Volume 25, Issue 5 (9-2021)                   ibj 2021, 25(5): 334-342 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Habibi M, Chehelcheraghii F. The Effect of Bone Marrow Mesenchymal Stem Cell Sheets on Skin Capillary Parameters in a diabetic wound model: A Novel Preliminary Study. ibj. 2021; 25 (5) :334-342
URL: http://ibj.pasteur.ac.ir/article-1-3262-en.html
Background: Treatment with bone marrow mesenchymal stem cell (BMMSCs) has anti-inflammatory, tissue regenerative, angiogenic, and immune-stimulating effects. When using as sheets or accumulate, BMMSCs causes the development of neoangiogenesis in damaged skin tissue. Diabetes, a metabolic disorder, can negatively affect many physiological functions, including the process of skin injury repair. This adverse impact may increase the risk of skin surgery. Random skin flap (RSF) is commonly used in reconstructive surgery. The terminal part of the RSF is often affected by necrosis because of impaired blood flow, which is exacerbated in diabetes. This study investigated the effect of stem cells, applied as accumulated or cell sheets, along with RSF surgery on skin capillaries in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty male Wistar rats were divided into three groups (n = 10): diabetes-RSF control, diabetes-RSF local applied stem cells (loc-BMMSCs), diabetes-RSF applied stem cells as accumulated or cell sheets (ac-BMMSCs). Two weeks after the STZ injection, RSF surgery and stem cell therapy (6 × 109) were carried out (day zero). Furthermore, stereological methods were used to investigate the capillary patterns among the groups. Anti-CD31/platelet endothelial cell adhesion molecule-1 immunohistochemistry was also used for further confirmation of changes in capillary parameters. Results: The results demonstrated that capillaries were protected by MSC sheets in the flap tissue, and the thickness of the epidermal layer was improved, indicationg the possible beneficial effects of MSC sheets on diabetic wound treatment. Conclusion: Stem cells, as ac-BMMSCs, may decrease the levels of wound healing complications in diabetes and can be considered as a cell therapy option in such conditions. 

1. 1. Berlanga-Acosta J, López-Mola E, Garcia-Siverio M, Guillén-Nieto G, López-Saura P, Valdez-Pérez C, Puentes-Madera I, Savigne-Gutierrez W, Álvarez-Duarte H, Miranda-Espinosa N. Detrimental impact of acute and chronic glucose burden in wound-healing cells: fibroblasts, myofibroblasts and vascular precursor cells. Biotecnología aplicada journal 2012; 29(4): 208-217.
2. Zhao L, Lu J, Wang C, Zhao W, Qing E, Ma J. Prostaglandin E1 increases the blood flow rate of saphenous vein grafts in patients undergoing off-pump coronary artery bypass grafting. Journal of cardiothoracic and vascular anesthesia 2013; 27(6): 1208-1211. [DOI:10.1053/j.jvca.2013.07.001]
3. Kiumehr S, Demehri S, Rabbani S, Amanpour S, Mohagheghi MA, Dehpour AR. Preconditioning of the rat random-pattern skin flap: modulation by opioids. British journal of plastic surgery 2005; 58(1): 58-64. [DOI:10.1016/j.bjps.2004.06.001]
4. Miyawaki T, Jackson IT, Bier UC, Andrus L, Williams F, Bradford M. The effect of capsaicin ointment on skin for the survival of a cutaneous flap. European journal of plastic surgery 2001; 24(1): 28-30. [DOI:10.1007/s002380000221]
5. Gurunluoglu R, Ozer K, Skugor B, Lubiatowski P, Carnevale K, Siemionow M. Effect of transfection time on the survival of epigastric skin flaps pretreated with adenovirus encoding the VEGF gene. Annals of plastic surgery 2002; 49(2): 161-169. [DOI:10.1097/00000637-200208000-00009]
6. Raval Z, Losordo DW. Cell therapy of peripheral arterial disease: from experimental findings to clinical trials. Circulation research 2013; 112(9): 1288-1302. [DOI:10.1161/CIRCRESAHA.113.300565]
7. Boyce ST, Lalley AL. Tissue engineering of skin and regenerative medicine for wound care. Burns and trauma 2018; 6(1): 4. [DOI:10.1186/s41038-017-0103-y]
8. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109(12): 1543-1549. [DOI:10.1161/01.CIR.0000124062.31102.57]
9. Wang T, Tang W, Sun S, Wan Z, Xu T, Huang Z, Weil MH. Mesenchymal stem cells improve outcomes of cardiopulmonary resuscitation in myocardial infarcted rats. Journal of molecular and cellular cardiology 2009; 46(3): 378-384. [DOI:10.1016/j.yjmcc.2008.11.014]
10. Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D, Shimizu H. Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. The journal of immunology 2008; 180(4): 2581-2587. [DOI:10.4049/jimmunol.180.4.2581]
11. Lee DW, Jeon YR, Cho EJ, Kang JH, Lew DH. Optimal administration routes for adipose‐derived stem cells therapy in ischaemic flaps. Journal of tissue engineering and regenerative medicine 2014; 8(8): 596-603. [DOI:10.1002/term.1552]
12. Uysal AC, Mizuno H, Tobita M, Ogawa R, Hyakusoku H. The effect of adipose-derived stem cells on ischemia-reperfusion injury: immunohistochemical and ultrastructural evaluation. Plastic and reconstructive surgery 2009; 124(3): 804-815. [DOI:10.1097/PRS.0b013e3181b17bb4]
13. Yanagawa B, Kataoka M, Ohnishi S, Kodama M, Tanaka K, Miyahara Y, Ishibashi-Ueda H, Aizawa Y, Kangawa K, Nagaya N. Infusion of adrenomedullin improves acute myocarditis via attenuation of myocardial inflammation and edema. Cardiovascular research 2007; 76(1): 110-118. [DOI:10.1016/j.cardiores.2007.05.027]
14. Lin YD, Yeh ML, Yang YJ, Tsai DC, Chu TY, Shih YY, Chang MY, Liu YW, Tang ACL, Chen TY. Intramyocardial peptide nanofiber injection improves postinfarction ventricular remodeling and efficacy of bone marrow cell therapy in pigs. Circulation 2010; 122(11suppl): S132-S141. [DOI:10.1161/CIRCULATIONAHA.110.939512]
15. Li M, Ma J, Gao Y, Yang L. Cell sheet technology: a promising strategy in regenerative medicine. Cytotherapy 2019; 21(1): 3-16. [DOI:10.1016/j.jcyt.2018.10.013]
16. Moschouris K, Firoozi N, Kang Y. The application of cell sheet engineering in the vascularization of tissue regeneration. Regenerative medicine 2016; 11(6): 559-570. [DOI:10.2217/rme-2016-0059]
17. Heinrich AC, Patel SA, Reddy BY, Milton R, Rameshwar P. Multi-and inter-disciplinary science in personalized delivery of stem cells for tissue repair. Current stem cell research and therapy 2009; 4(1): 16-22. [DOI:10.2174/157488809787169075]
18. Korff T, Augustin HG. Integration of endothelial cells in multicellular spheroids prevents apoptosis and induces differentiation. journal of cell biology 1998; 143(5): 1341-1352. [DOI:10.1083/jcb.143.5.1341]
19. Jain RK, Au P, Tam J, Duda DG, Fukumura D. Engineering vascularized tissue. Nature biotechnology 2005; 23(7): 821-823. [DOI:10.1038/nbt0705-821]
20. Chen L, Xing Q, Zhai Q, Tahtinen M, Zhou F, Chen L, Xu Y, Qi S, Zhao F. Pre-vascularization enhances therapeutic effects of human mesenchymal stem cell sheets in full thickness skin wound repair. Theranostics 2017; 7(1): 117. [DOI:10.7150/thno.17031]
21. He X, Dong Z, Cao Y, Wang H, Liu S, Liao L, Jin Y, Yuan L, Li B. MSC-derived exosome promotes M2 polarization and enhances cutaneous wound healing. Stem cells international 2019; 2019: 7132708. [DOI:10.1155/2019/7132708]
22. Rezazadeh K, Chehelcheraghi F, Anbari K. The effect of bone marrow derived mesenchymal stem cells on the survival of random skin flap on sterptozotocin-induced diabetic rats. Journal of advances in medical and biomedical research 2018; 26(119): 24-33. [DOI:10.30699/jambs.26.119.24]
23. Sekine H, Shimizu T, Matsuura K, Yamato M, Takahashi M, Murakami T, Kobayashi EK, Hagiwara N, Okano T. Cell sheet transplantation improves damaged heart function via more cell survival in comparison with dissociated cell injection. Circulation 2009; 120(suppl 18): Abstract 3697.
24. Wu Y, Chen L, Scott PG, Tredget EE. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem cells 2007; 25(10): 2648-2659. [DOI:10.1634/stemcells.2007-0226]
25. Sui BD, Hu CH, Liu AQ, Zheng CX, Xuan K, Jin Y. Stem cell-based bone regeneration in diseased microenvironments: challenges and solutions. Biomaterials 2019; 196: 18-30. [DOI:10.1016/j.biomaterials.2017.10.046]
26. Chai J, Ge J, Zou J. Effect of autologous platelet-rich plasma gel on skin flap survival. Medical science monitor 2019; 25: 1611-1620. [DOI:10.12659/MSM.913115]
27. Alex JC, Bhattacharyya TK, Smyrniotis G, O'Grady K, Konior RJ, Toriumi DM. A histologic analysis of three‐dimensional versus two‐dimensional tissue expansion in the porcine model. Laryngoscope 2001; 111(1): 36-43. [DOI:10.1097/00005537-200101000-00007]
28. Howard CV, Cruz‐Orive LM, Yaegashi H. Estimating neuron dendritic length in 3D from total vertical projections and from vertical slices. Acta neurologica scandinavica 1992; 137: 14-19. [DOI:10.1111/j.1600-0404.1992.tb05033.x]
29. Wobser M, Siedel C, Schrama D, Bröcker EB, Becker JC, Vetter-Kauczok CS. Expression pattern of the lymphatic and vascular markers VEGFR-3 and CD31 does not predict regional lymph node metastasis in cutaneous melanom. Archives of dermatological research 2006; 297(8): 352-357. [DOI:10.1007/s00403-005-0633-1]
30. Mendis KR, Balaratnasingam C, Yu P, Barry CJ, McAllister IL, Cringle SJ, Yu DY. Correlation of histologic and clinical images to determine the diagnostic value of fluorescein angiography for studying retinal capillary detail. Investigative ophthalmology and visual science 2010; 51(11): 5864-5869. [DOI:10.1167/iovs.10-5333]
31. Mathieu C, Chevrier A, Lascau-Coman V, Rivard GE, Hoemann CD. Stereological analysis of subchondral angiogenesis induced by chitosan and coagulation factors in microdrilled articular cartilage defects. Osteoarthritis and cartilage 2013; 21(6): 849-859. [DOI:10.1016/j.joca.2013.03.012]
32. Sridharan G, Shankar AA. Toluidine blue: a review of its chemistry and clinical utility. Journal of oral and maxillofacial pathology 2012; 16(2): 251-525. [DOI:10.4103/0973-029X.99081]
33. Barrientos S, Stojadinovic O, Golinko Ms, Brem H, Tomic‐Canic M. Growth factors and cytokines in wound healing. Wound repair and regeneration 2008; 16(5): 585-601. [DOI:10.1111/j.1524-475X.2008.00410.x]
34. Yeum CE, Park EY, Lee SB, Chun HJ, Chae GT. Quantification of MSCs involved in wound healing: use of SIS to transfer MSCs to wound site and quantification of MSCs involved in skin wound healing. Journal of tissue engineering and regenerative medicine 2013; 7(4): 279-291. [DOI:10.1002/term.521]
35. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nature medicine 2005; 11(4): 367. [DOI:10.1038/nm0405-367]
36. Xue W, Mizukami I, Todd RF, Petty HR. Urokinase-type plasminogen activator receptors associate with β1 and β3 integrins of fibrosarcoma cells: dependence on extracellular matrix components. Cancer research 1997, 57(9): 1682-1689.
37. Gerber H-P, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. Journal of biological chemistry 1998; 273(21): 13313-13316. [DOI:10.1074/jbc.273.21.13313]
38. Jiao J, Milwid JM, Yarmush ML, Parekkadan B. A mesenchymal stem cell potency assay. Methods in molcular biology 2011; 677: 221-231. [DOI:10.1007/978-1-60761-869-0_16]
39. Badiavas EV, Abedi M, Butmarc J, Falanga V, Quesenberry P. Participation of bone marrow derived cells in cutaneous wound healing. Journal of cellular physiology 2003; 196(2): 245-250. [DOI:10.1002/jcp.10260]
40. Najar M, Rouas R, Raicevic G, Boufker HI, Lewalle P, Meuleman N, Bron D, Toungouz M, Martiat P, Lagneaux L. Mesenchymal stromal cells promote or suppress the proliferation of T lymphocytes from cord blood and peripheral blood: the importance of low cell ratio and role of interleukin-6. Cytotherapy 2009; 11(5): 570-583. [DOI:10.1080/14653240903079377]
41. Nakatani D, Sato H, Sakata Y, Shiotani I, Kinjo K, Mizuno H, Shimizu M, Ito H, Koretsune Y, Hirayama A. Influence of serotonin transporter gene polymorphism on depressive symptoms and new cardiac events after acute myocardial infarction. American heart journal 2005; 150(4): 652-658. [DOI:10.1016/j.ahj.2005.03.062]
42. Rennert RC, Sorkin M, Januszyk M, Duscher D, Kosaraju R, Chung MT, Lennon J, Radiya-Dixit A, Raghvendra S, Maan ZN, Hu MS, Rajadas J, Rodrigues M, Gurtner GC. Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations. Stem cell research and therapy 2014; 5(3): 79. [DOI:10.1186/scrt468]
43. Kuo YR, Wang CT, Cheng JT, Wang FS, Chiang YC, Wang CJ. Bone marrow-derived mesenchymal stem cells enhanced diabetic wound healing through recruitment of tissue regeneration in a rat model of streptozotocin-induced diabetes. Plastic and reconstructive surgery 2011; 128(4): 872-880. [DOI:10.1097/PRS.0b013e3182174329]

Add your comments about this article : Your username or Email:

Send email to the article author

© 2021 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb