jl. Proklamasi Kemerdekaan No.94 PO BOX 49 Padang, 25127, West Sumatra, Indonesia
  • Eryati Darwin Department of Histology, Faculty of Medicine, Andalas University. Jl. Proklamasi Kemerdekaan No.94 PO BOX 49 Padang, 25127, West Sumatra, Indonesia
  • Fedik A. Rantam Department of Microbiology Veterinary Medicine Faculty and Stem cell Laboratory, Institute of Tropical Disease (ITD), Faculty of Medicine, Airlangga University, 60115, Surabaya, Indonesia
  • Yanwirasti Yanwirasti Department of Anatomy, Faculty of Medicine, Andalas University. Jl. Proklamasi Kemerdekaan No.94 PO BOX 49 Padang, 25127, West Sumatra, Indonesia
Keywords: PBMC, BM-MSC, integrin- α2β1, wound healing.

Abstract

Bone marrow mesenchymal stem cells (BM-MSCs) increases the percentage of integrin α2β1 expression on rat’ wound healing process, but the study which is related to PBMC (peripheral blood mononuclear cell) and PBMC combined with BM-MSCs towards burn healing process has not been conducted yet. The aim of the study was to determine the expression of integrin α2β1 as a result of PBMC and PBMC combined to BM-MSCs administrations towards rat’ wound healing process. Experimental research with the post test only control design was conducted on 12 Wistar rats, divided into three experimental groups: PBS (Phosphate Buffer Saline) as control group, PBMC, and PBMC combined with BM-MSCs. Stem cells were subcutaneously injected with 2x106 cells/ml. A full-thickness burn was made on the dorsal side (back). Skin tissues were collected to investigate the expression of integrin α2β1 using immunohistochemistry method on day-14.Administration of only PBMC (2.972), and PBMC combined with BM-BSCs (3.297) elevated the percentage of integrin α2β1 compared with control group (2.340), but significant result was only in combination group (p=0,05). The administration of only PBMC and PBMC combined with BM-MSCs elevated the expression of integrin α2β1, which showed that both of stem cells accelerated the migration of keratinocyts that will expedite the re-epithelialization phase in burn wound healing.

References

. R. Abe , SC. Donnelly, T Peng, R. Bucala, CN. Metz. 2001. “Peripheral blood fibrocytes: differentiation pathway and migration to wound sites.”. J Immunol. [On- line]. 166, pp.7556-62. Available: www.ncbi.nlm.nih.gov/ pubmed/ 11390511[May. 24, 2016]

. CR. Kleiveland. “Peripheral blood mononuclear cells.” in The impact of food bioactives on health.Verhoeckx K. et al. (eds). Springer, Cham, 2015, pp.161-167

. MF. Pittenger, AM Mackay, SC. Beck, RK. Jaiswal, R. Douglas, JD. Mosca, MA. Moorman, DW. Simonetti, S. Craig, DR. Marshak. 1996. “Multilineage potential of adult human mesenchymal stem cells.” [On- line]. Science. [On- line]. 284,pp.143-7. Available: www.ncbi.nlm.nih.gov/pubmed/10102814 [Apr. 05, 2016]

. G. Roshanak, Z. Dimitra, L. Hongzhe, CL. Hooi, S. Shamit & S. Stefan. 2017. “Human primary bone marrow mesenchymal stromal cells and their in vitro progenies display distinct transcriptional profile signatures.” Scientific Reports, [On- line]. 7(10338). doi:10.1038/s41598-017-09449-x. Available: https://www.nature. com/articles/s41598-017-09449-x [Jan. 12, 2018]

. G. Revilla, E. Darwin, Yanwirasti, FA. Rantam. 2016. “Effect of allogeneic bone marrow-mesenchymal stem cells (bm-mscs) to accelerate burn healing of rat on the expression of collagen type I and integrin α2β1.” Pak J Biol Sci, [On- line]. 19(8-9),pp.345-351. doi: 10.3923/pjbs.2016.345.351. Available: www.ncbi.nlm.nih.gov/ pubmed/29023021 [Apr. 05, 2016]

. G. Revilla, E. Darwin, Yanwirasti, and FA. Rantam. “Effects of peripheral blood mononuclear cells (PBMC) to the expression of type-1 collagen in rat burns,” presented at the 4th Scientific Consortium. Annual meeting of hypoxia and oxidative stress studies, Jakarta, 2014.

. H. Jian, C. Ming, Q. Lijun, W. Junhong, G. Yan, and X. Di. 2017. “Fibrillar type I collagen enhances the differentiation and proliferation of myofibroblasts by lowering α2β1 2017integrin expression in cardiac fibrosis.” Biomed Res Int, [On- line] 1790808. doi: 10.1155/2017/1790808. Available: www.hindawi. com/journals/bmri/2017/1790808/ [Jan. 12, 2018]

. M. Sasaki, R. Abe, Y. Fujita, S. Ando, D. Inokuma, H. Shimizu. 2008. “Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by trans-differentiation into multiple skin cell type.” J Immunol, [On- line] 180,pp.2581-7. PMID: 18250469. Available: www.ncbi.nlm.nih.gov/pubmed/18250469 [Apr. 05, 2016]

. BJ. Herdrich, RC. Lind, KW. Liechty. 2008. “Multipotent adult progenitor cells: their role in wound healing and the treatment of dermal wounds.” Cytotherapy, [On- line] 10,pp.543-50. doi: 10.1080/14653240802345820. Available:/www.ncbi.nlm.nih.gov/pubmed/18836914 [Apr. 05, 2016]

. Medina, RT. Kilani, N. Carr, E. Brown, A. Ghahary. 2007. “Transdifferentiation of peripheral blood mononuclear cells into epithelial-like cells.” Am J Pathol, [On- line] 171,pp1140–1152. doi: 10.2353/ajpath.2007.070051. Available: www.ncbi.nlm.nih.gov/pubmed/17717137 [Apr. 05, 2016]

. EK. Moioli, PA. Clark, M. Chen, JE. Dennis, HP. Erickson, SL. Gerson, et al. 2008. “Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues.” PLoS ONE, [On- line] 3:e3922. https://doi.org/10.1371/ journal. pone.0003922. Available: journals.plos.org/plosone/ article?id=10.1371/journal.pone.0003922[Apr. 05, 2016]

. WHO. “Burns.” http://www.who.int/news-room/fact-sheets/detail/burns, March, 6, 2018 [June, 7, 2018].

. AK. Vern, BA. Latenser. “Specimen collection and analysis,” in Burns Wound Healing. DiPietro, Luisa A, L. Aime. (eds). Vol.78. Totowa: Humana Press, 2003,pp.241-254.

. HP. Lorenz, MT. Longaker. “Wounds: biology, pathology, and management,” in Surgery: Norton J.A. et al. (eds), New York: Springer, 2008,pp.77-88.

. K. Kotowicz, GL. Dixon, NJ. Klein, MJ. Peters, RE. Callard. 2000. “Biological function of CD40 on human endothelial cells: costimulation with CD40 ligand and interleukin-4 selectively induces expression of vascular cell adhesion molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes.” Immunology, [On- line], 100,pp.441-8. Available: www.ncbi.nlm.nih.gov/pubmed/10929070 [Apr. 05, 2016]

. J. Xupin, T. Miao, G. Xiaowei, Z. Dongxia, Z. Qiong, Z. Jiaping, H. Yuesheng. 2014. “Switch from avb5 to avb6 integrin is required for CD9-regulated keratinocyte migration and MMP-9 activation.: FEBS Letters, [On- line], 588 (2014),pp.4044–4052. http://dx.doi.org/10.1016/j.febslet.2014.09.027. Available: febs.onlinelibrary. wiley.com/doi/pdf/10.1016/j.febslet.2014.09.027 [Apr. 05, 2016]

. F. Decline, P. Rousselle. 2001. “Keratinocyte migration requires alpha2beta1 integrin-mediated interaction with the laminin 5 gamma2 chain.” J Cell Sci. [On- line], 114,pp.811-23. PMID: 11171386. Available: www.ncbi. nlm.nih.gov/pubmed/11171386 [Apr. 05, 2016]

. VA. Paramonov, VY. Chebotarev. 2002. “Modeling of thermal skin injury for the development of local treatment drugs.” Bull Exp Biol Med, [On- line] 134,pp.512-515. PMID: 12802465. Available: www.ncbi. nlm.nih.gov/pubmed/12802465[Apr. 05, 2016]

. ZG. Zhang, I. Bothe, F. Hirche, M. Zweers et al. 2006. “Interactions of primary fibroblasts and keratinocytes with extracellular matrix proteins: contribution of α2 β1 integrin.” Journal of Cell Science, [On- line] 119,pp.1886-1895. doi: 10.1242/jcs.02921. Available: jcs.biologists.org/content/119/9/1886 [Apr. 05, 2016]

. Z. Jun, H. Xiaowen, W. Haijun, L. Xiaoyan, Z. Tao, W. Yunchuan, and H. Dahai. 2015. “The challenges and promises of allogeneic mesenchymal stem cells for use as a cell-based therapy.” Stem Cell Res Ther. [On- line], 15(6),pp.234. doi: 10.1186/s13287-015-0240-9. Available: www.ncbi.nlm.nih.gov/pmc/articles/PMC4665863/ [Apr. 05, 2016]

. JA. Semon, LH. Nagy, CB. Llamas, HA. Tucker, RH. Lee, DJ. Prockop. 2010. “Integrin expression and integrin-mediated adhesion in vitro of human multipotent stromal cells (MSCs) to endothelial cells from various blood vessels.” Cell Tissue Res, [On- line], 341,pp.147-58. doi: 10.1007/s00441-010-0994-4. Available: www.ncbi.nlm.nih.gov/pubmed/20563599 [Apr. 05, 2016]

. EF. Srour, A. Jetmore, FM. Wolber, PA. Plett, R. Abonour, MC. Yoder, CM. Orschell-Traycoff. 2001. “Homing, cell cycle kinetics and fate of transplanted hematopoietic stem cells.” Leukemia, [On- line], 15,pp.1681-4. PMID: 11681406. Available: www.ncbi.nlm.nih.gov/pubmed/11681406[Apr. 05, 2016]

. FM. Watt. 2002. “Role of integrins in regulating epidermal adhesion, growth and differentiation.” EMBO J. [On- line], 21,pp.3919-26. doi: 10.1093/emboj/cdf399. Available: www.ncbi.nlm.nih.gov/pubmed/12145193 ` [Apr. 05, 2016]

. R. Tamma and D. Ribatti. 2017. “Bone niches, hematopoietic stem cells, and vessel formation.” Int J Mol Sci, [On- line], 18,pp.151. doi: 10.3390/ijms18010151. Available: www.ncbi.nlm.nih.gov/pubmed/28098778 [June, 7, 2018].

. P. Irenaar, S. Olivera, C. Natalie, Yin, R. Horacio, G. Aron, Nusbaum, S. Andrew, B. Shailee, Patel, K. Laiqua, R. Rivkah, Isseroff, and M. Tomic-Canic. 2014. “Epithelialization in wound healing: a comprehensive review.” Adv Wound Care (New Rochelle) [On- line]. 3(7),pp. 445–464. doi: 10.1089/wound.2013.0473. Available: www.ncbi.nlm.nih.gov/pubmed/25032064[Apr. 05, 2016]

. DT. Woodley, A. Wysong, B. DeClerck, M. Chen, and W. Li. 2015. “Keratinocyte migration and a hypothetical new role for extracellular heat shock protein 90 alpha in orchestrating skin wound healing.” Adv Wound Care (New Rochelle), [On- line], 4(4),pp.203–212. doi: 10.1089/wound.2014.0566. Available: www.ncbi.nlm. nih.gov/pmc/articles/PMC4397998/[Apr. 05, 2016]

. LE. Reynolds, FJ. Conti, M. Lucas, R. Grose, S. Robinson, M. Stone, G. Saunders, C. Dickson, RO. Hynes, A. Lacy-Hulbert, K. Hodivala-Dilke. 2005. “Accelerated re-epithelialization in beta3-integrin-deficient-mice is associated with enhanced TGF-beta1 signaling.” Nat Med, [On- line], 11,pp.167-74. doi: 10.1038/nm1165. Available: www.ncbi.nlm.nih.gov/pubmed/15654327[Apr. 05, 2016]

. B. Steffensen, L. Häkkinen, H. Larjava. 2001. “Proteolytic events of wound-healing--coordinated interactions among matrix metalloproteinases (MMPs), integrins, and extracellular matrix molecules.” Crit Rev Oral Biol Med, [On- line], 12,pp.373-98. PMID: 12002821. Available: www.ncbi.nlm.nih.gov/pubmed/12002821[Apr. 05, 2016]

. L. Koivisto, J. Heino, L. Häkkinen, and H. Larjava. 2014. “Integrins in Wound Healing.” Adv Wound Care (New Rochelle), [On- line], 3(12),pp.762–783. doi: 10.1089/wound.2013.0436. Available: www.ncbi.nlm.nih. gov/pubmed/25493210[Apr. 05, 2016]

. G. Revilla, E. Darwin, Yanwirasti and FA. Rantam. 2015. “The therapy of burn healing in Rat (Wistar) by using the combination of peripheral blood mononuclear cells (PBMC) and bone marrow BM-derived mesenchymal stem cell.” African Journal of Internal Medicine, [On- line], 3,pp.162-167. ISSN: 2326-7283. Available: internationalscholarsjournals.org/download.php?id=827856401189940565.pdf&type=application/pdf&op=1[Apr. 05, 2016]

. T. Tsuji. 2004. “Physiological and pathological role of α3β1 integrin.” The Journal of Membrane Biology, [On- line], 200,pp.115-132. Available: link.springer.com/article/10.1007/s00232-004-0696-5[Apr. 05, 2016]

Published
2018-10-06
Section
Articles